RxPG News : Memory

Enriched environment as a child helps reverse memory problem

Tue, 03 Feb 2009 22:52:27 PST

( from http://www.rxpgnews.com ) A new study by researchers from Rush University Medical Center and Tufts University School of Medicine using mice indicate that a child's memory and the severity of learning disorders may be affected by what his or her mother did when she was a child.

Findings from the study are published in the February 4th issue of The Journal of Neuroscience.

Neuroscience researchers studied the brain function of pre-adolescent mice that have a genetically-created defect in memory. When these young mice were given an enriched environment, which is exposure to stimulatory objects, enhanced social interaction and voluntary exercise for two weeks, the memory defect, caused by inhibiting the formation of Ras-GRF1 and Ras-GRF2 proteins, was reversed.

After a few months, the same mice were fertilized and they gave birth to offspring that had the same genetic mutation. However, the offspring had no indications of the memory defect even though the offspring were never exposed to an enriched environment like their mothers.

Previous research in mouse models has shown that early exposure to an enriched environment while pregnant can also positively affect offspring.

"What is so unique about this study is that we provided an enriched environment during pre-adolescence, months before the mice became pregnant, yet the beneficial effect reached into the next generation," said Dean Hartley, PhD, neuroscience researcher at Rush University Medical Center and study co-investigator. "The offspring had improved memory even without an enriched environment."

"We were able to demonstrate that environmental enrichment during youth has dramatic additional powers," said Hartley. "It can enhance the memory in future offspring of enriched juvenile mice."

To prove that that improved memory of the offspring was not the result of better nurturing by mothers who were enriched when they were young, a number of offspring were raised by non-enriched foster mothers. Even in the offspring raised by non-enriched mothers, they still maintained an improved memory.

"This example of 'inheritance of acquired characters' was first proposed by Jean- Baptiste Lamarck in the early 1800s. However, it is incompatible with classical Mendelian genetics, which states that we inherit qualities from our parents through specific DNA sequences they inherited from their parents. We now refer to this type of inheritance as epigenetics, which involves environmentally-induced changes in the structure of DNA and the chromosomes in which DNA resides that are passed on to offspring," said Larry Feig, PhD, professor of biochemistry at Tufts University School of Medicine.

Previous research has shown that a relatively brief exposure to an enriched environment in both normal and memory-deficient mice unlocks an otherwise latent biochemical control mechanism that enhances a cellular process in nerve cells called long-term potentiation (LTP). LTP is thought to be involved in learning and memory. This enhancement was detected in pre-adolescent mice but not in adult mice, reflecting the brain's higher plasticity in the young.

"This is the first study to demonstrate an inheritance of a change in a signaling pathway that promotes LTP and enhancement of memory formation, and that defects caused by a genetic mutation can be reversed by what the mother is exposed to during her youth," said Hartley.

The phenomenon described in this study indicates that juvenile enrichment affects LTP in the next generation. However, the study found that it does not in subsequent generations because the effect of the enriched environment wears off faster in the offspring.

How brain pacemakers erase diseased messages

Fri, 01 Jun 2007 15:59:37 PST

( from http://www.rxpgnews.com ) Brain pacemakers that have helped ease symptoms in people with Parkinson's disease and other movement disorders seem to work by drowning out the electrical signals of their diseased brains.

Despite the clinical success of the devices, which have been approved by the Food and Drug Administration and can be found in the heads of about 30,000 Americans, the mechanisms by which deep brain stimulation alleviates disease symptoms aren't well understood.

Biomedical engineers at Duke University's Pratt School of Engineering have found that stimulation administered by rapid-fire electrical pulses deep in the brain produces what they call an informational lesion. By relaying a repetitious and therefore meaningless message, constant pulses overwhelm the erratic bursts of brain activity characteristic of disease.

Periodic bursts in the brains of people with tremor -- which might follow a pattern such as 'pop-pop-pop, silence, pop-pop-pop, silence' -- propagate pathological information within brain circuits, said Warren Grill, the study's lead investigator and an associate professor of biomedical engineering. If you replace that instead with a constant 'pop-pop-pop-pop-pop-pop,' you've erased that pathological information.

Grill said the high-frequency deep brain stimulation acts like a surgical lesion, another acceptable treatment for severe tremor disorders and epilepsies. But the electronic device has the advantage of being adjustable or reversible.

The researchers' report appears in a special June 2007 issue of the journal IEEE Transactions on Neural Systems and Rehabilitation Engineering, edited in part by Grill. The study was conducted by a team that included Alexis Kuncel, a doctoral student in biomedical engineering at Duke, and Scott Cooper, a neurologist at the Cleveland Clinic, with support from the National Institutes of Health.

The FDA approved the use of deep brain stimulation for Parkinson's disease in 1997. The electrical implants are also an approved therapy for other movement disorders and are at various stages of testing for the treatment of epilepsy, depression, obsessive-compulsive disorder and pain, according to Grill.

The complexity of the brain -- in which nerves project in all directions and connect with one another to form multiple, looping networks -- makes studying how deep brain stimulation works a challenge, Grill said.

Grill's team created a mathematical model of a normally functioning brain cell. The researchers then gave the model neuron the pathological pattern of activity seen in people with tremors, assembled a group of these model cells and watched what would happen when the cells were electrically stimulated at various rates and intensities.

In addition to showing how the therapy works, their model of neurons in action also revealed that stimulation delivered at too slow a pace fails to keep bad information at bay. Indeed, slower pulses can actually add to problematic bursts, they showed.

The model's findings closely parallel the clinical responses of patients, who typically experience the greatest relief from symptoms when their devices are tuned by physicians to deliver rapid pulses, Grill said. Patients' symptoms can actually worsen when the devices are dialed to a slower setting.

The intensity of stimulation also plays an important role, the study suggests, by determining the number of brain cells affected by a particular series of pulses.

A better understanding of the processes underlying deep brain stimulation could enable physicians to better fine-tune electrical implants, Grill said. That could be particularly useful for zeroing in on effective settings for implants used to treat diseases, such as epilepsy, in which seizures occur only sporadically, as well as conditions, such as depression, in which symptoms can vary widely from day to day.

In the case of tremor, physicians can alter the setting until they see the symptoms stop, Grill said. You don't have to know how it's really working.

In a condition like epilepsy, however, it's extremely unlikely that a person would have a seizure in the doctor's office, he said. Therefore, it might take months of trial and error to find the optimal setting. Grill's new model promises to streamline the process.

Relational memory requires time and sleep

Sat, 21 Apr 2007 07:19:04 PST

( from http://www.rxpgnews.com ) Memorizing a series of facts is one thing, understanding the big picture is quite another. Now a new study demonstrates that relational memory -- the ability to make logical "big picture" inferences from disparate pieces of information â is dependent on taking a break from studies and learning, and even more important, getting a good night's sleep.

Led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH), the findings appear on-line in today's Early Edition of the Proceedings of the National Academy of Sciences (PNAS).

"Relational memory is a bit like solving a jigsaw puzzle," explains senior author Matthew Walker, PhD, Director of the Sleep and Neuroimaging Laboratory at BIDMC and Assistant Professor of Psychology at Harvard Medical School (HMS). "It's not enough to have all the puzzle pieces â you also have to understand how they fit together."

Adds lead author Jeffrey Ellenbogen, MD, a postdoctoral fellow at HMS and sleep neurologist at BWH, "People often assume that we know all of what we know because we learned it directly. In fact, that's only partly true. We actually learn individual bits of information and then apply them in novel, flexible ways."

For instance, if a person learns that A is greater than B and B is greater than C, then he or she knows those two facts. But embedded within those is a third fact â A is greater than C â which can be deduced by a process called transitive inference, the type of relational memory that the researchers examined in this study.

Earlier research by Walker and colleagues had shown that sleep actively improves task-oriented "procedural memory" â for example, learning to talk, to coordinate limbs, musicianship, or to play sports. Because relational memory is fundamental to knowledge and learning, Walker and Ellenbogen decided to explore how and when this "inferential" knowledge emerges, hypothesizing that it develops during "off-line" periods and that, like procedural memory, would be enhanced following a period of sleep.

So, the researchers tested 56 healthy college students, each of whom was shown five pairs of unfamiliar abstract patterns â colorful oval shapes resembling Faberge' eggs. The students were then told that some of the patterns were "correct" while others were "incorrect," for example, Shape A wins over Shape B, Shape B wins over Shape C, and so on. All of the students learned the individual pairs but were not told that there was a hidden "hierarchy" linking all five of the pairs together.

After a 30-minute study period, the students were separated into three groups to test their understanding of the larger "big picture" relationship between the individual patterns: Group One was tested after a period of 20 minutes; Group Two was tested after a 12-hour period; and Group Three was tested after a 24-hour time span. In addition, approximately half of the students in Group Two slept during the 12-hour period, while the other half remained awake. All of the students in Group Three had a full night's sleep.

The test results showed striking differences among the three groups, especially between the students who had a period of sleep and those who remained awake.

"Group One, the students who were tested soon after their initial learning period, performed the worst," says Walker. "While they were able to learn and recall the component pieces [for example, Shape A is greater than Shape B, Shape B is greater than Shape C] they could not discern the hierarchical relationships between the pieces [Shape A is greater than Shape C] â they couldn't yet see 'the big picture.'"

Groups Two and Three, on the other hand, demonstrated a clear understanding of the interrelationship between the pairs of shapes.

"These individuals were able to make leaps of inferential judgment just by letting the brain have time to unconsciously mull things over," he says. But, perhaps most notable, he adds, when the inferences were particularly difficult, the students who had had periods of sleep in between learning and testing significantly outperformed the other groups.

"This strongly implies that sleep is actively engaged in the cognitive processing of our memories," notes Ellenbogen. "Knowledge appears to expand both over time and with sleep."

Concludes Walker, "These findings point to an important benefit [of sleep] that we had not previously considered. Sleep not only strengthens a person's individual memories, it appears to actually knit them together and help realize how they are associated with one another. And this may, in fact, turn out to be the primary goal of sleep: You go to bed with pieces of the memory puzzle, and awaken with the jigsaw completed."

Phase locking of hippocampal interneuron membrane potential

Tue, 05 Dec 2006 08:15:57 PST

( from http://www.rxpgnews.com ) If I can't remember this morning where I put my car keys last night, it's due to my memory failing me again. Scientists at the Max Planck Institute for Medical Research in Heidelberg have been investigating how memories might be consolidated. Their new study offers the hitherto strongest proof that new information is transferred between the hippocampus, the short term memory area, and the cerebral cortex during sleep. According to their findings and contrary to previous assumptions, the cerebral cortex actively controls this transfer. The researchers developed a new technique for their investigations which promises previously impossible insight into the largely under-researched field of information processing in the brain (Nature Neuroscience, November 2006).

The question of how the brain stores or discards memories still remains largely unexplained. Many brain researchers regard the consolidation theory as the best approach so far. This states that fresh impressions are first stored as short-term memories in the hippocampus. They are then said to move within hours or a few days - usually during deep sleep - into the cerebral cortex where they enter long-term memory. Investigations by Thomas Hahn, Mayank Mehta and the Nobel Prize winner Bert Sakmann from the Max Planck Institute for Medical Research in Heidelberg have now shed new light on the mechanisms that create memory. According to their findings, the areas of the brain work together, but possibly in a different way from that previously assumed. "This is a technically sophisticated study which could have considerable influence on our understanding of how nerve cells interact during sleep consolidation," confirmed Edvard Moser, Director of the Centre for the Biology of Memory in Trondheim, Norway.

It has been difficult up to now to use experiments to examine the brain processes that create memory. The scientists in Heidelberg developed an innovative experimental approach especially for this purpose. They succeeded in measuring the membrane potential of individual interneurones (neurones that suppress the activity of the hippocampus) in anaethetised mice. At the same time, they recorded the field potential of thousands of nerve cells in the cerebral cortex. This allowed them to link the behaviour of the individual nerve cells with that of the cerebral cortex. The researchers discovered that the interneurones they examined are active at almost the same time as the field potential of the cerebral cortex. There was just a slight delay, like an echo.

This was a surprising finding, because the interneurones suppress those neurones in the hippocampus which are supposed to write information to the cerebral cortex precisely during phases of high activity. According to Mayank Mehta the result can be interpreted in very different ways. "Either the mechanism contributes to memory consolidation, or the information transfer from one part of the brain to another during sleep does not proceed as we have previously assumed." The brain researchers now want to find out which of the possible explanations applies.

In any case, the scientists can use their new experimental method to investigate many other open questions in brain research. Thomas Hahn emphasised: "Putting the behaviour of a single neuron in the context of wider-scale patterns of activity promises to yield completely new insights into the principles according to which our brain is organised."

Poor memory could signal heart disease

Sun, 26 Nov 2006 14:10:34 PST

( from http://www.rxpgnews.com ) London, Nov 26 - People who have poor memory and react slowly may face a higher risk of cardiovascular or respiratory disease, says a new study.

Beverly Shipley and researchers of Edinburgh University surveyed the mental agility of over 6,400 people aged between 18 and 99 from across Britain over the past two decades.

They found that differences in mental ability were a risk factor for certain vascular health conditions, reported the online edition of BBC news.

More than 1,500 members of the group had died by 2005, when the 21-year research ended, the report said.

It was found that longer reaction time was associated with higher death rates even after taking into account other factors linked with heart disease like physical activity, blood pressure, body mass index and smoking.

Shipley added that lower than average mental agility led to at least a 10 percent greater chance of developing heart disease.

One of the surprising outcomes of the research was that both younger and older adults exhibited the same link between cognition and heart disease mortality.

A possible explanation was that human reaction time was an indicator of a body with better 'system integrity', meaning how well it is wired together.

But Shipley still was not sure why cognition and reaction time were related to mortality.

Memories: It's all in the packaging

Fri, 10 Nov 2006 17:07:37 PST

( from http://www.rxpgnews.com ) Researchers at UC Irvine have found that how much detail one remembers of an event depends on whether a certain portion of the brain is activated to package the memory.

The research may help to explain why sometimes people only recall parts of an experience such as a car accident, and yet vividly recall all of the details of a similar experience.

In experiments using functional magnetic resonance imaging (fMRI), the scientists were able to view what happened in the brains of subjects when they experienced an event made up of multiple contextual details. They found that participants who later remembered all aspects of the experience, including the details, used a particular part of the brain that bound the different details together as a package at the time the event occurred. When this brain region wasnt activated to bind together the details, only some aspects of an event were recalled. The findings appear in the current issue of Neuron.

This study provides a neurological basis for what psychologists have been telling us for years, said Michael Rugg, director of UCIs Center for the Neurobiology of Learning and Memory and senior author of the paper. You cant get out of memory what you didnt put into it. It is not possible to remember things later if you didnt pay attention to them in the first place.

The scientists presented 23 research subjects with a list of words while they underwent an fMRI scan. The words were in different colors and would appear in one of four quadrants on a screen. The subjects had to decide whether the words represented an animate or inanimate object. Later, the participants were presented the words again, interspersed with words they had not seen before, and asked if they remembered seeing those words before. They were also asked if they remembered in what color the word had originally been and in which of the four quadrants it had originally appeared.

If the participant could later remember the color of the word, a particular area of the brain associated with color processing was especially active during learning. If the subject later remembered the location of the word, activity was seen in an area associated with spatial processing. But if the subject remembered the word, the color and the location, then another critical brain region became involved. The researchers observed enhanced activity in the intra-parietal sulcus, a part of the parietal cortex. It appears that this region is responsible for binding together all the features of a particular memory so that contextual details, as well as more central aspects of the event such as the identity of the word, can later be recalled.

We know that if the intra-parietal sulcus is damaged, then someone cannot attend to multiple aspects of the same object, such as its size and color, said Melina Uncapher, a graduate student researcher and lead author of the study. This study provides empirical evidence for how critical this region is for bringing the constituents of a memory together in the brain.

Memory is more than a sum of its parts. A complete memory of an event requires that the features of the event be brought together and processed by the brain as a common perceptual representation, before being stored.

Atrial Fibrillation linked to Reduced Cognitive Performance

Tue, 24 Oct 2006 18:09:37 PST

( from http://www.rxpgnews.com ) (Boston) Researchers from Boston University have found a link between atrial fibrillation and low cognitive performance in men. Using a subset of participants from the Framingham Offspring Study, part of the long-running Framingham Heart Study, the team found an association between atrial fibrillation and poor mental functioning. The results appear in the current issue of the Journal of Stroke and Cerebrovascular Disease.

The research team, led by Merrill Elias, a research professor of epidemiology in BUs Mathematics and Statistics Department, found a link between atrial fibrillation and reduced cognitive function in areas such as visual organization, memory, attention, and concentration. Atrial fibrillation, the most common cardiac arrhythmia, is a major risk factor for stroke and has been associated with reduced cardiac output, decreased blood flow to the brain, blood vessel blockages, and brain lesions.

The results of the new study showed that men with the abnormal heart rhythm, but free from senile dementia or stroke, had significantly lower scores on multiple tests of mental ability compared to men with no presence of atrial fibrillation.

Elias and his team related the presence of atrial fibrillation in participants to cognitive performance using the Framingham Offspring cognitive test battery. Relations between atrial fibrillation and test performance were statistically adjusted for relations between multiple cardiovascular disease risk factors, stroke, cardiovascular events, and treatment with drugs, coronary artery bypass graft surgery, age, and education. With these adjustments, atrial fibrillation was correlated to lower performance for the following abilities: abstract reasoning, visual memory, visual organization, verbal memory, scanning and tracking, and executive functioning.

The study included 1,011 Framingham Offspring Study males 59 with atrial fibrillation and 952 without. Women were excluded from the study due to the low incidence of atrial fibrillation.

A variety of factors linking atrial fibrillation to decreased cognitive performance have been suggested, including undiagnosed stroke, lesions on the brain, and reduced cardiac output, said Elias. What we need now are additional studies that will hopefully lead to a better understanding of the underlying mechanisms that cause men with atrial fibrillation to have poorer cognition.

The Framingham Heart Study began in 1955 and has followed three generations of participants, measuring the incidence of cardiovascular disease and stroke and determining the risk of various associated factors. The study, based in Framingham, MA., started before cardiovascular risk factors for heart disease and stroke were well understood and before patients were routinely treated for atrial fibrillation.

Human Memory Gene Identified

Fri, 20 Oct 2006 23:36:37 PST

( from http://www.rxpgnews.com ) Researchers at the Translational Genomics Research Institute (TGen) today announced the discovery of a gene that plays a significant role in memory performance in humans. The findings, reported by TGen and research colleagues at the University of Zurich in Switzerland, Banner Alzheimer's Institute, and Mayo Clinic Scottsdale, appear in the October 20 issue of Science. The study details how researchers associated memory performance with a gene called Kibra in over 1,000 individuals --both young and old-- from Switzerland and Arizona. This study is the first to describe scanning the human genetic blueprint at over 500,000 positions to identify cognitive differences between humans.

Image Courtesy: NHGRI

"Using the latest whole-genome association technologies, we have shed light on the fundamental biological process of human memory performance," said Dr. Dietrich Stephan, Director of TGen's Neurogenomics Division and a senior author of the paper. "The capacity to remember is a defining feature of humans and we can now use this new understanding to develop drugs that will improve memory function."

Researchers at the University of Zurich, collaborating with colleagues at Arizona's Banner Alzheimer's Institute, Mayo Clinic Scottsdale, and the Arizona Alzheimer's Consortium, collected DNA samples from cognitively healthy people and measured memory performance. TGen researchers screened the collected DNA samples using the whole-genome microarray technology. Researchers then combined the scan data with the memory performance test results and found a connection between Kibra and memory.

According to the study's lead author, Dr. Andreas Papassotiropoulos, professor at the University of Zurich, "The link between Kibra and memory could lead to new treatments for memory loss and possibly help improve memory in patients with memory disorders such as Alzheimer's disease."

Not only did the research team identify that the Kibra gene was associated with memory performance, but they also showed that the gene is turned on in the hippocampus, a brain region known to be critical to memory function.

"Using sophisticated functional brain imaging techniques, we showed that individuals who had a version of the gene that is related to poorer memory potential had to tax their brains harder to remember the same amount of information," said Dr. Dominique de Quervain, professor at the University of Zurich.

"Researchers now have enough of the 'letters' to read the 'genetic book of life' with unprecedented power," said Dr. Eric Reiman, executive director of the Banner Alzheimer's Institute and one of the study investigators. "We're excited about the chance to identify a gene that accounts for some of variation in normal human memory and to use this information in the discovery of promising new memory-enhancing treatments."

Until now, researchers did not have access to the high-density technology to examine the genetic components associated with memory performance. The team at TGen used Affymetrix Human Mapping 500K Arrays to simultaneously analyze 500,000 genetic markers from the people who were tested. They made the memory discovery by comparing the genetic blueprint of people with good memory to people with poor memory; memory performance was based on a series of gold-standard tests for all individuals. The researchers then validated their discovery by replicating the Kibra gene finding in two separate and distinct groups of subjects.

"This memory study is a perfect example of how the use of advanced technologies in human genetics yields fundamental discoveries," said Dr. Stephen P.A. Fodor, Chairman and CEO at Affymetrix, the Santa Clara, Calif.-based manufacturer of the technology.

The impact of the study is that it gives the research community a new and important handhold into truly understanding the process of memory. The ramifications of this report are ultimately developing new and effective medicines that can combat memory loss, and that might also help improve memory in people with memory disorders like Alzheimer's disease.

The team has already begun working on new drugs to restore memory function in age-related memory loss and diseases that have a memory loss component.

Researchers at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona have used the Affymetrix 500K Array to discover a gene--called Kibra--associated with memory performance in humans. The team's findings may be used to develop new medicines for memory-based diseases such as Alzheimer's and Parkinson's by providing scientists with a better understanding of how memory works at the molecular level.

"Using the latest Affymetrix 500K Array, we have shed light on the fundamental biological process of human memory performance," said Dr. Stephan. "We can use this new understanding to develop drugs that will improve memory function."

Until now, researchers did not have access to the high-density technology needed to examine the genetic components associated with memory performance. The team at TGen used Affymetrix Human Mapping 500K Arrays to analyze 500,000 DNA markers simultaneously, providing a genetic blueprint for the memory-study participants. The researchers discovered the Kibra gene by comparing the genetic blueprints of people with good memory vs. poor memory and looking for the genetic variations consistently present in one group, but not the other. They then validated their discovery by replicating the Kibra gene finding in two separate and distinct groups of subjects.

"This memory study is a perfect example of how the use of advanced technologies in human genetics yields fundamental discoveries," said Stephen P.A. Fodor, Ph.D., chairman and CEO at Affymetrix.

How the Brain Loses Plasticity of Youth

Fri, 18 Aug 2006 18:50:37 PST

( from http://www.rxpgnews.com ) A protein once thought to play a role only in the immune system could hold a clue to one of the great puzzles of neuroscience: how do the highly malleable and plastic brains of youth settle down into a relatively stable adult set of neuronal connections? Harvard Medical School researchers report in the August 17 Science Express that adult mice lacking the immune system protein paired-immunoglobulin like receptor-B (PirB) had brains that retained the plasticity of much younger brains, suggesting that PirB inhibits such plasticity.

Intriguingly, brains of immature PirB-deprived mice also exhibited greater plasticity than brains endowed with the protein. Taken together, the results have important implications for the future study and repair of the brain. "Our study of mutant mice lacking PirB function reveals that at all ages, even during critical periods when circuits are prone to change, there are active molecular mechanisms that function to limit synaptic plasticity," said Josh Syken, HMS instructor in neurobiology and lead author of the study.

One way to promote new connections in brains damaged by disease or injury might be to target PirB. "The implications here should attract broad interest outside the field of developmental neuroscience because molecules and mechanisms that oppose neuronal plasticity represent new targets for therapy to re-establish damaged connections following spinal cord injury, head injury or stroke," said Syken, who carried out the study with Carla Shatz, Nathan Marsh Pusey professor of neurobiology at HMS, and colleagues.

Plasticity, the ability of functional brain circuits to change in response to experience-dependent neuronal activity, is largely restricted to critical periods of development. In their classic Nobel-prize winning experiments, David Hubel and Torsten Weisel showed that visual areas of the brain are responsive to environmental cues during a discrete period early in life, after which they do not change. Researchers have successfully identified proteins that promote such critical periods of plasticity but less is known about the proteins that stabilize neuronal connections.

Several years ago, Shatz and colleagues made the surprising discovery that MHC Class I genes are turned on in neurons by neuronal activity and in fact are required for normal synaptic plasticity. In the immune system, MHC Class I proteins teach immune cells which cells to attack. They do this by interacting with a large number of receptors found on the surface of immune cells. Syken, Shatz and colleagues wondered whether such receptors might also be expressed in neurons and involved in MHC Class I-mediated synaptic plasticity.

Using a method called in situ hybridization, they found that the MHC Class I receptor PirB is expressed widely throughout the brain and at all ages. To see how PirB was functioning, they generated a mouse deficient in PirB. At first sight, the mutant's brain appeared normal. To get a better sense of how PirB might be affecting plasticity, they decided to focus on the visual cortex.

In their earlier work, Hubel and Weisel showed that suturing or removing one eye causes projections from the remaining eye to invade the area that normally represents the blocked eye. This shift is strictly limited to a critical period of development early in life. Syken and his colleagues sutured one eye in their adult mutant mice, and also in controls, for several days. They exposed the open eye to light and, using the activity-sensitive gene Arc as their guide, looked to see which neurons in the cortex were activated. The PirB mutant adults exhibited a robust expansion of the area in visual cortex that responds to the open eye, suggesting that new connections representing the open eye had formed. They repeated the experiment with younger mice and found, somewhat unexpectedly, that plasticity was enhanced even during the immature period.

"Other factors have been shown to restrict plasticity after the critical period, but we believe that this is one of the first proteins shown to act in this way throughout life," Syken said. "Our discovery implies that there are mechanisms that enable, and also those that oppose synaptic plasticity in a push-pull fashion."

"Our discovery underscores further the fascinating and common molecular parallels between the nervous system and the immune system, where PirB was first studied. The discovery of a neuronal receptor for MHC Class I opens up a completely new avenue for thinking about broader roles for this family of molecules beyond the immune system," he said.

Apple Juice Inproves Memory By Boosting Acetylcholine Production

Wed, 02 Aug 2006 12:00:37 PST

( from http://www.rxpgnews.com ) For those who think that apple juice is a kid's drink, think again. Apples and apple juice may be among the best foods that baby boomers and senior citizens could add to their diet, according to new research that demonstrates how apple products can help boost brain function similar to medication.

Animal research from the University of Massachusetts Lowell (UML) indicates that apple juice consumption may actually increase the production in the brain of the essential neurotransmitter acetylcholine, resulting in improved memory. Neurotransmitters such as acetylcholine are chemicals released from nerve cells that transmit messages to other nerve cells. Such communication between nerve cells is vital for good health, not just in the brain, but throughout the body.

"We anticipate that the day may come when foods like apples, apple juice and other apple products are recommended along with the most popular Alzheimer's medications," says Thomas Shea, Ph.D., director of the UML Center for Cellular Neurobiology and Neurodegeneration Research.

The role of acetylcholine in the brain is not a new area of research. Alzheimer's medication studies start with the premise that increasing the amount of acetylcholine in the brain can help to slow mental decline in people with Alzheimer's disease. Testing a similar hypothesis, the UML research team found that having animals consume antioxidant-rich apple juice had a comparable and beneficial effect.

In this novel animal study at UML, adult (9-12 months) and old (2-2.5 years) mice, some specially bred to develop Alzheimer's-like symptoms, were fed three different diets (a standard diet, a nutrient-deficient diet, and a nutrient-deficient diet supplemented with apple components (in this case, apple juice concentrate was added to their drinking water).

Among those fed the apple juice-supplemented diet, the mice showed an increased production of acetylcholine in their brains. Also, after multiple assessments of memory and learning using traditional Y maze tests, researchers found that the mice who consumed the apple juice-supplemented diets performed significantly better on the maze tests.

"It was surprising how the animals on the apple-enhanced diets actually did a superior job on the maze tests than those not on the supplemented diet," remarks Dr. Shea.

Earlier studies by Shea's research team had strongly suggested apples must possess a unique mix of antioxidants that improve cognition and memory via inhibition of oxidation in the brain. Those results encouraged Shea to evaluate the neurotransmitter effect, as is done in the current study. Medications given to humans with Alzheimer's disease have been shown to inhibit the production of specific enyzmes (cholinesterase inhibitors) that break down acetylcholine in the brain. The end result in the animal study is similar there are more of these critical messengers remaining in the brain to enhance memory.

The results obtained were from the animals consuming moderate amounts of apple juice --comparable to drinking approximately two 8 oz. glasses of apple juice or eating 2-3 apples a day. The findings also suggest that the apple-supplemented diet was most helpful in the framework of an overall healthy diet.

Shea concludes, "The findings of the present study show that consumption of antioxidant-rich foods such as apples and apple juice can help reduce problems associated with memory loss."

Shea also notes that a human clinical study evaluating consumption of apple products will begin in the near future.

Fresh Light on How we form New Memories

Mon, 31 Jul 2006 11:53:37 PST

( from http://www.rxpgnews.com ) A study conducted by researchers at Carnegie Mellon University and the University of Pittsburgh involving an amnesia-inducing drug has shed light on how we form new memories.

For a paper to be published in the July edition of the journal Psychological Science, researchers gave participants material to remember in two experimental sessions -- once after being injected with a saline placebo and once after an injection of midazolam, a drug used to relieve anxiety during surgical procedures that also causes short-term anterograde amnesia, the most common form of amnesia. Anterograde amnesia, which was portrayed in the film "Memento," impairs a person's ability to form new memories while leaving old ones unharmed.

The study revealed that the drug prevented people from linking a studied item to the experimental context. That linkage is necessary for a process known as recollection, in which people retrieve contextual details involved in the experience of studying the information. People sometimes recognize something as having been studied without using recollection (in this case, without remembering details of the study event) if the item seems sufficiently familiar -- a process called familiarity. Although the recollection process was affected by the drug, the familiarity process was not. This is the same pattern that is found with patients suffering from anterograde amnesia. They are unable to form new associations, severely limiting the accuracy of their recognition judgments.

"This helps us understand the general functions of memory. It helps us to relate, for example, the memory declines seen in old age to those seen in patients with hippocampal damage," said Lynne Reder, a professor of psychology at Carnegie Mellon and the study's lead author.

Using a double-blind, within-subject protocol, the scientists compared the participants' performance on the test after studying the material either under the influence of midazolam or after receiving an injection of a saline placebo. In both sessions, participants viewed words, photographs of faces and landscapes, and abstract pictures one at a time on a computer screen. Twenty minutes later, they were shown the words and images again, one at a time. Half of the images they had seen earlier, and half were new. They were then asked whether they recognized each one.

The researchers predicted that the more participants relied on recollection with saline, the more they would be hurt under the influence of midazolam. Their findings matched those predictions. Researchers found that the participants' memory while in the placebo condition was best for words, but the worst for abstract images. Midazolam impaired the recognition of words the most and did not affect recognition of abstract pictures.

The experiment further reinforced the thought that the ability to recollect depends on the ability to link the stimulus to a context. While the words were very concrete and therefore easy to link to the experimental context, the photographs were of unknown people and unknown places (not, for example, of Marilyn Monroe or the Eiffel Tower) and thus hard to distinctively label. The abstract images were also unfamiliar and not unitized into something that could be described with a single word (such as Picasso's "Guernica"). This meant that a person could not easily link the image with a context, regardless of drug condition.

Multi-tasking affects the brain's learning systems

Thu, 27 Jul 2006 08:55:37 PST

( from http://www.rxpgnews.com ) Multi-tasking affects the brain's learning systems, and as a result, we do not learn as well when we are distracted, UCLA psychologists report this week in the online edition of Proceedings of the National Academy of Sciences.

"Multi-tasking adversely affects how you learn," said Russell Poldrack, UCLA associate professor of psychology and co-author of the study. "Even if you learn while multi-tasking, that learning is less flexible and more specialized, so you cannot retrieve the information as easily. Our study shows that to the degree you can learn while multi-tasking, you will use different brain systems.

"The best thing you can do to improve your memory is to pay attention to the things you want to remember," Poldrack added. "Our data support that. When distractions force you to pay less attention to what you are doing, you don't learn as well as if you had paid full attention."

Tasks that require more attention, such as learning calculus or reading Shakespeare, will be particularly adversely affected by multi-tasking, Poldrack said.

The researchers used functional magnetic resonance imaging (fMRI) to examine brain activity and function, a technique that uses magnetic fields to spot active brain areas by telltale increases in blood oxygen.

Participants in the study, who were in their 20s, learned a simple classification task by trial-and-error. They were asked to make predictions after receiving a set of cues concerning cards that displayed various shapes, and divided the cards into two categories. With one set of cards, they learned without any distractions. With a second set of cards, they performed a simultaneous task: listening to high and low beeps through headphones and keeping a mental count of the high-pitch beeps. While the distraction of the beeps did not reduce the accuracy of the predictions -- people could learn the task either way -- it did reduce the participants' subsequent knowledge about the task during a follow-up session.

When the subjects were asked questions about the cards afterward, they did much better on the task they learned without the distraction. On the task they learned with the distraction, they could not extrapolate; in scientific terms, their knowledge was much less "flexible."

This result demonstrates a reduced capacity to recall memories when placed in a different context, Poldrack said.

"Our results suggest that learning facts and concepts will be worse if you learn them while you're distracted," Poldrack said.

Different forms of memory are processed by separate systems in the brain, he noted. When you recall what you did last weekend or try to remember someone's name or your driver's license number, you are using a type of memory retrieval called declarative memory. (Patients with Alzheimer disease have damage in these brain areas.) When you remember how to ride a bicycle or how to play tennis, you are using what is called procedural memory; this requires a different set of brain areas than those used for learning facts and concepts, which rely on the declarative memory system. The beeps in the study disrupted declarative memory, said Poldrack, who also studies how the types of memory are related.

The brain's hippocampus -- a sea-horse-shaped structure that plays critical roles in processing, storing and recalling information -- is necessary for declarative memory, Poldrack said. For the task learned without distraction, the hippocampus was involved. However, for the task learned with the distraction of the beeps, the hippocampus was not involved; but the striatum was, which is the brain system that underlies our ability to learn new skills.

The striatum is the brain system damaged in patients with Parkinson disease, Poldrack noted. Patients with Parkinson's have trouble learning new motor skills but do not have trouble remembering the past.

"We have shown that multi-tasking makes it more likely you will rely on the striatum to learn," Poldrack said. "Our study indicates that multi-tasking changes the way people learn."

The researchers noted that they are not saying never to multi-task, just don't multi-task while you are trying to learn something new that you hope to remember. Listening to music can energize people and increase alertness. Listening to music while performing certain tasks, such as exercising, can be helpful. But tasks that distract you while you try to learn something new are likely to adversely affect your learning, Poldrack said.

"Concentrate while you're studying," he said.

Music thought to enhance intelligence

Sat, 24 Jun 2006 16:05:37 PST

( from http://www.rxpgnews.com ) A recent volume of the Annals of the New York Academy of Sciences takes a closer look at how music evolved and how we respond to it. Contributors to the volume believe that animals such as birds, dolphins and whales make sounds analogous to music out of a desire to imitate each other. This ability to learn and imitate sounds is a trait necessary to acquire language and scientists feel that many of the sounds animals make may be precursors to human music.

Another study in the volume looks at whether music training can make individuals smarter. Scientists found more grey matter in the auditory cortex of the right hemisphere in musicians compared to nonmusicians. They feel these differences are probably not genetic, but instead due to use and practice.

Listening to classical music, particularly Mozart, has recently been thought to enhance performance on cognitive tests. Contributors to this volume take a closer look at this assertion and their findings indicate that listening to any music that is personally enjoyable has positive effects on cognition. In addition, the use of music to enhance memory is explored and research suggests that musical recitation enhances the coding of information by activating neural networks in a more united and thus more optimal fashion.

Other studies in this volume look at music's positive effects on health and immunity, how music is processed in the brain, the interplay between language and music, and the relationship between our emotions and music.

Our grip on reality is slim

Sat, 24 Jun 2006 03:09:37 PST

( from http://www.rxpgnews.com ) The neurological basis for poor witness statements and hallucinations has been found by scientists at UCL (University College London). In over a fifth of cases, people wrongly remembered whether they actually witnessed an event or just imagined it, according to a paper published in NeuroImage this week.

Dr Jon Simons and Dr Paul Burgess led the study at the UCL Institute of Cognitive Neuroscience. Dr Burgess said: "In our tests volunteers either thought they had imagined words which they had actually been shown or said they had seen words which in fact they had just imagined - in over 20 per cent of cases. That is quite a lot of mistakes to be making, and shows how fallible our memory is - or perhaps, how slim our grip on reality is!

"Our work has implications for the validity of witness statements and agrees with other studies that show that our mind sometimes fills in memory gaps for us, and we confuse what we imagined occurred in a situation - which is related to what we expect to happen or what usually happens - with what actually happened.

"Most of us, though, have a critical reality monitoring function so that we are able to distinguish well enough between what is real and what is imagined and our imagination does not have too great an impact on our lives - unless the reality check system breaks down such as after stroke or in cases of schizophrenia."

The study found that the areas that were activated while remembering whether an event really happened or was imagined in healthy subjects are the very same areas that are dysfunctional in people who experience hallucinations.

Dr Burgess said: "We believe that hallucinations are caused by a difficulty in discriminating information present in the outside world from information that is imagined. In schizophrenia the difficulty you have in separating reality from imagined events becomes exaggerated so some people have hallucinations and hear voices that simply aren't there." These results indicate a link between the brain areas implicated in schizophrenia and the regions that support the ability to discriminate between perceived and imagined information.

In the tests, healthy subjects were shown 96 well-known word pairs from pop culture such as 'Laurel and Hardy', 'bacon and eggs', and 'rock and roll'. The participants were asked to count the number of letters in the second word of the pair. Often the second word wasn't actually shown and the subject had to imagine the word such as 'Laurel and ?'.

Participants were then asked which of the second words they had actually seen on screen and which ones they had only imagined. The subjects' brain activity was observed using fMRI scans while they remembered whether words had been imagined or seen on screen.

When people accurately remembered whether they had actually seen a word or just imagined it brain activity in the key areas increased many of which are found in brain area 10, which is involved in imagination and reality checking, develops last in the brain and is twice as big in humans as in other animals. In the people who did not remember correctly, activation in brain area 10 was reduced.

Short term synaptic plasticity play a widespread role in information processing

Fri, 23 Jun 2006 00:32:37 PST

( from http://www.rxpgnews.com ) Animals' neurons, and the synapses that connect them, are constantly changing. This plasticity is thought to underlie learning and memory. Take the rat in the maze. As he learns to navigate a new environment, familiarity with the space is reflected in the neuronal activity of a small almond-shaped brain structure called the hippocampus. Neurons in the hippocampus are generally quiescent. But when the rat meanders into a spot that a specific neuron prefers, called its place field, the neuron responds with high-frequency bursts of spikes. As the rat's familiarity with the maze increases over only a few minutes, so does the reliability by which hippocampal neurons respond to their preferred place. This short-term experience modifies the neurons' responses, and very likely the synapses, although the synaptic mechanisms of short-term plasticity in this context have not been fully described.

A new study takes a step forward in understanding the most basic level of this process: the short-term plasticity at hippocampal synapses that result from processing incoming signals resembling place-field responses. The researchers, Vitaly Klyachko and Charles Stevens, discovered a novel short-term plasticity mechanism by which excitatory and inhibitory synapses can selectively amplify high-frequency bursts.

For the study, the researchers used slices of the rat's hippocampus, focusing on cells from two particular regions, called CA1 and CA3, known for their role in encoding information about the animal's position. The researchers recorded long series of this firing activity, which they then used to stimulate two classes of hippocampal neurons: excitatory neurons, whose function is to spur neurons downstream to fire; and inhibitory neurons, which suppress neurons downstream.

In the hippocampus, these neurons form basic circuit elements, among which a feed-forward loop is one of the most common. In its simplest form, these loops feature an excitatory neuron connected to both an inhibitory neuron and an output neuron, and the inhibitory neuron is also connected to the output neuron. In this simple triangular network, incoming signals trigger both the excitatory and inhibitory neurons at once, and then the inhibitory neuron activates its synapses with a delay of a few milliseconds. From the output neuron's point of view, the incoming excitatory signals are closely followed by the inhibitory ones.

Several previous studies that tried to sort out how these neurons function during processing of incoming signals that resemble natural activity failed to produce coherent outputs from the neurons. These incoherent outputs may have resulted from the fact that the neurons were held at room temperature; as Klyachko and Stevens had shown before, short-term plasticity works differently at room temperature than at body temperature. To avoid the temperature problem in this study, Klyachko and Stevens held the brain slices at near body temperature.

With short-term plasticity, a synapse's response to any one signal depends on the signals it received in the previous few seconds. Synapses can sense when they're receiving a high number of impulses per secondthat is, a high-frequency signal. Klyachko and Stevens found that, as long as the incoming signal was above a certain average rate, around 10 Hz, then the synapses would flip from a baseline state to an active state. The excitatory synapses became more excitatory, amplifying incoming signals. The inhibitory synapses responded oppositely, damping down their activity. Surprisingly, for any signals with higher frequency, these synapses' responses stayed constant even when the incoming signal rose to much higher frequencies, such as 100 Hz. The researchers also found that the excitatory and inhibitory synapses had mirror-image responses: when the excitatory synapses amplified a specific portion of a signal, the inhibitory synapses damped down their response at the same time.

When these two types of cells are wired together in a feed-forward loop, the researchers found that the excitatory and inhibitory synapses acted in concert, filtering out low-frequency signals while amplifying high-frequency signals. Thus, the study shows a function for the hippocampus's feed-forward loops not seen in earlier studies. It also shows a new role for inhibitory synapses: amplifying signals.

In this study, hippocampal neurons used short-term plasticity to filter neuronal signals for high-frequency events that encode important information for the animal. As the authors argue, this plasticity could also play a widespread role in information processing in the brain. Short-term plasticity may provide the mechanism by which animals' quickly changing brains help them navigate and comprehend the world.

Brain Rewards Curiosity with Shot of Natural Opiates

Wed, 21 Jun 2006 00:05:37 PST

( from http://www.rxpgnews.com ) Neuroscientists have proposed a simple explanation for the pleasure of grasping a new concept: The brain is getting its fix.

The "click" of comprehension triggers a biochemical cascade that rewards the brain with a shot of natural opium-like substances, said Irving Biederman of the University of Southern California. He presents his theory in an invited article in the latest issue of American Scientist.

"While you're trying to understand a difficult theorem, it's not fun," said Biederman, professor of neuroscience in the USC College of Letters, Arts and Sciences.

"But once you get it, you just feel fabulous."

The brain's craving for a fix motivates humans to maximize the rate at which they absorb knowledge, he said.

"I think we're exquisitely tuned to this as if we're junkies, second by second."

Biederman hypothesized that knowledge addiction has strong evolutionary value because mate selection correlates closely with perceived intelligence.

Only more pressing material needs, such as hunger, can suspend the quest for knowledge, he added.

The same mechanism is involved in the aesthetic experience, Biederman said, providing a neurological explanation for the pleasure we derive from art.

"This account may provide a plausible and very simple mechanism for aesthetic and perceptual and cognitive curiosity."

Biederman's theory was inspired by a widely ignored 25-year-old finding that mu-opioid receptors binding sites for natural opiates increase in density along the ventral visual pathway, a part of the brain involved in image recognition and processing.

The receptors are tightly packed in the areas of the pathway linked to comprehension and interpretation of images, but sparse in areas where visual stimuli first hit the cortex.

Biederman's theory holds that the greater the neural activity in the areas rich in opioid receptors, the greater the pleasure.

In a series of functional magnetic resonance imaging trials with human volunteers exposed to a wide variety of images, Biederman's research group found that strongly preferred images prompted the greatest fMRI activity in more complex areas of the ventral visual pathway. (The data from the studies are being submitted for publication.)

Biederman also found that repeated viewing of an attractive image lessened both the rating of pleasure and the activity in the opioid-rich areas. In his article, he explains this familiar experience with a neural-network model termed "competitive learning."

In competitive learning (also known as "Neural Darwinism"), the first presentation of an image activates many neurons, some strongly and a greater number only weakly.

With repetition of the image, the connections to the strongly activated neurons grow in strength. But the strongly activated neurons inhibit their weakly activated neighbors, causing a net reduction in activity. This reduction in activity, Biederman's research shows, parallels the decline in the pleasure felt during repeated viewing.

"One advantage of competitive learning is that the inhibited neurons are now free to code for other stimulus patterns," Biederman writes.

This preference for novel concepts also has evolutionary value, he added.

"The system is essentially designed to maximize the rate at which you acquire new but interpretable [understandable] information. Once you have acquired the information, you best spend your time learning something else.

"There's this incredible selectivity that we show in real time. Without thinking about it, we pick out experiences that are richly interpretable but novel."

The theory, while currently tested only in the visual system, likely applies to other senses, Biederman said.

Sleepy fruit flies provide clues to learning and memory

Fri, 16 Jun 2006 00:53:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of Pennsylvania School of Medicine have discovered that a brain region previously known for its role in learning and memory also serves as the location of sleep regulation in fruit flies. Through further examination of this brain structure, researchers hope to shed light on sleep regulation and its role in memory.

Despite its importance in everyday human function, very little is known about the regulation of sleep. In search of the underlying brain region responsible for sleep regulation, senior author Amita Sehgal, PhD, Professor of Neuroscience and a Howard Hughes Medical Institute (HHMI) Investigator, and colleagues turned their attention to the fruit fly.

"Fruit flies and humans share similar resting patterns," explains Sehgal. "Like humans, the sleeping states of fruit flies are characterized by periods of immobility over a twenty-four hour period, during which the fruit flies demonstrate reduced responsiveness to sensory stimuli."

By tinkering with the gene expression of multiple regions of the fruit fly brain, the research team was able to zero in on the adult mushroom body as the sleep center of the brain. They reported their findings in last week's issue of Nature.

To locate the brain region involved in sleep regulation, Sehgal manipulated the activity of an enzyme known as protein kinase A (PKA). Previous work in Sehgal's lab revealed that the higher the level of PKA activity, the lower the period of immobility, or sleep, in the fruit fly. By building upon this work, Sehgal and others set out to increase PKA activity in various regions of the brain and examine the subsequent sleeping patterns in the fruit flies. "Sleeping fruit flies" were defined as those that remained immobile for at least five minutes.

"From the beginning, we took the unbiased approach," explains Sehgal. "We targeted PKA activity to different areas of the fly brain to find out where PKA acts to regulate sleep."

Sehgal was able to selectively turn on PKA activity in a variety of brain locations, which promoted PKA expression in designated regions. Of the different regions targeted, only two regions, both present in the adult mushroom bodies, led to changes in sleeping patterns of fruit flies. The fly mushroom body has been likened to the human hippocampus. The changes in sleep caused by the increased PKA activity in the adult mushroom bodies highlighted this region as the sleep-regulating region of the fruit fly brain.

When PKA activity was expressed in one of the two distinct regions of the mushroom bodies, increased sleep occurred while expression in the other region decreased sleep in the flies. Thus, the adult mushroom bodies possess both sleep-promoting and sleep-inhibiting areas.

"Although people typically think of mushroom bodies as possessing similar functions to the human hippocampus, the site where long-term memories are made, our lab tends to think of the mushroom bodies functioning more like the thalamus, the relay station through which most sensory input to the brain is targeted," explains Sehgal. "Previous research links the thalamus to a role in human sleep." (There is no human structure that is anatomically similar to the adult mushroom bodies of fruit flies.)

Identifying the role of adult mushroom bodies in sleep may offer insight into how and why sleep is needed to assist in learning and memory consolidation. In mammals, sleep deprivation suppresses the performance of learned tasks, and sleep permits memory consolidation. Distinct anatomical regions of adult mushroom bodies have been shown to be important for at least some forms of memory in fruit flies.

In a paper also published last week in Current Biology, Sehgal and colleagues showed that serotonin affects sleep in fruit flies by acting at the site of the adult mushroom bodies.

Sehgal's lab reduced the function of three types of serotonin receptors in the brains of fruit flies (5HT1A, 5HT1B, and 5HT2). The reduced 5HT1A receptor activity in the fruit flies led to fragmented and reduced overall sleep. In essence, the fruit flies tossed and turned in their sleep. But, the flies with reduced 5HT1B and 5HT2 receptor activity displayed no change in their sleeping pattern. Penn researchers were able to treat the fruit flies to a good night's sleep by administering serotonin to the adult mushroom bodies.

The finding that serotonin plays a role in increasing sleep in fruit flies offers hope for the future of therapeutics for sleep disorders. "Serotonin may also promote sleep in humans," suggests Sehgal. "This may explain why serotonin-increasing antidepressants increase sleep."

Future work by Sehgal's lab will attempt to look for a connection among sleep, serotonin, and learning, and memory, while looking deeper into the cellular and molecular activity that enables mushroom bodies to regulate sleep.

New Insights into Working Memory Mechanism

Thu, 01 Jun 2006 13:14:37 PST

( from http://www.rxpgnews.com ) Memory tests performed with amnesiacs have enabled researchers to refute a long-held belief in an essential difference between long-and short-term memories. In the study, researchers from the University of Pennsylvania determined that the hippocampus -- a seahorse shaped structure in the middle of the brain -- was just as important for retrieving certain types of short-term memories as it is for long-term memories.

Their findings, published in the Journal of Neuroscience, overturn the established view of the hippocampus and offers insight on how the brain forms and recalls memories by piecing together related bits of experiences.

"For over 40 years, the chief paradigm has been that the hippocampus was important for creating long-term memory but not short-term or working memory," said Ingrid Olson, a member of Penn's Department of Psychology and researcher at Penn's Center for Cognitive Neuroscience. "However, our data show that one type of working memory, working memory for the relationship between bits of information, is dependent on the hippocampus.

According to Olson, how much time has elapsed or, in other words, the age of the memory -- is less important to the hippocampus than is the requirement to form connections between pieces of information to create a coherent episode of memory.

"I can remember what my keys look like, and I can remember where the coffee table is located, but the critical test of my memory is if I can remember that I left my keys on the coffee table," Olson said.

To study the role of the hippocampus in forming short-term memories, Olson and her colleagues used visual memory tests to study the ability of nine amnesiacs to recall images presented to them on a screen. These subjects all suffered from damage to their hippocampi and related brain structures, and their lives are ruled by the fact that they can no longer form long-term memories, much like characters from the movies "Memento" or "Finding Nemo."

The task required amnesiacs and controls to remember three objects, locations or objects in locations over delays of one or eight seconds. The results show that working memory for objects or locations alone was at normal levels, but that memory for object-location conjunctions was severely impaired at eight-second delays.

"While 'long-term' memory and 'short-term' memory have been useful distinctions for us, they may not exist in the same way for the brain," Olson said.

The researchers believe that a more useful distinction would be between feature memory and conjunction memory the ability to remember specific things versus how they are related. In that regard, the hippocampus serves like the brain's switchboard, piecing individual bits of information together in context.

"The hippocampus is another part of our evolving view of the nature of memories and consciousness," Olson said. "Our memories are not the static, permanent things we would like to think and, even in healthy people, these connections can erode or become muddled, leading to false memories or illnesses like post-traumatic stress disorder."

Dysbindin-1 gene (DTNBP1) - The Intelligence Gene

Sun, 30 Apr 2006 23:09:37 PST

( from http://www.rxpgnews.com ) Psychiatric researchers at The Zucker Hillside Hospital campus of The Feinstein Institute for Medical Research have uncovered evidence of a gene that appears to influence intelligence. Working in conjunction with researchers at Harvard Partners Center for Genetics and Genomics in Boston, the Zucker Hillside team examined the genetic blueprints of individuals with schizophrenia, a neuropsychiatric disorder characterized by cognitive impairment, and compared them with healthy volunteers.

They discovered that the dysbindin-1 gene (DTNBP1), which they previously demonstrated to be associated with schizophrenia, may also be linked to general cognitive ability.

"A robust body of evidence suggests that cognitive abilities, particularly intelligence, are significantly influenced by genetic factors. Existing data already suggests that dysbindin may influence cognition," said Katherine Burdick, PhD, the study's primary author. "We looked at several DNA sequence variations within the dysbindin gene and found one of them to be significantly associated with lower general cognitive ability in carriers of the risk variant compared with non-carriers in two independent groups."

The study involved 213 unrelated Caucasian patients with schizophrenia or schizoaffective disorder and 126 unrelated healthy Caucasian volunteers. The researchers measured cognitive performance in all subjects. They then analyzed participants' DNA samples. The researchers specifically examined six DNA sequence variations, also known as single nucleotide polymorphisms (SNPs), in the dysbindin gene and found that one specific pattern of SNPs, known as a haplotype, was associated with general cognitive ability: Cognition was significantly impaired in carriers of the risk variant in both the schizophrenia group and the healthy volunteers as compared with the non-carriers.

"While our data suggests the dysbindin gene influences variation in human cognitive ability and intelligence, it only explained a small proportion of it -- about 3 percent. This supports a model involving multiple genetic and environmental influences on intelligence," said Anil Malhotra, MD, principal investigator of the study.

The specific role of dysbindin in the central nervous system is unknown, but it is highly present in key brain regions linked to cognition, including learning, problem solving, judgment, memory and comprehension. Scientists speculate that dysbindin plays a role in communication between brain cells in these regions and helps promote their survival. An alteration in the genetic blueprint for dysbindin may ultimately interfere with cell communication and fail to protect brain cells from dying, with a resulting negative impact on cognition and intelligence.

Brains of the smarter kids tend to change more dramatically

Thu, 30 Mar 2006 15:02:37 PST

( from http://www.rxpgnews.com ) Brains of the smarter kids tend to change more dramatically as they grow up, say scientists who claim to have discovered why some children have higher IQ levels.

Scientists led by Philip Shaw at the US National Institute of Mental Health and McGill University in Montreal, Canada, studied 307 children and teenagers between the ages of five and 19 using imaging machines to track growth in the part of the brain that helps a person think.

Using the Wechsler intelligence scale, the children were grouped according to superior, high and average intelligence.

The study found that the brains tissue in children with the highest IQ levels starts out thinner, then thickens more quickly and for a longer time than in their peers, the researchers said.

The findings, along with previous research in animals, suggest intelligence is linked to a complex sculpting or fine-tuning of the brain as a child develops, Shaw said.

'From animal studies, there is some suggestion that there is a process of 'use it or lose it' as the brain matures. Perhaps this is happening particularly efficiently in the most intelligent children,' he said.

Scientists need to do more research before they understand what causes that development. 'We have no idea what's happening at the level of the cell that's driving all of the changes.'

Memory - Retention Begins While You're Still Awake

Wed, 29 Mar 2006 06:32:37 PST

( from http://www.rxpgnews.com ) There's some unwritten law of stadium parking that says after any event some fraction of hapless souls must perform an embarrassing reenactment of Dude, Where's My Car? It might seem like a simple thing to remember until you consider that the brain must often process and retain new memories while simultaneously tending to several unrelated cognitive tasks. Though it's not exactly clear how the brain processes a recent memory, evidence suggests that a good nap during an event might prevent parking mishaps. Many studies have shown that brain regions activated while learning a task are reactivated during sleep, suggesting that this offline processing facilitates memory retention. But when does the memory consolidation process begin?

Studies in rodents and monkeys have shown that the same neuron ensembles activated during the practice phase of a task continue to be activated for several minutes immediately after exposure to a new task. This suggests that delayed activation in the brain represents a step in the memory storage process.

In a new study, Phillippe Peigneux, Pierre Orban, Pierre Maquet, and their colleagues used functional magnetic resonance imaging to test this possibility and probe the fate of recent memories in the human brain. The researchers asked individuals to perform two separate tasks associated with different memory systems, and found that regional brain activity associated with learning a task persisted and evolved while participants completed an unrelated task. The learning-dependent changes in regional brain activity they observed while individuals were awake echoed those seen during sleep. This offline activity may act as a placeholder, maintaining newly acquired information until it gets transferred to long-term storage during the memory consolidation process.

The researchers chose spatial and procedural tasks that are known to induce post-training brain activity in learning-related sectors during sleep. Each task engages a different brain sectorthe spatial task depends on the hippocampus while the procedural task relies on cortical and subcortical regionsallowing the researchers to distinguish each task's post-training brain activity from activity associated with practicing a different task.

For the spatial task, participants navigated a path through virtual space; for the procedural task, they indicated under which of four position markers a dot appeared by rapidly pressing a keystroke. For the unrelated oddball task, participants lay in the scanner and mentally counted the deviant sounds embedded in a monotonous soundtrack. These oddball sessions occurred immediately before a taskproviding baseline brain activityimmediately after a 30-minute training session, and again after a 30-minute rest period. A short behavioral test followed the last oddball session, then participants were scanned a fourth time while performing their task to identify brain regions associated with each task. Two weeks later, individuals were tested on the alternate task, so the researchers could compare post-training modulated brain activity associated with each task.

Brain responses to the oddball task were significantly higher immediately after training on the spatial task than they were in the pre-training session. Delayed post-training activation (after the break) also remained significantly higher in the hippocampus and other brain regions associated with spatial navigation. The pattern for the procedural task was similar but followed a different time course. Brain activity in cortical and subcortical regions associated with task performance decreased immediately after training but then showed a delayed increase, above pre-training levels, in learning-related brain sectors.

For both tasks, modulated offline activity showed a tighter coupling with other brain regions associated with learning each task following the training period; this coupling occurred immediately after training for the spatial task and after a 45-minute delay for the procedural task. The researchers went on to relate these post-training, task-dependent, regionally specific changes to post-training performance.

The relationship between behavioral performance and functionally significant brain activity changes suggests that this offline activity plays a role in maintaining and processing newly acquired memories. Moreover, the researchers argue, these neural correlates of memory maintenancepersistent and reorganized neural activity that occurs while you're alert and tending to other mattersoperate in different brain regions at different times to process distinct types of memories. It remains to be seen whether persistent neural traces continue after memories are consolidated. So you may not need that nap to remember where you parked your car after allbut it wouldn't hurt to jot down the location, just in case.

Strategies help keep memory fit - Research

Wed, 08 Mar 2006 21:49:37 PST

( from http://www.rxpgnews.com ) Believing that you can retain a good memory even in your twilight years is the first step to achieving that goal. Those who believe they can control their memory are more likely to employ mnemonic strategies that help keep memory fit despite the march of time.

The study demonstrates a link between actual cognitive functioning and a low sense of control, and examines whether the relationship between control beliefs and memory performance varies for young, middle-aged, and older adults and whether using mnemonic strategies influences memory performance.

"One's sense of control is both a precursor and a consequence of age-related losses in memory," says lead author Margie Lachman, professor of psychology and director of the Lifespan Lab at Brandeis University. "Our study shows that the more you believe there are things you can do to remember information, the more likely you will be to use effort and adaptive strategies and to allocate resources effectively, and the less you will worry about forgetting."

Funded by the National Institute on Aging, the study involved 335 adults, ages 21 to 83, who were asked to recall a list of 30 categorizable words, such as types of fruit and flowers. Middle-aged and older adults who perceived greater control over cognitive functioning were more likely to categorize the words and had better recall performance, Lachman notes.

"It's no surprise that age-related losses or lapses in memory can challenge our deeply embedded sense of control," says Lachman. "Thus, we find an increase with age in beliefs that memory declines are an inevitable, irreversible, and uncontrollable part of the aging process. These beliefs are detrimental because they are associated with distress, anxiety, and giving up without expending the effort or strategies needed to support memory."

In fact, even young people have problems with memory performance, though they typically chalk it up to distraction or other external factors. In contrast, older adults are more likely to judge their forgetfulness an inevitable fact of aging or even a warning sign of Alzheimer's disease, leading to anxiety and despair.

Those who don't use adaptive strategies for remembering often have the expectation that there is nothing they can do to improve memory. The study's results suggest that interventions that target conceptions of control over memory could be effective for improving strategy use and enhancing memory in middle and later adulthood.

Learning and memory stimulated by gut hormone

Thu, 23 Feb 2006 12:12:37 PST

( from http://www.rxpgnews.com ) Researchers at Yale School of Medicine have found evidence that a hormone produced in the stomach directly stimulates the higher brain functions of spatial learning and memory development, and further suggests that we may learn best on an empty stomach.

Published in the February 19 online issue of Nature Neuroscience by investigators at Yale and other institutes, the study showed that the hormone ghrelin, produced in the stomach and previously associated with growth hormone release and appetite, has a direct, rapid and powerful influence on the hippocampus, a higher brain region critical for learning and memory.

The team, led by Tamas L. Horvath, chair and associate professor of the Section of Comparative Medicine at Yale School of Medicine, and associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, and Neurobiology, first observed that peripheral ghrelin can enter the hippocampus and bind to local neurons promoting alterations in connections between nerve cells in mice and rats. Further study of behavior in the animals showed that these changes in brain circuitry are linked to enhanced learning and memory performance.

Because ghrelin is highest in the circulation during the day and when the stomach is empty, these results also indicate that learning may be most effective before meal-time.

"Based on our observations in animal models, a practical recommendation could be that children may benefit from not overeating at breakfast in order to make the most out of their morning hours at school," said Horvath. "The current obesity epidemic among American school children, which to some degree has been attributed to bad eating habits in the school environment, has been paralleled by a decline of learning performance. It is however too early to speculate if hormonal links between eating and learning are involved in that phenomenon."

Horvath said that high ghrelin levels or administration of ghrelin-like drugs could also protect against certain forms of dementia, because aging and obesity are associated with a decline in ghrelin levels and an increased incidence of conditions of memory loss like Alzheimer's disease.

How memory is stored at the level of neurons

Sun, 19 Feb 2006 17:22:37 PST

( from http://www.rxpgnews.com ) Researchers from The University of Texas at Austin studying electric fish have gained new insight into how memory is stored at the level of neurons.

Their finding, published in the Feb. 16 issue of Neuron, could help researchers better understand memory formation and neural disorders like epilepsy in humans.

Dr. Harold Zakon, Dr. Jörg Oestreich and colleagues show that when electric fish zap each other in dark waters, their neurons store a memory of the sizzling communiqué by turning on special cell membrane channels.

The channels give the fish neurons the ability to retain a memory long after its original stimulus is gone.

"There is short-term stimulation that results in long-term changes in excitability," says Zakon, professor of neurobiology. "Essentially, it is memory."

The electric fish studied by Zakon and Oestreich discharge electrical signals to survey their environment and communicate with each other.

"Every time they discharge, it's kind of like they are opening their eyes and closing them," says Zakon. "Each pulse of electricity is a snapshot of the environment. These guys are swimming around and discharging at a very regular frequency. They're digitizing their environment."

But a problem occurs when the fish are close to each other. They can jam each other's electrical signals. In response, one of the fish will jump to a higher frequency to avoid the jamming signal, emitting more electrical pulses per second than its neighbor.

Oestreich and Zakon found that once the jamming avoidance has started, the fish's neurons continue to discharge at a higher frequency, even after its neighbor fish may have swum away.

The researchers discovered that the neurons' memory was not caused by increased flow of glutamate to their synapses. Glutamate is the major excitatory neurotransmitter in the nervous system and is involved in the processes of learning and memory. They blocked glutamate and found that it did not affect the memory of the neurons.

Instead, the glutamate sets off a cascade of events in the neuron that results in the activation of ion channels, called TRP channels, which then remain active for a long time.

"The long-term activation of these TRP channels," says Zakon, "is the 'memory.'"

Zakon, Oestreich and colleagues don't yet understand how the stimulus leads to the long-lasting activation of the TRP channel. They are pursuing further studies.

"We're looking at the general idea that we have long-term changes in the brain that affect the computation that neurons do," says Zakon. "We have ion channels [in the neurons] and we know those are activated. The mystery is how a short stimulus leads to such a long-lasting activation of the TRP receptor."

Age-related memory improvement linked with consumption of apple products

Tue, 24 Jan 2006 23:47:37 PST

( from http://www.rxpgnews.com ) "An apple a day" now has new meaning for those who want to maintain mental dexterity as they age. New research from the University of Massachusetts Lowell suggests that consuming apple juice may protect against cell damage that contributes to age-related memory loss, even in test animals that were not prone to developing Alzheimer's disease and other dementias.

"This new study suggests that eating and drinking apples and apple juice, in conjunction with a balanced diet, can protect the brain from the effects of oxidative stress and that we should eat such antioxidant-rich foods," notes lead researcher Thomas B. Shea, Ph.D., director of the University of Massachusetts Lowell's Center for Cellular Neurobiology and Neurodegeneration Research, whose study was just published in the latest issue of the Journal of Alzheimer's Disease. Although more research is needed, Shea is excited about these brain health findings, which are encouraging for all individuals who are interested in staying mentally sharp as they age.

Using a well-established animal protocol, Shea and his research colleagues assessed whether consumption of apple juice was protective against oxidative brain damage in aging mice, damage that can lead to memory loss. "These newer findings show that there is something in apples and apple juice that protects brain cells in normal aging, much like the protection we previously saw against Alzheimer-like symptoms," says Shea.

The researchers evaluated adult and aged mice using a standard diet, a nutrient-deficient diet, and a nutrient-deficient diet supplemented with apple juice concentrate in drinking water. Although the adult mice tested were not affected negatively by the deficient diets, the aged mice were, which is consistent with normal aging due to oxidative neurodegeneration. The effect on cognition among the aged mice was measured through well-established maze tests, followed by an examination of brain tissue. However, the aged mice who consumed the diets supplemented with apple juice performed significantly better on the maze tests and all had less oxidative brain damage than those on the standard diet.

Supplementation by apple juice fully protected the aged mice from the oxidative stress caused by the nutrient-deficient diet. In addition, stronger mental acuity resulted when the aged mice consumed the human equivalent of 2-3 cups of apple juice or approximately 2-4 apples per day. "We believe that this effect is due to the apple's naturally high level of antioxidants," states Shea. Previous research with his colleagues also determined that it is not the sugar and energy content of the apple juice, but the antioxidant attributes of apple juice that are responsible for the positive effects.

Activation of protein kinase A (PKA) solidifies fear memory in the brain

Tue, 24 Jan 2006 23:37:37 PST

( from http://www.rxpgnews.com ) When activated, a specific protein in the brain enhances long-term storage of fearful memories and strengthens previously established fearful memories, Yale School of Medicine researchers report this week in Nature Neuroscience.

"This report is the first to demonstrate evidence of enhancements in memory reconsolidation in the brain," said the senior author, Jane Taylor, associate professor in the Department of Psychiatry. "Understanding these molecular mechanisms may provide critical insights into psychiatric disorders."

She said recent data suggest that memories can continue to be changed or eliminated long after they have been formed, or consolidated. Based on findings that suggest memories are susceptible to loss after retrieval, a mechanism that is required to maintain and place back memories into long-term storage has been proposed, Taylor said.

"This 'reconsolidation' process is supported by studies suggesting that disruption of cellular functions known to be required for memory storage after retrieval of a memory can cause a specific loss of that memory," she said.

Taylor and her colleagues found that within the amygdala, a brain region known to be critically involved in the creation and storage of fearful memories, selective activation of protein kinase A (PKA) is sufficient to enhance memory reconsolidation and strengthen a previously established fearful memory. Conversely, inhibiting PKA in the amygdala disrupted memory reconsolidation.

"These findings show bidirectional behavioral plasticity after memory retrieval," Taylor said. "Moreover, we find that amygdalar PKA activation does not affect other memory processes after retrieval, including extinction of fear memory, further showing that our findings are specific for a reconsolidation process."

She said enhancement of reconsolidation may contribute to the development of maladaptive memories in psychiatric disorders such as post-traumatic stress disorder, depression and drug addiction.

"Additionally, the ability to strengthen memories by retrieval has important implications for psychotherapies," she said.

Working memory retains visual details despite distractions

Sat, 21 Jan 2006 21:59:37 PST

( from http://www.rxpgnews.com ) The ability to retain memory about the details of a natural scene is unaffected by the distraction of another activity and this information is retained in "working memory" according to a study recently published in Journal of Vision, an online, free access publication of the Association for Research in Vision and Ophthalmology (ARVO). These results reinforce the notion that humans maintain useful information about previous fixations in long-term working memory rather than the limited capacity of visual short-term memory (VSTM).

Memory has traditionally been divided into VSTM and long-term memory (LTM). VSTM usually involves the retention of about four objects at a time. This is followed by either information loss or the transfer of this information into LTM. This study provides further evidence that an intermediary "working memory" better describes the nature of information retained while engaged in a particular task.

In the study conducted by Oxford Brookes University Professor David Melcher, participants were asked to view a photograph of a natural scene for 10 seconds. Following the initial viewing, they were asked to silently read a paragraph for 60 seconds, repeating if necessary, or view an image with five colored square for 60 seconds. The participants were then asked questions about the first scene they had viewed. The results show that the addition of the reading task had no measurable influence on the average performance for either color, shape or location questions compared to other trials which involved just a 10-second delay between the viewing and the testing.

According to Melcher, "These results provide further evidence that visual scenes are special and that memory for real scenes involves a system with different properties than that used for words or simple shapes. We are currently examining how this memory system develops in children, how it is affected by aging and how it interacts with attention and disorders of attention."

Sugared drinks can boost memory retention

Thu, 19 Jan 2006 15:37:37 PST

( from http://www.rxpgnews.com ) Sugared drinks can help boost memory retention and combat dementia, a study has found.

Researchers led by Leigh Riby from Glasgow Caledonian University, Scotland, focused on an area of the brain known as the hippocampus, which creates new memories but declines with the onset of dementia, a memory disorder in older people.

They studied 25 volunteers aged between 18 and 52 years and asked them to remember a list of words. The researchers used a series of memory tests and brain-imaging techniques to assess how volunteers responded after guzzling sugary drinks, reported the online edition of Daily Mail.

Those that drank orange-flavoured water containing 25g of sugar, about the same as a can of Coca-Cola, could remember 11 percent more words. If the participants consumed twice that amount of sugar, they showed a 17 percent improvement, the researchers said.

They were also around 100 milliseconds faster at remembering sets of letters shown to them a few minutes earlier.

Riby contented: "Our research shows that consuming a glucose drink can significantly boost memory recall."

The researchers found the hippocampus lit up with activity after participants had a sweetened drink and they were able to recall 17 percent more than without a drink.

"It is widely accepted that when humans face a stressful situation they experience a natural rise in glucose in the body, particularly in the hippocampus," Riby said.

"They also tend to remember these dangerous or scary occurrences more clearly than other memories.

"This glucose-memory system has evolved to help humans survive. Unfortunately, it is compromised in old age."

"What's more, our work on young and middle aged adults shows if we can 'train' our bodies early in life to effectively use their own glucose reserves, poor memory function can be minimised in adulthood."

Memory retrieval is a form of mental time travel

Tue, 27 Dec 2005 17:26:38 PST

( from http://www.rxpgnews.com ) Neuroscientists at Princeton University have developed a new way of tracking people's mental state as they think back to previous events -- a process that has been described as "mental time travel."

The findings, detailed in the Dec. 23 issue of Science, will aid efforts to learn more about how people mine the recesses of memory and could have a wide-ranging impact in the field of neuroscience, including studies of brain disorders such as Alzheimer's disease.

The researchers showed nine participants a series of pictures and then asked them to recall what they had seen. By applying a computerized pattern-recognition program to brain scanning data, the researchers were able to show that the participants' brain state gradually aligned with their brain state from when they first studied the pictures. This supports the theory that memory retrieval is a form of mental time travel.

In addition, by measuring second-by-second changes in how well participants were recapturing their previous brain state, the researchers were able to predict what kind of item the subjects would recall next, several seconds before they actually remembered that item.

The study was conducted by Kenneth Norman, an assistant professor of psychology, and Sean Polyn, who earned his Ph.D in psychology from Princeton in 2005 and is a now a postdoctoral researcher at the University of Pennsylvania. Polyn and Norman collaborated with Jonathan Cohen, director of Princeton's Center for the Study of Brain, Mind and Behavior, and Vaidehi Natu, a researcher in Norman's lab.

"When you try to remember something that happened in the past, what you do is try to reinstate your mental context from that event," said Norman. "If you can get yourself into the mindset that you were in during the event you're trying to remember, that will allow you to remember specific details. The techniques that we used in this study allow us to visualize from moment to moment how well subjects are recapturing their mindset from the original event."

In the experiment, participants studied a total of 90 images in three categories -- celebrity faces, famous locations and common objects -- and then attempted to recall the images. Norman and his colleagues used Princeton's functional magnetic resonance imaging (fMRI) scanner to capture the participants' brain activity patterns as they studied the images. They then trained a computer program to distinguish between the patterns of brain activity associated with studying faces, locations or objects.

The computer program was used to track participants' brain activity as they recalled the images to see how well it matched the patterns associated with the initial viewing of the images. The researchers found that patterns of brain activity for specific categories, such as faces, started to emerge approximately five seconds before subjects recalled items from that category -- suggesting that participants were bringing to mind the general properties of the images in order to cue for specific details.

"What we have learned over the years is that what you get out of memory depends on how you cue memory. If you have the perfect cue, you can remember things that you had no idea were floating around in your head," Norman said. "Our method gives us some ability to see what cues participants are using, which in turn gives us some ability to predict what participants will recall. We are hopeful that, in the long run, this kind of work will help psychologists develop better theories of how people strategically cue memory, and also will suggest ways of making these cues more effective.

Brain size matters for intellectual ability

Fri, 23 Dec 2005 18:52:38 PST

( from http://www.rxpgnews.com ) Brain size matters for intellectual ability and bigger is better, McMaster University researchers have found.

The study, led by neuroscientist Sandra Witelson, a professor in the Michael G. DeGroote School of Medicine, and published in the December issue of the journal Brain, has provided some of the clearest evidence on the underlying basis of differences in intelligence.

The study involved testing of intelligence in 100 neurologically normal, terminally ill volunteers, who agreed that their brains be measured after death.

It found bigger is better, but there are differences between women and men.

In women, verbal intelligence was clearly correlated with brain size, accounting for 36 percent of the verbal IQ score. In men, this was true for right-handers only, indicating that brain asymmetry is a factor in men.

Spatial intelligence was also correlated with brain size in women, but less strongly. In men, spatial ability was not related to overall brain size. These results suggest that women may use verbal strategies in spatial thinking, but that in men, verbal and spatial thinking are more distinct.

It may be that the size or structure of the localized brain regions which underlie spatial skills in men is related to spatial intelligence, as was shown in previous research in Witelson's lab on the brain of Albert Einstein.

In a further sex difference, brain size decreased with age in men over the age span of 25 to 80 years, but age hardly affected brain size in women. It is not known what protective factors, which could be genetic, hormonal or environmental, operate in women.

It remains to be determined what the contribution of nature and nurture are to this cerebral size relationship with intelligence, Witelson said. She added that the results point to the need for responsibility in considering the likely future use of magnetic imaging (or MRIs) of brain structure as a measure of ability in student and workforce settings.

"We're going to need to be careful if, in the future, we use MRI brain scans as a measure of ability in any selection process," she said.

New Research on Mental Time Travel

Fri, 23 Dec 2005 15:59:38 PST

How brain replenishes memory-making molecules

Thu, 22 Dec 2005 04:59:38 PST

( from http://www.rxpgnews.com ) New research on living neurons has clarified how the brain refreshes the supply of molecules it needs to make new memories.

The discovery by scientists at UCSF is reported today in the December 22 issue of the journal Neuron and is featured on the journal's cover.

Memory formation is thought to involve a strengthening of the communication between neurons in the part of the brain known as the hippocampus. Researchers know that this increased communication results from a surge in the number of receptors on one neuron that is available to bind to the neurotransmitter glutamate released from another neuron. The two neurons meet at a synapse.

But how and from where the brain gains fresh supplies of these crucial receptors has remained unclear. Known as AMPA receptors, they are essential for the rapid connections made between nerves during learning.

The scientists sought to answer this question by studying the basal trafficking of receptors -- the normal process by which receptors are replaced from fresh stores that are synthesized and located inside the cell. Focusing on live neurons cultured from rats, they discovered clear evidence to dispel the prevailing view that receptors at the synapse are constantly being replaced by stores inside the cell. Rather, the scientists found that the synaptic receptors are relatively stable, lasting about 16 hours before they are replaced.

The study also supports an unsuspected route by which new receptors make their way to the synapse: Fresh AMPA receptors appear to be placed on the cell surface at the cell body and then migrate along the arms or dendrites of the cell to synapses, rather than moving within the cell to the synapse as had been thought.

The scientists suspect the trafficking process their research revealed also occurs during learning and memory formation, but at a much faster rate. The study may provide insight into how to treat memory disorders, said Pam England, PhD, assistant professor of pharmaceutical chemistry at UCSF and senior author on the study.

A number of studies have suggested that synaptic AMPA receptors are constantly and rapidly being replaced by receptors from inside the cell to permit rapid regulated changes in the number of receptors, England explained. "Our study suggests that the source of increased receptors during learning or memory formation is probably from receptors traveling along the neuron surface."

The team used a novel molecule to selectively "silence" AMPA receptors on the neuron surface and show that receptors inactivated at synapses were not rapidly replenished by receptors inside the cell, as had been thought.

The silencing molecule, known as ANQX, is activated by exposure to brief pulses of ultraviolet light, so the scientists could shine light on neurons treated with ANQX and inactivate AMPA receptors on the neuron surface. Researchers then could use continuous electrophysiological recordings to measure the "recovery" - or replacement -- of these inactive AMPA receptors with fresh ones, as evidence by restored electric current through the receptors.

An image of a neuron used to study how the brain acquires fresh supplies of memory-making molecules.

The use of a light-activated silencer allowed the team to study naturally occurring receptors, rather than genetically modified receptors, which might not traffic normally.

"This way, we could study the effect on the neuron before, during and after inactivating the receptors," England said. "This is a direct, quantitative measure of native AMPA receptor trafficking in real time."

The scientists hope to next study AMPA receptor trafficking in response to increased neuronal activity, in order to provide more insight into the mechanism underlying learning and memory.

Lead author on the paper is Hillel Adesnik, BS, a neuroscience graduate student in the cellular and molecular pharmacology department at UCSF working in the laboratory of Roger Nicoll, MD, professor in the department and co-corresponding author on the paper.

Amnesiac gene mediates in memory trace formation

Mon, 05 Dec 2005 06:14:38 PST

( from http://www.rxpgnews.com ) Memory formation follows a dynamic pattern, allowing for retrieval from different areas of the brain, depending on when an organism needs to remember, said a researcher at Baylor College of Medicine.

That is what Dr. Ron L. Davis, professor of molecular and cellular biology at BCM, theorizes, based on his most recent report on the topic that finds a memory trace in Drosophila or fruit flies is formed in a pair of neurons called the dorsal pair medial neurons, but only 30 minutes after the fact and only through the mediation of a gene called, ironically, amnesiac. (A memory trace is a chemical change in tissue that represents the formation of a memory.) The study appears in the current issue of the journal Cell.

Davis and his colleagues were one of the first to actually record a memory trace being formed. That one was first stored in the insect's antennal lobe (where odors are processed). The flies are trained to associate an odor with an electric shock. The change in these neurons was immediate, but lasted only five to seven minutes.

In the more recent report involving the DPM neurons, the change can be seen 30 minutes after the formation of the memory, but it lasts about two hours.

"The other intriguing thing we don't understand is that this occurs only in one branch of the DPM neuron," said Davis. "Our impression now is that maybe what guides the behavior after training in the first few minutes is the antennal lobe. That is the important part that guides behavior for the small window of time after training. The DPM neurons have that role from 30 minutes to two hours."

The finding belies the commonly held precept that a memory is formed in the same way that data are stored in a computer â always in the same place.

"It's not as if we are forming memories that are then being written to a "hard disk" area of the brain, and it's there and recalled from the same location at any time after learning," said Davis. "We now think that different areas of the brain have dominion over small intervals of time after training. One area might have dominion and then another." Others who participated in the research include Drs. Dinghui Yu and Anjana Srivatsan, both of BCM, and Scott Waddell and graduate student Alex Keene, of the University of Massachusetts Medical Center.

Memory formation follows a dynamic pattern

Fri, 02 Dec 2005 20:21:38 PST

( from http://www.rxpgnews.com ) Memory formation follows a dynamic pattern, allowing for retrieval from different areas of the brain, depending on when an organism needs to remember, said a researcher at Baylor College of Medicine.

That is what Dr. Ron L. Davis, professor of molecular and cellular biology at BCM, theorizes, based on his most recent report on the topic that finds a memory trace in Drosophila or fruit flies is formed in a pair of neurons called the dorsal pair medial neurons, but only 30 minutes after the fact and only through the mediation of a gene called, ironically, amnesiac. (A memory trace is a chemical change in tissue that represents the formation of a memory.) The study appears in the current issue of the journal Cell.

Davis and his colleagues were one of the first to actually record a memory trace being formed. That one was first stored in the insect's antennal lobe (where odors are processed). The flies are trained to associate an odor with an electric shock. The change in these neurons was immediate, but lasted only five to seven minutes.

In the more recent report involving the DPM neurons, the change can be seen 30 minutes after the formation of the memory, but it lasts about two hours.

"The other intriguing thing we don't understand is that this occurs only in one branch of the DPM neuron," said Davis. "Our impression now is that maybe what guides the behavior after training in the first few minutes is the antennal lobe. That is the important part that guides behavior for the small window of time after training. The DPM neurons have that role from 30 minutes to two hours."

The finding belies the commonly held precept that a memory is formed in the same way that data are stored in a computer - always in the same place.

"It's not as if we are forming memories that are then being written to a "hard disk" area of the brain, and it's there and recalled from the same location at any time after learning," said Davis. "We now think that different areas of the brain have dominion over small intervals of time after training. One area might have dominion and then another."

Synchronized Brain Interactions Associated with Memory and Decision-Making

Tue, 15 Nov 2005 19:38:38 PST

( from http://www.rxpgnews.com ) Next time you lose your keys, you might consider the Clark's nutcracker. During the fall, this woodland resident collects over 30,000 seeds, buries them in discrete locations, then returns over the winter to retrieve its cache. This improbable behavior requires the coordinated activity of different brain structures to integrate spatial coordinates encoded in the hippocampus with memories of how to find the seed stash. As it turns out, food-storing birds have a significantly larger hippocampusâa brain region involved in spatial organization and memoryâthan nonhording species.

In the laboratory, rats learning maze tasks also rely on hippocampal spatial information, which the prefrontal cortex integrates with memory of the route, task rules, and other relevant cues to direct navigational decisions. How the brain coordinates this activity is an active area of research. When neuron populations fire in sync, they produce oscillations in brain wave patterns (measured as local field potentials) that operate at many different frequencies. Brain wave frequencies called theta rhythms, which are prevalent in the rat hippocampus, are associated with working memory and decision-making in both animals and humans. Theta rhythmsâwhich oscillate at about eight cycles per secondâappear to act like a metronome for individual neurons that âphase lockâ their firing in time with the theta rhythm.

Whether the synchronized activity of neuron populations across different brain structures correlates with functions like decision-making, and whether phase-locking somehow coordinates these diverse structures has remained an open question. But now, by training rats on a spatial working memory taskânavigating a maze to a food rewardâMatthew Jones and Matthew Wilson demonstrate a clear correlation between coordinated hippocampal and prefrontal cortex activity and memory or decision-making processes.

Jones and Wilson first trained rats on a simple maze task. The maze was shaped like a stretched-out âHâ (see diagram). Rats were trained to shuttle back and forth across the long central arm for about 20 trials per day. At one end of this central arm, a moveable barrier directed the rats to turn either left or right toward a chocolate reward. At the opposite end, rats encountered a free choice at the T-junction: the correct turn (leading to more chocolate) was contingent upon the direction in which they were previously directed by the barrier at the âforced turnâ end of the maze. As rats ran toward this choice point, they therefore had to âhold in mindâ both task rules and information about the preceding forced turn in order to decide upon the correct route. Like the nutcracker, flying from seed stash to seed stash in search of its food, the rats' performance presumably relies upon coordination of spatial information stored in the hippocampus with connected brain regions that guide behavior.

After rats had learned to correctly navigate the maze over 80% of the time for two straight days, they were outfitted with electrodes to search for neurons showing task-related activity. The authors recorded action potentials (activation signals) of groups of individual neurons, and local field potentials, from the medial prefrontal cortex (mPFC), which is associated with working memory and decision-making, and a hippocampal region called CA1 (named after the Egyptian god Ammon's horns, cornu Ammonis in Latin). It has been known since the early seventies that neurons in CA1 show spatially selective activityâthat is, each neuron fires action potentials only in restricted regions of an animal's environment.

Firing rates of individual neurons in both CA1 and mPFC were indeed task-related: they distinguished between the directions of runs across the central arm, and between the different routes between reward points during the choice stages. The firing rates of CA1âmPFC neuron pairs coactivated during central arm crossings showed the highest correlations as rats ran toward the decision point. This correlated activity between the neuron pairs was significantly reduced when rats made mistakes and chose the wrong direction. Such synchronized activity, the authors explain, may represent the transfer of spatial information from the hippocampus to a working memory system in the mPFC.

Jones and Wilson go on to show that many CA1 and mPFC neurons were phase-locked to theta rhythms, with enhanced phase-locking during trials requiring working memory and decision-making. This effectively means that the firing of neurons in both structures was aligned to the same theta rhythm âmetronome.â This, in turn, means that CA1âmPFC activities became correlated during distinct portions of the task. These correlations suggest that, as expected, the coordination and function of different brain regions depends on the task at hand. Additionally, this study shows that theta rhythms can be used as a reference against which to coordinate hippocampal and mPFC activity in accordance with behavioral demands of this maze task. Beyond shedding light on the neurobiology of behavior, these findings suggest that theta rhythms may contribute to diseases that involve disruptions in prefrontal cortex connectivity, such as schizophreniaâwhich, interestingly, can impair the spatial working memory of patients. âLiza Gross

"Sharp" older brains store memories differently than younger brains

Mon, 14 Nov 2005 01:45:38 PST

( from http://www.rxpgnews.com ) Researchers working with rats have found the first solid evidence that still "sharp" older brains store and encode memories differently than younger brains.

This discovery is reported by a Johns Hopkins team in the issue of Nature Neuroscience released online Nov. 13. Should it prove to apply as well to human brains, it could lead eventually to the development of new preventive treatments and therapies based on what healthy older brains are doing, rather than on the less relevant, younger brain model, according to study co-author Michela Gallagher, chair of the Department of Psychological and Brain Sciences at Johns Hopkins' Zanvyl Krieger School of Arts and Sciences.

"We found that aged rats with preserved cognitive abilities are not biologically equivalent to young rats in some of the basic machinery that neurons use to encode and store information in the brain," said Gallagher, who collaborated with Alfredo Kirkwood and Sun Seek Min of Johns Hopkins' Krieger Mind/Brain Institute and Hey-Kyoung Lee, now of the University of Maryland College Park. Lee was a research associate at the Mind/Brain Institute when the research was done.

The Gallagher-Kirkwood team compared the brains of 6-month-old rats with those of 2-year-old (considered "aged") rodents that had performed in the "young" range on various learning tasks. The aged rats' brains also were compared with those of older rats which showed declines in their abilities to learn new things. The researchers were looking at a key set of nerve cell connections that store information by modifying the strength of chemical communications at their synapses. (Synapses are the tiny gaps between nerve cells, where chemicals released by one cell act upon another.) Synaptic communication is the way brains register and preserve information to form memories.

The team found that while the older rats with compromised cognition had brains that had lost the ability to adjust the force of those synaptic communications, the older rats whose memories remained sharp still had that capacity. Interestingly enough, the successful older rats also relied far less than did younger rats on a synaptic receptor that is linked to a common mechanism for storing memories, the team learned.

"Instead, successful agers relied more than young rats on a different mechanism for bringing about synaptic change," Gallagher said. "This 'switch' could serve the same purpose storing memories but through a different neurochemical device."

Neuronal Dendrite Changes Llinked to Learning and Memory

Wed, 02 Nov 2005 13:09:38 PST

( from http://www.rxpgnews.com ) Neurons experience large-scale changes across their dendrites during learning, say neuroscientists at The University of Texas at Austin in a new study that highlights the important role that these cell regions may play in the processes of learning and memory.

The research, published online Oct. 23 and in the November issue of the journal Nature Neuroscience, shows that ion channels distributed in the dendritic membrane change during a simulated learning task and that this requires the rapid production of new proteins.

"Our new work strongly supports the idea that learning involves changes in dendrites," says Dr. Daniel Johnston, director of the Center for Learning and Memory and professor in the Institute for Neuroscience.

The finding could also lead to advances in understanding conditions like epilepsy and age-related memory loss and could point to potential treatment opportunities for such conditions in the future.

Dendrites--the thin branch-like extensions of a neuron cell--receive many inputs from other neurons that transmit information through contact points called synapses. Much attention has been focused on the role that changes at synapses play in learning. They change in ways that make it easier for connected neurons to pass information.

Johnston and his colleagues show that learning and memory are likely to not only involve changes at synapses, but also in dendrites. They found that h-channels, which are distributed throughout the dendrite membrane and allow the passage of potassium and sodium ions into and out of the neuron, are altered during learning.

"The h-channels undergo plasticity, not near the synapse but probably throughout the dendritic tree," says Johnston.

To record the changes during learning, cells from the rat hippocampus (an important area of the brain for short-term memory) were electrically stimulated using a high frequency pattern called theta-bursts. Theta-bursts mimic the electrical stimulus that shoots through neurons when animals perform a learning task. The researchers found that when stimulated with theta-bursts, hippocampus neurons showed h-channel plasticity and a rapid increase in the synthesis of h-channel proteins.

The proteins were produced in the rat hippocampal neurons within 10 minutes, which is pretty rapid for cells, says Johnston.

"This really pushes the envelope with respect to how fast a neuron can produce new proteins important for learning," he says.

Learning and memory researchers know that protein synthesis in neurons is related to long-term memory, because protein synthesis inhibitors block long-term memory in animals.

Johnston says it's possible that the new proteins are being used by the neuron to build more h-channels in the dendrite membrane. He has a working hypothesis that h-channels may help buffer receiving neurons from being barraged and over-stimulated by inputs coming from information transmitting neurons.

"The h-channel plasticity alters the way the entire dendritic tree responds to the synaptic inputs," he says.

H-channel plasticity may normalize the firing rate of the cell.

"If cells aren't kept in a normal operating regime, learning would not be as effective," Johnston says. "H-channel plasticity might keep the cell within an operating window in which it can continue to learn."

Impaired Olfactory Memory by Spatially Controlled Switch of AMPA Receptors

Tue, 18 Oct 2005 12:10:38 PST

( from http://www.rxpgnews.com ) The smell of baking bread, the perfume of flowers, the tang of sea airyour nose can sense and distinguish between these smells and thousands more. The sense of smellmanaged by the olfactory systemis a crucial tool for sensing the environment. Thousands of low molecular weight molecules bind to a vast repertoire of odor receptors on olfactory sensory neurons in the nose. These neurons extend long projections into an area of the forebrain known as the olfactory bulb, where chemical messengers (neurotransmitters) pass on information to other neurons elsewhere in the brain. In ways that are only just beginning to be understood, all this information is integrated by neural circuits in the brain so that different odors can be learned and discriminated; in addition, changes in neuron activity are responsible for remembering odors.

The neural circuits that underlie odor learning and discrimination and olfactory memory rely on neurotransmission that is mediated by ion channels (pores that allow ions to pass through the normally impermeable cell membrane) called γ-amino-3hydroxy-5methyl-4isoxazoleproprionate receptors (AMPARs). Each AMPAR is comprised of multiple subunits of glutamate receptors (GluRs), which form the ion channels. Most AMPARs contain GluR-B, which controls many of their properties, including their permeability to calcium ions.

Derya Shimshek, Andreas Schaefer, and their colleagues are combining genetic studies and quantitative behavioral studies to assess how AMPARs contribute to olfactory learning, discrimination, and memory. To investigate these processes, the researchers have constructed two sets of genetically modified mice. In the first set, some neurons in the forebrain express a form of GluR-B that increases the calcium ion permeability of AMPARs. In the second set, GluR-B expression is partially reduced in the forebrain, a manipulation that also renders AMPARs calcium permeable.

In behavioral tests, in which mice were rewarded for their ability to discriminate between similar test odors, genetically altered mice showed quicker olfactory learning and increased discriminatory prowess than mice without genetic alterations in GluR-B. Thus, increased AMPAR-mediated entry of calcium ions into neurons within the forebrain, in particular within the olfactory bulb, seems to enhance olfactory learning and discrimination. By contrast, GluR-B-depleted mice showed impaired odor memory. Different GluR-B-depleted mice had different degrees of memory impairment (even though they all had similar improvements in odor learning and discrimination). This variability, the researchers suggest, could reflect regional differences in the expression of residual GluR-B produced by the genetic manipulations used to derive the mice. When the scientists investigated this idea by measuring GluR-B expression in various areas of the brains of mice whose behavior they had already tested, they found that the decreases in olfactory memory in individual GluR-B-depleted mice strongly correlated with reductions in GluR-B levels in their hippocampus and piriform cortex. Taken together with data from other groups that discounts the involvement of the hippocampus in the type of long-term olfactory memory tested here, this result strongly supports the prevalent view that the piriform cortex is important in olfactory memory.

Overall, the results presented by Shimsek and colleagues suggest that olfactory discrimination and memory in mice are achieved in mechanistically and spatially distinct ways even though the same ion channel receptor is involved. The researchers' experimental approachcombining quantitative behavioral analyses with genetic manipulations that introduce variable patterns of gene expression into the brainshould prove invaluable for dissecting the neural circuitry underlying not only olfaction but also other sensory systems in mice. And because these systems are very highly conserved, finding out about mouse olfaction should also indicate how humans sniff out good and bad smells. Jane Bradbury

Age related memory loss is due to inability to filter distractions

Mon, 12 Sep 2005 20:31:38 PST

( from http://www.rxpgnews.com ) The short-term memory problems that accompany normal aging are associated with an inability to filter out surrounding distractions, not problems with focusing attention, according to a study by researchers at the University of California, Berkeley.

Although older patients often report difficulty tuning out distractions, this is the first hard evidence from functional magnetic resonance imaging (fMRI) studies of the brain that memory failure owes more to interference from irrelevant information than to an inability to focus on relevant information.

"Difficulty filtering out distractions impacts a wide range of daily life activities, such as driving, social interactions and reading, and can greatly affect quality of life," said study leader Dr. Adam Gazzaley, adjunct assistant professor of neuroscience at UC Berkeley and a newly appointed assistant professor of neurology and physiology at UC San Francisco.

"These results reveal that efficiently focusing on relevant information is not enough to ensure successful memory," he said. "It is also necessary to filter distractions. Otherwise, our capacity-limited short-term memory system will be overloaded."

The finding could mean that an inability to ignore distracting information is at the heart of many cognitive problems accompanying aging, Gazzaley said, and suggests that drugs targeting that problem may be more effective at improving memory than drugs that improve focusing ability. He now is exploring the therapeutic role of different medications - including one of the main drugs to treat Alzheimer's disease - in older individuals with suppression deficits.

Because Gazzaley and his colleagues have identified areas of the brain that are markers for focusing and ignoring visual information, fMRI may be a good tool for assessing the value of therapies designed to improve memory and for diagnosing attention and memory problems in young and old, ranging from attention deficit disorder to dementia.

"Is this a unifying mechanism that can account for broader problems regarding attention and memory?" asked coauthor Dr. Mark D'Esposito, UC Berkeley professor of neuroscience and psychology and director of the campus's Henry Wheeler Brain Imaging Center. "I think it explains a lot of it. If you are unable to block out distracting information, you can't really attend to what you are supposed to attend to, you can't get in what you are supposed to remember, and you have a hard time retrieving what you are supposed to remember. Rather than think of it as someone having an attention problem and a memory problem, you can just think of it as someone having one problem - the inability to filter out distracting information - that's affecting other domains such as attention and memory."

Gazzaley, D'Esposito, research assistant Jeffrey W. Cooney and graduate student Jesse Rissman will report their findings in the journal Nature Neuroscience, to be published online Sept. 11.

Gazzaley and his colleagues compared young adults aged 19 to 30 with older adults aged 60 to 77 using a simple memory test that introduced irrelevant information. The tests were conducted while subjects' heads were inside a fMRI scanner so that activity in the brain could be pinpointed.

While young subjects were easily able to suppress brain activity in areas that process information irrelevant to the memory task, older adults on average were unable to suppress such distracting information. Both groups were equally able to enhance brain activity in the areas dealing with information relevant to the task.

Interestingly, six of the 16 older adults had well-preserved short-term memory and no problems ignoring irrelevant information, suggesting that some people are able to avoid memory loss as they age. Gazzaley hopes to find out what makes these people different from the average aging adult.

"Encouragingly, a subgroup of the older population does not experience this suppression deficit and accompanying memory impairment, opening the road for studies of successful aging," Gazzaley said.

Gazzaley, a neurologist who specializes in treating mild cognitive impairment common in older adults, set out to see how attention affects short term or "working" memory. He developed a test to distinguish two aspects of attention: the brain's ability to focus on a visual stimulus, and the ability to suppress or ignore other visual information. He noted that both involve brain activity in the higher level neocortex, acting on the visual cortex - a process he refers to as "top-down modulation."

The test involves presenting a sequence of four images, two of them faces and two natural scenes. Subjects were asked to remember either faces, in which case the scenes were irrelevant information; or scenes, in which case faces were irrelevant. Subjects then were asked whether a particular face or scene appeared among the four images. In a separate test, subjects were asked only to observe the stimuli without attempting to remember them.

After first identifying with the fMRI the regions in the brain attentive to faces and scenes (they differ slightly in each individual), Gazzaley presented his subjects with the three tests and recorded brain images in each case.

When asked to remember faces, young adults showed enhanced activity in the brain area dealing with faces and decreased activity in the area dealing with scenes (the parahippocampal/lingual gyrus). Similarly, when asked to remember scenes, they showed enhanced activity in the scene area of the brain and suppressed activity in the area dealing with faces.

Older adults, however, while showing comparable enhancement of the face area when asked to concentrate on faces, exhibited poor or no suppression of the scene area, and vice versa.

"These data suggest that older individuals are able to focus on pertinent information, but are overwhelmed by interference from failing to ignore distracting information, resulting in memory impairment," the authors wrote.

D'Esposito said that the technique Gazzaley developed to probe focusing and ignoring ability opens the door to numerous experiments that could shed light on a popular theory today - that problems of aging have to do with a decline in the brain's frontal lobe.

"The frontal lobes are the highest level of cognition and the area that integrates information from all over the brain," he said. "If you look at the frontal lobes over time, that is the area where there is more decline than any other part of the brain."

To shed light on this hypothesis, Gazzaley and D'Esposito plan to look at patients with known or presumed frontal lobe damage, to see if they also have problems with focusing or ignoring. Also, they plan to look at people with attention deficit disorder, addiction problems, and mild cognitive impairment in search of evidence that these problems too are due to dysfunction of the frontal lobe.

"There may be unknown lesions in the frontal lobe that affect attention," Gazzaley said. "Aging is not a disease, but I think there likely is a problem with top-down control that could be fixed with drugs."

"If aging is a frontal lobe dysfunction, it is a mild form of it," D'Esposito said. "And if we learn something about it, then we may be able to help and know more about patient populations that have a more severe form of frontal lobe damage, like traumatic brain injury and strokes and dementia."

Da Memory Code, A Neurobiologist's Holy Grail?

Sat, 10 Sep 2005 14:46:38 PST

( from http://www.rxpgnews.com ) While neurobiologists have long hypothesized this type of neural coding, the study presents the first evidence that a "memory code" of any kind may exist. The UCI researchers believe that this code, as well as similar codes that may be discovered, will not only broaden our understanding of normal learning and memory but also may shed light on learning disorders. It may also one day be possible to manipulate these codes to control what and how we remember not only basic sounds, but complicated information and events.

Weinberger and his colleagues found that when the brain uses this coding method, information is stored in a greater number of brain cells, which should result in a stronger memory. However, the researchers believe that if the brain fails to use the code, the resulting memory even if it is an important one would be weaker because fewer neurons would be involved.

"This memory code may help explain both good and poor memory," said Norman Weinberger, a professor of neurobiology and behavior in UCIs Center for the Neurobiology of Learning and Memory. "People tend to remember important experiences better than routine ones."

Weinberger and postdoctoral researcher Richard Rutkowski discovered this coding system through studying how the primary auditory cortex responds to various sounds.

In the study, the researchers trained rats to press a bar to receive water when they heard a certain tone. The tone was varied in its importance to different rats as shown by their different levels of correct performance.

After brain mapping these test rats, the researchers found that the greater the importance of the tone, the greater the area of the auditory cortex that became tuned to it. The results in rats that received the same tones but were trained to a visual stimulus did not differ from those in untrained rats, showing that the behavioral importance of the tone, not its mere presence, was the critical factor.

An increased representation of low frequencies, related to the acoustic spectrum of the reward delivery equipment, also was discovered in both experimental and control trained subjects, supporting the conclusion that behaviorally important sounds gain representational area. Furthermore, there was a surprising reduction in total AI area for the experimental and control groups, compared with untrained naive subjects, indicating that the functional dimensions of AI are not fixed. Overall, the findings support the encoding of acquired stimulus importance based on representational size in AI.

NOTE:
The main stages in the formation and retrieval of memory, from an information processing perspective, are:

* Encoding (processing and combining of received information)
* Storage (creation of a permanent record of the encoded information)
* Retrieval/Recall (calling back the stored information in response to some cue for use in some process or activity)

Translational control of memory by eIF2a kinase GCN2

Tue, 30 Aug 2005 19:57:38 PST

( from http://www.rxpgnews.com ) A group of Montreal researchers has discovered that GCN2, a protein in cells that inhibits the conversion of new information into long-term memory, may be a master regulator of the switch from short-term to long-term memory. Their paper Translational control of hippocampal synaptic plasticity and memory by the eIF2a kinase GCN2, which was published in the August 25th issue of the journal Nature, provides the first genetic evidence that protein synthesis is critical for the regulation of memory formation.

This new discovery is the fruit of an international collaboration. The work of McGill researchers Nahum Sonenberg, Karim Nader, Wayne Sossin and Claudio Cuello, Jean-Claude Lacaille and Nabil Seidah of the Université de Montréal, and David Ron of New York University sheds light on the mysterious workings of the hippocampus, a region of the brain responsible for learning and memory.

"Not all new information we acquire is stored as long-term memory," says Dr. Costa-Mattioli, a post-doctoral fellow in the laboratory of Dr. Sonenberg, who spearheaded the research project. "For example, it takes most people a number of attempts to learn new things, such as memorizing a passage from a book. The first few times we may initially succeed in memorizing the passage, but the memory may not be stored completely in the brain and we will have to study the passage again."

In a series of experiments, the researchers demonstrated that mice bred without the GCN2 protein (known as transgenic mice) acquire new information that does not fade as easily as that of normal mice. This new information is more frequently converted into long-term memory. The researchers concluded that GCN2 may prevent new information from being stored in long-term memory.

Adds Dr.Jean-Claude Lacaille: "The process of switching to long-term memory in the brain requires both the activation of molecules that facilitate memory storage, and the silencing of proteins such as GCN2 that inhibit memory storage."

Although research on humans is still a distant possibility, the scientists believe their discovery may hold promise in the treatment of a variety of illnesses linked to memory. "The discovery of the role of GCN2 in long-term memory may help us develop targeted drugs designed to enhance memory in patients with memory loss due to illnesses such as Alzheimer's disease, where protein synthesis and memory are impaired," concludes Dr. Karim Nader.

Misty Watercolor Memories, Biochemically Speaking

Wed, 24 Aug 2005 04:25:38 PST

( from http://www.rxpgnews.com ) Eyewitness testimony has a unique ability to convince juries. The attorney asks the witness to identify the guilty party. The witness points to the defendant, the crowd gasps, and the judge pounds her gavel, demanding order in the court. The jurors casually scribble something in their notes, and everybody knows that the fate of the accused has been sealed. But how reliable is a witnesss memory, especially after rehearsing the testimony ad nauseam with a team of lawyers? When a witness presents testimony, is she really remembering the event, or is she remembering something she remembered? Does the initial memory remain intact, or does it degrade like a copy of a copy?

The status of witness testimony in court is just one reason neuroscientists want to understand the biochemical underpinnings of memory formation. Consolidation, the process of new memory formation that takes place in the hippocampus, requires certain proteins. Reconsolidation, the reactivation of these memories in the amygdala, requires a different set of proteins. In the past, neuroscientists hypothesized that reconsolidation might allow old and new memories to link up. A new study by Cristina Alberini and colleagues provides evidence that when rats link new memories to old, the molecular basis of this process actually resembles consolidation.

To manipulate lab rat memories, the researchers used constructions called inhibitory avoidance apparatuses. The first apparatus had two tiny rooms: a well-lit safe room and a pitch-black electric-shock room. Rats spent ten seconds in the first room, the researchers flipped on a light, and the rats entered the shock chamber. Alberini and colleagues knew that the rats had formed a new memory when they hesitated to enter the dark room.

Rats then entered a second apparatus decorated differently from the first apparatus. The safe room smelled of perfume, the walls displayed striped wallpaper, and the floor was made from smooth plastic. For rats in the second apparatus, the researchers flipped on a light but did not let the rats pass into the shock room. Alberini and colleagues deduced that the rats had compiled their memories of both the first and second apparatuses when they hesitated to enter the second dark room during a final test.

The researchers found that rats injected with anisomycin, a drug that inhibits protein synthesis, could not form a new memory of the second apparatus and sometimes forgot the first. This showed that, as predicted, both the formation of new memories and the reconsolidation of old memories require protein synthesis. The researchers demonstrated the distinction between the processes of consolidation and reconsolidation by showing that rats require a certain protein in the hippocampus only for memory consolidation and the same protein in the amygdala only for reconsolidation.

Using a combination of proteins that took advantage of the differences between consolidation and reconsolidation, the researchers inhibited either the rats consolidation mechanism or the reconsolidation mechanism. Then, Alberini and colleagues tested the rats ability to link their memory of the first apparatus to their exposure to the second. Upon repeated trials, the rats with blocked reconsolidation pathways successfully linked memories of both apparatuses, while the rats with blocked consolidation pathways did not. Therefore, the consolidation pathway, and not the reconsolidation pathway, plays a role in memory linkage.

As a cautionary word, the researchers emphasized that their results applied to the fear-based memories created by the electric shock. Future studies may reveal if other types of memory yield the same results.

Snails Helping to Make Viagra for Brain

Sun, 08 May 2005 20:21:38 PST

( from http://www.rxpgnews.com ) Dr Kemenes says: "If you lose your memory, you lose your personality. Impaired long-term memory is a devastating consequence of a variety of diseases affecting millions of people. The knowledge obtained from this work will help us to understand, and ultimately prevent and treat, memory disorders or even enhance normal memory."

He adds: "The aim is to find brain molecules that are crucial for the building up and maintenance of long-term memory and learning. The biggest hope is that we will then be able to find out how to operate those functions and improve the speed at which animals learn, or help them remember for longer periods of time. This would then link into drug development for humans."

To do this, Dr Kemenes and his team, funded by a £750,000 grant from the Medical Research Council, will attempt to chemically enhance or inhibit those functions in the common pond snail.

Snails are ideal for this kind of study because humans and pond snails actually share some important characteristics, unchanged by evolution. These include the basic molecular mechanisms that control long-term memory and learning. These processes involve the activation or suppression of a protein, CREB, which is key to the formation of long-term memory, and found in species ranging from molluscs and flies to rats and man.

These responses can be tested by classic "Pavlovian" experiments that bring about a conditioned response. A snail exposed to the smell of pear drops and then food (sucrose, which they love), for example, will respond weeks later to the smell of pear drops by rhythmically moving its mouth parts in anticipation of food, even when none is provided. This shows that the snail now has a memory associating the smell of pear drops with the arrival of food - a learned and remembered response.

This "flashbulb" memory - created by just one response to stimuli, is complemented in Dr Kemenes' research by another test, where the snail is exposed to a tickling stimulus (which it doesn't like) before food is introduced. It takes much longer for the snail to associate this tickling with the arrival of food. Dr Kemenes will attempt to learn how to inhibit the quickly learned memory and improve the weaker, more slowly-acquired memory at molecular level by using different chemical preparations to activate or suppress the release of the memory-forming CREB protein.

Snails are also vital to this part of Dr Kemenes' research because they have large neurons (nerve cells), which are easily identified, manipulated and observed under a microscope than mammalian brain cells, making them ideal subjects for exploring the learning and memory process at the cellular and molecular level.

"Neural Cliques" Create Real-Time Memories

Tue, 12 Apr 2005 12:52:38 PST

( from http://www.rxpgnews.com ) By simultaneously recording the activity of hundreds of neurons in live mice, researchers have identified clusters of brain cells that act together to form and store memories.

Typically, brain activity is measured in one or a few neurons at a time. But since complex behaviors, like learning and memory, depend on the actions of large sets of neurons, it becomes necessary to determine how these cells work together to allow memories to form.

Joe Tsien and colleagues simultaneously recorded the electrical activity of up to 260 individual neurons of the mouse hippocampus, the brain structure responsible for forming memories of places and events. The researchers recorded this activity in response to three different types of startling conditions.

The authors found that each startling episode produced different brain activity patterns and identified basic coding units in the hippocampus, neural cliques, that respond to the different stimuli. These neural cliques provide a plausible, real-time neural basis of memory formation. Furthermore, activation patterns of neural cliques can generate a set of brain codes that, like the genetic code, seem to be universal across different individuals and species.

Human Eyes learn best in an Uncluttered Setting

Thu, 31 Mar 2005 16:24:38 PST

( from http://www.rxpgnews.com ) If athletes, soldiers and drivers must perform every day in visually messy environments, common sense suggests that any visual training they receive should include distractions and disorder.

New research from the University of Southern California and UC Irvine suggests common sense is wrong in this case.

The human vision system learns best in "clear display" conditions without visual noise, said co-authors Zhong-Lin Lu and Barbara Anne Dosher.

The research has long-range implications for rehabilitation therapy, treatment of individuals with "lazy eye" or related disorders and training of soldiers, police officers and other personnel who must make split-second decisions in chaotic situations.

"Now you can simplify training a lot," said Lu, a professor of psychology in the USC College of Letters, Arts and Sciences. "Soldiers, for example, have to operate with goggles and all kinds of (visual) devices. Pilots have other kinds of goggles, video displays. They operate in different environments with different kinds of noise and different kinds of interference."

"What these results show is, in fact, you only need to train them in a clear display environment."

In their studies, Lu and Dosher asked subjects to identify the orientation of simple geometric patterns flashed on a screen. The subjects' performance improved dramatically after several sessions, in line with other studies that have shown the human eye to be highly trainable.

The difference came in the way subjects adapted to different environments. Those subjects who were trained with clear displays also showed improvement with noisy displays. The reverse was not true: Subjects trained with noisy displays performed no better with clear displays.

"That was a huge surprise to us," Lu said. "High noise training comes for free."

The researchers believe that noisy displays impose an artificial limit on a subject's potential improvement. The roughness of the image trains the eye's "filtering" ability but also masks the internal flaws of the visual system.

In clear display training, by contrast, the eye can focus entirely on reducing the intrinsic noise of human visual processes (the researchers refer to this process as "stimulus enhancement"). In addition, Lu said, clear display training may strengthen image recognition by improving perceptual templates.

The results also suggest that the two types of perceptual learning studied noise filtering and stimulus enhancement take place in different areas of the visual system. By training each eye separately, Lu, USC graduate student Wilson Chu, Dosher and USC undergraduate Sophia Lee found that noise filtering transferred completely from the trained eye to the untrained eye. Stimulus enhancement transferred only partially.

This implies that noise filtering is a "binocular" mechanism that serves both eyes at once, the researchers propose. Stimulus enhancement, on the other hand, is "monocular": The eye that is trained receives most of the benefit.

The researchers concluded that for optimal training, each eye should be trained separately in clear displays.

"Then you're done," Lu said.

Modeling the CaMKII Molecular Memory Switch

Tue, 29 Mar 2005 16:31:38 PST

( from http://www.rxpgnews.com ) Scientists attribute our ability to store apparently infinite numbers of memories for decades to long-lasting changes in the electrical, structural, and biochemical properties of neurons.

One cellular mechanism proposed to be involved in the storage of memorieslong-term potentiationinvolves alterations in the strength of messages passed from one neuron to another across structures known as synapses.

The initiation of long-term potentiation is caused by activation of N-methyl-D-aspartate receptors on the receiving neuron and a subsequent increase in the intracellular calcium concentration in a region of the neuron that is called the postsynaptic density. The increase in calcium, in turn, activates the calcium/calmodulin-dependent protein kinase II (CaMKII). This enzyme seems to play a critical role in long-term potentiation, and has been proposed as one of the leading candidates to act as the molecular switch that maintains stable synapse-specific cellular changes. To fulfill this role, CaMKII would need to have stable UP and DOWN positions, or states, much like a light switch.

Xiao-Jing Wang and colleagues now provide a new analysis that strengthens the argument that CaMKII is a molecular switch involved in the storage of long-term neural changes. The activity of the CaMKII holoenzyme (the complete enzyme consisting of both regulatory and catalytic subunits) is controlled by its autophosphorylation statethe enzyme is able to add phosphate groups to specific amino acids within itself. Previous modeling studies have shown that the interplay between the autocatalytic addition of phosphate groups to CaMKII and the removal of phosphate groups by protein phosphatase-1 (PP1) enzymes produces two stable states of the CaMKII enzyme at basal free calcium levels. The DOWN state is unphosphorylated; the UP state is highly phosphorylated. When there is a transient high input of calcium, as happens when long-term potentiation is induced, the CaMKII enzyme flips from a DOWN state to a persistent UP state.

The questions that Wang and colleagues have now asked are what factors affect the stability of the state of this switch, and how many CaMKII holoenzymes are needed to construct a switch that could last a lifetime. These questions are important because a switch that could be spontaneously reset by small, random fluctuations of the conditions within the postsynaptic density would not be useful in maintaining stable long-term changes. The researchers have used a mathematical probabilistic modeling technique known as Monte Carlo simulation, together with the known biochemical and thermodynamic characteristics of CaMKII and PP1, to test how random fluctuations in the chemical reactions involved in the CaMKII/PP1 system change the state of the switch.

They report that switch state stability requires a balance between the phosphorylation and dephosphorylation rates of CaMKII, and that the turnover rate of the kinasethe replacement of old molecules with new onescritically affects switch stability. However, their main finding is that the lifetime of states of the switch increases exponentially with the number of CaMKII holoenzymes that are present. This finding is important because experimental work by other researchers has estimated that there are about 30 CaMKII holoenzymes present in a typical postsynaptic density, and until Wangs team did their modeling it was unclear whether this number of holoenzymes could build a switch stable enough to last a lifetime. In fact, Wang and co-workers estimate that a switch containing as few as 15 holoenzymes can remain activated for longer than a human lifetime. Thus, the researchers conclude, CaMKII switches may indeed play a critical role in preserving our precious memories throughout our lives.

Mature brain-derived neurotrophic factor is key proteing for long term memory

Thu, 10 Mar 2005 16:42:38 PST

( from http://www.rxpgnews.com ) A cellular enzyme appears to play a crucial role in the manufacture of a protein needed for long-term memory, according to a team of researchers led by scientists at the National Institute of Child Health and Human Development of the National Institutes of Health.

The protein is known as mBDNF, which stands for mature brain-derived neurotrophic factor. In an earlier study, another team of NICHD researchers had shown that mBDNF is essential for the formation of long-term memory, the ability to remember things for longer than a day.

"Understanding how BDNF is made may help us to better understand the learning process, perhaps leading to better treatments for disorders of learning and memory," said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development.

The research team was led by Y.Peng Loh Ph.D, of NICHD's Section on Cellular Neurobiology. The researchers published their work in the January 20 issue of Neuron.

Specifically, the researchers discovered that the enzyme carboxypeptidase E, (CPE) is needed to deliver the early, or inactive, form of BDNFproBDNFto a special compartment in the neuron (nerve cell.) Once in the compartment, proBDNF is chemically converted into active mBDNF. After mBDNF is formed, it is released to the outside of the neuron, where it binds to receptors on other neurons and stimulates them to form long-term memory.

Dr. Loh explained that, like other proteins, proBDNF is made inside the endoplasmic reticulum, a convoluted network of tubes and channels inside the cell. The proBDNF winds through the endoplasmic reticulum until it reaches another structure within the cell, the golgi apparatus. There, the proBDNF binds to CPE, which protrudes from special rafts of fatty, cholesterol-rich molecules known as lipids. If this binding process does not take place, proBDNF cannot be converted to its active form. Dr. Loh explained that the proBDNF molecule has four projections, resembling prongs. These prongs fit into a corresponding indentation on CPE, analogous to the way a plug for an electric appliance fits into an electric wall outlet, Dr. Loh said.

The golgi apparatus then encases the lipid raftsalong with proBDNFin bubble-like structures known as vesicles. Within these vesicles, proBDNF is converted to mBDNF by other enzymes. The vesicles are then transported to the cell's outer membrane, where they remain until they are ready to be secreted. Once the cell receives an electrical signal from another neuron, these vesicles fuse with the cell's outer membrane, open up, and release mBDNF.

During their research, Dr. Loh and her colleagues observed mice genetically incapable of producing CPE. In these mice, proBDNF could not be delivered into the lipid raft-rich vesicles for conversion to mBDNF. Instead, it appeared to leak out of the golgi apparatus, where it leached through the cell membrane without first having been converted to active mBDNF. Because they cannot make mBDNF, CPE-deficient mice have poor long-term memory.

Dr. Loh added that, in the near future, an understanding of the chemical mechanism she and her colleagues deciphered in the current study may provide insight into long-term memory deficits. She explained that other researchers have learned that some human beings lack normal CPE due to mutations in the CPE gene. Future research may determine if the CPE mutation affects these individuals' long-term memory.

Self-reinforcing loop found in Emotional Memory

Wed, 09 Mar 2005 17:42:38 PST

( from http://www.rxpgnews.com ) Researchers exploring the brain structures involved in recalling an emotional memory a year later have found evidence for a self-reinforcing "memory loop" -- in which the brain's emotional center triggers the memory center, which in turn further enhances activity in the emotional center.

The researchers said their findings suggest why people subject to traumatic events may be trapped in a cycle of emotion and recall that aggravates post-traumatic stress disorder (PTSD). They said their findings also suggest why therapies in which people relive such memories and reshape perspective to make it less traumatic can help people cope with such memories.

"This study is the first to really test recall of emotional memories after a long time period," said Cabeza. "Previous studies had only allowed a short time interval, for example minutes, between encoding of the memory and retrieval. Hence, they could not distinguish between the process called consolidation -- in which memories are being established -- and retrieval. Also, they did not distinguish between true recollection of a memory and a vague familiarity. In memory studies, it's very important to distinguish between these two phenomena," he said.

In their study, the researchers showed volunteer subjects images that were pleasant, unpleasant or neutral while their brains were being scanned with functional magnetic resonance imaging (fMRI). In this widely used technique, harmless magnetic fields and radio waves are used to image blood flow in regions of the brain, and increased blood flow is a signature of higher brain activity. The pleasant images were of romantic scenes and sports; the unpleasant images involved injured people and violence, and the neutral pictures depicted buildings or other emotionally non-involving scenes. The subjects were asked to rate the emotional aspects of the images they saw.

Then, a year later, the researchers showed the same subjects a combination of images they had previously seen and new images -- pleasant, unpleasant and neutral -- while their brains were being scanned. They asked the subjects to indicate whether they had seen the images before and whether the memory also brought back associated details. Such details indicated the impact of the picture on the subjects.

The researchers found that the subjects did recall the emotional pictures -- both pleasant and unpleasant -- better than the neutral pictures, and this recall was based on specific recognition of the pictures. This recall was associated with a correlated higher activity in both the amygdala -- the region of the brain responsible for processing emotional memories -- as well as the hippocampus, the main memory-processing center. The study also revealed greater amygdala-hippocampal correlation during recollection of emotional pictures than during recollection of neutral pictures, they said. The researchers said that one way of explaining the "co-activation" of these two centers was that they could be part of a "synergistic mechanism," in which each activates the other during recall of an emotional memory.

Said Dolcos, "One way to interpret our result is that emotion can trigger recollection, and vice versa. The synchronicity between activity in the amygdala and hippocampus could go either way. The emotion enhances recollection, but at the same time by recollecting those events, you would also remember the emotional response. It could be like a loop in which the amygdala interacts with the hippocampus." According to Dolcos, this memory loop could help understand the searing recall of traumatic memories in people with post-traumatic stress disorder.

"In such people, an emotional cue could trigger recall of the event, which would then loop back to a re-experiencing of the emotion of the event," said Dolcos. "Or, remembering the event may trigger the emotional reaction associated with the event, which in turn could trigger more intense recall, in a continuous loop."

Such insights into the nature of emotional memory support a therapeutic process that can affect "reconsolidation" of traumatic memories, said Cabeza. "Some studies have suggested that when you retrieve a memory it can not only be re-encoded, or reconsolidated, but you also put it into a labile state in which it can be transformed. While in such labile state, either the memory itself or the person's perspective of it may be altered." According to Cabeza, therapists working with people suffering from PTSD as a result of the 9/11 terrorist attack have used this technique to alleviate its symptoms.

In further studies, the researchers plan to manipulate the degree of emotion experienced by the subjects, as well as how much detail is remembered, to explore the specific interactions among brain structures in processing emotional memories. They also plan to analyze activity of other regions -- such as those that process spatial, auditory, or visual information -- during emotional memory processing to understand their role. Such studies would yield insights into how emotional memories involve integrating multiple brain regions, they said.

A-Adducin Family of Proteins That Help Build the Cytoskeleton Also Critical in Learning and Memory

Wed, 02 Mar 2005 18:14:38 PST

( from http://www.rxpgnews.com ) A family of proteins that help build the cytoskeleton, or the bones of the cell, also play an important role in learning and memory, according to a study published this month in The Journal of Neuroscience.

Marina Picciotto, associate professor of psychiatry, pharmacology and neurobiology at Yale School of Medicine, and the senior author of the study, studied mice missing one of these proteins--â-adducin--and found the cytoskeleton developed normally. However, the mice were impaired during fear conditioning and memory exercises.

"We were hoping to find a mechanism that cells use to make short term changes in nerve cell communication permanent, but we were surprised that losing â-adducin made such a big change in both the nerve cell communication and in behavioral measures of memory," Picciotto said.

The focus of the study is long-term potentiation, which is a form of neuronal plasticity and may form the biological basis for some kinds of memory. Long-term potentiation refers to the fact that if two neurons in the hippocampus are active at the same time, the connection between them can be strengthened. This change, or potentiation, can last for hours to days. This may serve to lay a foundation for more permanent changes, such as the construction of new connections, or synapses, between the neurons.

"If you learn to do something new, your neurons have to adapt and change to create a stronger, more direct pathway between neurons," Picciotto said. "The protein â-adducin appears to be important for making those new connections."

In this study, the mice that did not have the protein were not able to strengthen a synapse in the hippocampus, which is the area of the brain that enables us to remember people, places and things. "If the mice don't have â-adducin, they can't make a new map," Picciotto said. "It's not enough to just have the electrical properties, the skeleton is very important in making long-lasting changes between nerve cells that result in learning."

Rather than permanent storage, memory is a dynamic, meta-stable process

Sun, 16 Jan 2005 13:30:38 PST

( from http://www.rxpgnews.com ) How do you remember your own name? Is it possible ever to forget it? The memory trace, or engram, "feels" like it is stored permanently in the brain and it will never be forgotten.

Indeed, the current view of memory is that, at the molecular level, new proteins are manufactured, in a process known as translation, and it is these newly synthesized proteins that subsequently stabilize the changes underlying the memory. Thus, every new memory results in a permanent representation in the brain.

But Northwestern University neuroscientist Aryeh Routtenberg has presented a provocative new theory that takes issue with that view. Routtenberg, with doctoral student Jerome L. Rekart, outlined the new theory on memory storage in the January issue of the journal Trends in Neuroscience.

Rather than permanent storage, there is a "dynamic, meta-stable" process, the authors said. Our subjective experience of permanence is a result of the re-duplication of memories across many different brain networks.

For example, one's name is represented in innumerable neural circuits; thus, it is extremely difficult to forget. But each individual component is malleable and transient, and as no particular neural network lasts a lifetime, it is theoretically possible to forget one's own name.

This is seen in the most advanced stages of Alzheimer's disease, the researchers stated.

The advantage of such a precarious storage mechanism is that it is a highly flexible system, enabling rapid retrieval even of infrequent elements, with great advantages over models of permanent storage, said Routtenberg, professor in the department of psychology and in the department of neurobiology and physiology, Judd A. and Marjorie Weinberg College of Arts and Sciences and a leading researcher in the Institute for Neuroscience, Northwestern University.

To achieve this high degree of flexibility, Routtenberg's new theory goes on to propose that the brain stores long-term memory by rapidly changing the shape of proteins already present at those synapses activated by learning.

While it is universally agreed that brain proteins are critical for memory storage, Routtenberg's hypothesis challenges the widely accepted, 40-year-old model that long-term memories are stabilized only once newly synthesized proteins are transported to recently activated synapses.

Indeed, this view is central to the theory of Eric Kandel, who in his Nobel Prize address reinforced the central position of this model in forming long-term memory.

So does memory form because you make more protein, as most neuroscientists believe, or because you change the shape of existing proteins, which are known to be strategically located to effect change within milliseconds of activation?

Part of the answer to this question lies in the fact that there are critical weaknesses in the prevailing view.

"There are enough instances of memory storage in the virtual absence of protein synthesis to compel consideration of alternative models," said Routtenberg.

The authors noted that most of the evidence supporting the current view was obtained by studying the effects of certain drugs, called protein synthesis inhibitors, on memory, leading to the conclusion that synthesis was necessary. The authors outline specific evidence that calls those results into question.

For example, synthesis inhibitors that block the production of new proteins by more than 90 percent often cause no discernible memory impairments. Additionally, protein synthesis inhibitors cause a number of side effects that could lead to memory loss caused by something other than protein synthesis inhibition.

Routtenberg agrees with the view that it is the synapse that is modified in response to learning-associated activity, a position first articulated by Nobelist Ramon y Cajal a century ago. But the difference with the current theory is that he and Rekart do not believe that synaptic modification is brought about by recently synthesized proteins.

Routtenberg's theory, derived from a consideration of extensive, fundamental biochemical information, advocates that learning leads to a post-synthesis (or, post-translational) synaptic protein modification that results in changes to the shape, activity and/or location of existing synaptic proteins. In the Routtenberg-Rekart proposal, this is the only mechanism required for long-term memory.

To maintain some residue of this modification, Routtenberg proposes that the "spontaneous activity" of the brain actually acts to "cryptically rehearse" past events. So, long-term memory storage relies on a positive-feedback rehearsal system that continually updates or fine-tunes post-translational modification of previously modified synaptic proteins. It is in this manner that this model allows for the continual modifications of memories.

In the Routtenberg-Rekart model, post-translational modifications within cells and synaptic dialog and endogenous activity between cells and networks work in concert to perpetuate and update memory representations.

A group of post-translational protein modifications that affect neuronal plasticity present in activated pre-synaptic and post-synaptic elements and regulated by proteases, kinases and phosphatases regulate the efficacy of the synapse in response to a learning event.

These modifications are, in turn, maintained via positive feedback between cells (dialog), which are regulated by synaptic excitation (e.g., via the neurotransmitter glutamate) or inhibition (e.g., via the neurotransmitter GABA).

Thus, the self-sustaining positive feedback system also carries built-in control mechanisms that would prevent runaway feedback leading to the detonation of one massive memory or "thermonuclear" engram.

Although Routtenberg's model may represent a radical departure from the current view of how long-term memories are stored, he believes that scientists need to articulate alternative models other than the prevailing one.

A more accurate description will help address issues of memory loss in mental retardation, aging and Alzheimer's disease. Indeed, new hypotheses can lead to the development of new chemical agents that would successfully target the chemical reactions necessary "We would assert that there is enough substance both in the concerns raised and in the post-translational modification/positive feedback model proposed to energize the search for yet more plausible models of long-term memory storage, and to redirect and reinvigorate the quest to understand the brain substrates of information storage," Routtenberg said.

A restrictive diet in mice reduces the build-up of a substance linked to memory loss.

Wed, 15 Dec 2004 19:09:38 PST

( from http://www.rxpgnews.com ) Restricting the diets of mice reduces the build-up of plaques in the brain that are linked to Alzheimer's disease, according to a USC study.

With obese people generally considered to be at a higher risk for developing Alzheimer's, the research raises questions about whether the findings are potentially applicable to humans.

"This is the first indication that modest changes in the normal diet can slow some aspects of Alzheimer's disease," said Caleb Finch, co-author of the study published in the online version of the journal Neurobiology of Aging.

"But that is far and away yet to be proven for humans. It's a big jump to say that what's true for a mouse in a cage is relevant to people living in our complex world," Finch said.

In the study, conducted with collaborators at the University of South Florida in Tampa, researchers used mice whose DNA had been altered with human genes from two families with early onset hereditary Alzheimer's.

The mice were then split into two groups as young adults: one that could eat all it desired ("ad libitum") and the other that had its food intake reduced by 40 percent over a four-week period (diet- restricted).

The researchers were looking specifically at the formation of plaques caused by a build-up of the fiber-like substance called beta-amyloid.

Made up of proteins and polysaccharides, amyloid plaques are deposited in the brain during Alzheimer's disease. Specifically, plaques accumulate in the hippocampus and frontal cortex of Alzheimer's sufferers - areas responsible for memory.

In the diet-restricted mice, both the amount and size of plaque was about 50 percent less than in mice that ate as much as they wanted.

"The power of this study is that two different sets of [human] family mutations were equally sensitive to the effect of diet and slowing the Alzheimer's-like change," said Finch, holder of the ARCO-William F. Kieschnick Chair in the Neurobiology of Aging at USC.

The next goal is to find out why diet restriction has such profound and rapid effects, Finch said.

"We are going to look into the details of metabolism to try and isolate which of the consequences of diet restriction is at work," Finch said. "Is it the blood glucose? Is it the lowered insulin? Those are two targets."

The other USC researchers on this study were Nilay V. Patel, a former USC postdoc who is now a staff scientist at City of Hope Medical Center, and Todd E. Morgan, a research assistant professor in the Andrus Gerontology Center at USC.

The researchers at the University of Southern Florida are Marcia Gordon, Karen E. Connor, Robert A. Good, Robert W. Engelman, Jerimiah Mason and David G. Morgan.