Grant: Operating Grant

The sleep-waking cycle in mammals is comprised of three distinct states: waking (W), slow wave sleep (SWS) and rapid eye movement sleep (REMS) or paradoxical sleep (PS). These states are generated by neuronal systems distributed through the core of the brain and by the chemicals utilized by these neurons as neurotransmitters. To understand how these neurons generate sleep-wake states, we must learn how they discharge and thus release their chemicals across the sleep-waking cycle. With this aim (1) and by applying optogenetics in mice, we propose to record while manipulating during natural sleep-wake states and labeling for subsequent histochemical identification, neurons which utilize acetylcholine (ACh), GABA or glutamate as neurotransmitters. We can thus distinguish and study how specific neurons promote cortical activation or behavioral arousal of wakefulness versus those which dampen cortical activation or behavioral arousal. The sleep-waking cycle is also regulated in a homeostatic manner such that an imbalance created by deprivation of sleep will be compensated for by a subsequent increase in sleep. Understanding how this homeostatic regulation occurs necessitates learning how the responsiveness of specific neuronal groups to the neurotransmitters released might be altered following sleep deprivation and recovery. With this aim (2), we propose to examine using histochemical staining following sleep deprivation versus sleep recovery, levels of receptors for excitatory (glutamate) and inhibitory (GABA) neurotransmitters, along with levels of regulatory proteins. We can thus determine how homeostatic scaling of excitability in specific neuronal groups can promote recovery of sleep. Collectively, these studies will illuminate the way in which normal sleeping and waking are generated and regulated and how disorders like narcolepsy and insomnia can result from neural-chemical imbalances in these systems.