Sleep Disorders
Mushroom bodies regulate sleep like a snooze button
Jun 8, 2006 - 5:36:37 AM

With help from some drowsy fruit flies, a team of researchers from the Howard Hughes Medical Institute (HHMI) at the University of Pennsylvania School of Medicine has identified a region of the fruit fly's brain that is crucial to controlling sleep.

The finding, reported in the June 8, 2006, issue of the journal Nature, is important because it identifies a new role for brain structures, called mushroom bodies, which have now been shown to control fruit fly slumber. Mushroom bodies were known to be involved in processing sensory information and memory. Thus, the new studies lend support to the idea that sleep helps the brain consolidate learning and memory.

“We spend one-third of our lives sleeping, but we know very little about sleep and how it is regulated,” explained Amita Sehgal, the senior author of the new Nature paper and an HHMI investigator at the University of Pennsylvania School of Medicine. “The research actually doesn't tell us much directly about the purpose of sleep,” said Sehgal. “But one of the things suggested (from past research) is that sleep helps consolidate memory.”

Consequently, the finding by Sehgal and her colleagues showing that sleep and memory share a common locus in the brain may begin to substantiate why our brains must routinely descend into the idling metabolic and electrical state that defines sleep.

Sehgal's group conducted a series of experiments with sleeping flies that fingered mushroom bodies as at least one of the brain's primary snooze buttons.

“Mushroom bodies are an anatomical structure in the fly brain, mostly associated with learning and memory,” said Sehgal, who conducted the research at Penn's Center for Sleep and Respiratory Neurobiology. “They also process olfactory cues and locomotor activity.”

It is possible, Sehgal and her colleagues speculate, that the mushroom bodies constitute a gate to fly dreamland: sleep occurs when the stream of sensory information processed by the structure — an elaborate net of neural cells — is inhibited.

In humans and other higher animals, sleep has been associated with several different structures in the brain, mostly by looking at brain waves, the patterns of electrical signals generated during sleep or wakefulness. There are no structures analogous to mushroom bodies in vertebrates, but the hippocampus and/or thalamus may harbor a similar control center for human sleep, Sehgal noted.

“In the fly, the mushroom bodies are probably not the only thing associated with sleep.”

“Once you have (linked sleep to an anatomical structure), you can figure out changes taking place at the molecular level in that region of the brain,” Sehgal explained. “It allows us to shift our efforts to see what happens during sleep and what happens when we're awake that leads to sleep.”

The HHMI team was able to home in on mushroom bodies' role in regulating sleep in flies by using the drug RU-486 in their studies. “RU-486 is a steroid that acts on steroid-regulated promoters,” she explained. “We used RU-484-responsive sequences to control our gene of interest and once we had done that in the fly, we could feed the fly RU-486 to turn that gene on.”

Sehgal and her team were then able to induce large changes in sleep by using RU-486 to manipulate a critical gene known as protein kinase (PKA), which makes a protein that, in the brain, activates other proteins and switches other genes on or off.

In flies, the duration of sleep is inversely related to PKA activity. By expressing the gene in different regions of the brain, including mushroom bodies, it was possible to assess the roles of those structures in the phenomenon of sleep.

Sehgal said that a fly is sleeping if it remains motionless for extended periods. “At the moment, our definition of fly sleep is five minutes of immobility,” she explained. In addition to identifying the structure that governs sleep in invertebrates, the new HHMI work promises to help researchers zero in on the anatomical structures in the brains of higher animals, including humans, which govern sleep.

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