Findings May Have Important Implications for Treatment of Sleep Disorders and for Understanding Mood and Memory
MENLO PARK, Calif.– July 21, 2008– SRI International announced today that a research team has identified the first example of neurons that are activated in the cerebral cortex during slow wave sleep (SWS). The research, led by Dmitry Gerashchenko and Thomas Kilduff, will be published in the Proceedings of the National Academy of Sciences (PNAS) in a paper titled Identification of a Population of Sleep-Active Cerebral Cortex Neurons. The paper is available via the PNAS Web site starting July 21.
The presence of slow waves in the electroencephalogram (EEG) is the distinctive “signature” of SWS and a type of activity that does not normally occur during wakefulness. For years, researchers have hypothesized that ‘slow-wave activity’ (SWA) is correlated with the recuperative properties of sleep and the brain’s ability to learn, in part, because brain cells are relatively quiet during this time. While populations of neurons activated during sleep have been identified in the forebrain and the hypothalamus, up until this point, neurons in the cortex have been seen as dormant. These new results show that a group of rare neurons are active, rather than at rest, during SWS.
“To date, the role of the cortex in SWA has been a mystery since all cortical cells were thought to be quiescent during SWS,” said SRI’s Dmitry Gerashchenko. “We have discovered that the cortex not only plays a role, but harbors a small population of neurons that is activated during spontaneous and catch-up sleep, which occurs after sleep deprivation.”
The authors found that these neurons are active in the cortex of three species (mice, rats and hamsters) during SWS. “Since these neurons also exist in the human brain, they likely “turn on” while we sleep as well,” said SRI’s Thomas Kilduff, senior director of Neurobiology at SRI in whose laboratory at SRI the work was conducted. Kilduff is also a consulting professor at Stanford University School of Medicine. “As such, these neurons will be important to study in sleep disorders such as insomnia. Activation of these cells during sleep may have important implications for aspects of our behavior and cognitive activities that depend heavily on sleep, such as our daytime performance, memory and mood.”
The research also found that the type of neurons that are "turned on" during sleep are the rarest of all currently known cortical neurons. These cells express the enzyme neuronal nitric oxide synthase (nNOS) and thus make nitric oxide (NO), which regulates blood flow in the brain and periphery.
A notable feature of these results is that the proportion of nNOS neurons that are activated seems to be related to the magnitude of homeostatic sleep drive; that is, the longer animals are kept awake, the more nNOS neurons are activated when the animals finally go to sleep. Additionally, nNOS neurons are the only inhibitory cell type known to have long projections both within and between the two hemispheres of the brain.
“The next step will be to determine whether these neurons are the “superhighway” that conducts slow waves across the cortex during sleep,” Kilduff continued.
The research was conducted by Dmitry Gerashchenko (SRI International), Jonathan P. Wisor (SRI International), Deirdre Burns (SRI International), Rebecca K. Reh (University of Washington), Priyattam J. Shiromani (West Roxbury VA Medical Center and Harvard Medical School), Takeshi Sakurai (Kanazawa University), Horacio O. de la Iglesia (University of Washington), and Thomas S. Kilduff (SRI International and Stanford University School of Medicine).
The research was supported by the National Heart, Lung and Blood Institute, National Institute of Aging, National Institute of Mental Health, and the Sleep Research Society Foundation.
Gerashchenko presented the team’s findings at the SLEEP 2008 symposium, “New Developments in Sleep Research: Molecular Genetics, Gene Expression and Systems Neurobiology" on Monday, June 9. For details on the symposium, visit: http://www.sleepmeeting.org/.
The paper, Identification of a Population of Sleep-Active Cerebral Cortex Neurons, can be found on the PNSA web site, at: http://www.pnas.org/content/105/29/10227.full.pdf+html
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