Basal forebrain regulation of sleep-wake state.

Sleep and wake are fundamental biological processes present in virtually all species of animals. Yet we still do not fully understand what mechanisms regulate sleep/wake states. To address this question, we focus our research on the part of the brain called the basal forebrain. The basal forebrain is known for its critical role in activating the cortex, the part of the brain responsible for "higher" brain functions such as perception and planning. Recently, we showed that the basal forebrain also plays an important role in promoting sleep after sleep loss; damage to this region in rodents can impair their ability to compensate for lost sleep. The execution of these functions by the basal forebrain requires appropriate and timely inputs from the rest of the sleep/wake system, and the basal forebrain's ability to monitor and signal sleep need to specific targets. In the proposed research, we will investigate how various types of inputs from the rest of the sleep/wake system modulate the activity of specific basal forebrain cells to induce behavioural and cortical activation. We will also examine how these multiple signals interact and whether there are functional changes in the inputs after sleep deprivation. Finally, we will investigate how basal forebrain cells monitor sleep need and signal to the rest of the brain to initiate compensatory sleep. Towards these goals, we will use polygraphic sleep-wake state recording, infusion of wake-promoting transmitters, a selective neurotoxin, and cellular recordings from brain slices. Understanding sleep-wake regulation can have significant health and economic impact, as inadequate sleep is becoming more common in our society. It is our hope that the research proposed here will ultimately help in the development of better strategies for improving the quality of sleep and for coping with the negative impact of inadequate sleep.