Novel mechanism of sleep-wake control.
PI/Investigator: Nebojsa Kezunovic, graduate student; E. Garcia-Rill, COBRE PI.
Institution: Center for Translational Neuroscience (COBRE), Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR
Background: When we are awake with our eyes closed, electrodes on the scalp measure waves of human brain activity at 10 Hertz, or 10 per second. If we fall asleep, these waves slow to 6-8 Hertz during drowsiness and light sleep, and then to 2-4 Hertz in deep sleep. When we open our eyes, are alerted and pay attention, our brains begin to fire at 20-40 Hertz. These waves are called “gamma band activity”, and are present during consciousness and learning, and also during dreaming. Dogma was that “gamma band activity” was only present in the cerebral cortex. Recently, investigators found “gamma band activity” in other parts of the brain, such as the hippocampus and cerebellum.
Advance: Studies at the Center for Translational Neuroscience at UAMS have discovered that parts of the reticular activating system (RAS), the part of the brain that controls sleep, dreaming and waking, exhibit “gamma band activity”. In fact, nerve cells in this area prefer to fire at ~40 Hertz when stimulated. This means that the RAS activates the rest of the brain when we are alerted, and it does so, not by triggering such activity in other regions, but by itself inducing “gamma band activity”. This process thus recruits waking or dreaming. We identified the mechanism of action as the presence of voltage-dependent calcium channels (P/Q-type) that lead to these rapid oscillations.
Support: Core Facilities provided by COBRE award P20 GM104325.
Public Health Impact: This novel mechanism suggests that the RAS is more about “waking” than it is about “sleep”. Now that we know that these channels mediate high frequency oscillations, the development of new anesthetics (to block these channels) and stimulants (to activate these channels) is not far behind.
Citation and links:
Kezunovic, N., Urbano, F.J., Simon, C., Hyde, J., Smith, K., and Garcia-Rill, E. Mechanism behind gamma band activity in the pedunculopontine nucleus (PPN). Eur J Neurosci 34: 404-415, 2011. PMID: 21722210, PMCID requested.