An overview of sleep–wake circuitry

How and when we wake and sleep are under the control of incredibly complex neural circuitry, consisting of neuronal populations (or nodes), neurotransmitters, and pathways that form orchestrated wake- or sleep-promoting networks. When any aspect of this neural circuitry is impaired (e.g. disease) or altered by external factors (e.g. stress), sleep and wake can be disrupted, sometimes quite profoundly. As one example, selective loss of orexin neurons in the lateral hypothalamus results in the sleep disorder narcolepsy. While our understanding of how discrete circuit elements in the brain work together to regulate wake and sleep remains incomplete, the relatively recent development of genetically driven tools and techniques has enabled a far more detailed understanding of the functional and structural basis of this circuitry. In this chapter, we review the current state of our understanding of the brain circuitry regulating sleep and wake, including how disruption of discrete circuit elements underlies a myriad of sleep- and wake-disorders.