The How and Why of Sleep: Motor Theory and Catecholamine Hypothesis

The transition from wakefulness to sleep is associated with profound changes in the brain and body. In addition to altered states of consciousness, there are marked reductions in somatic and autonomic motor activity. To understand how mammalian sleep is generated, whole-brain screening for sleep neurons has revealed a large network spanning the forebrain, midbrain, and hindbrain. We unify various experimental findings in a “motor theory”, in which the sleep-control mechanism is integral to somatic and autonomic motor control circuits, allowing coordinated reductions in mental arousal and physical activity for sleep generation. Regarding the why question, sleep deprivation is known to cause metabolic and immune disruptions in addition to cognitive and emotional impairments, but could these diverse effects be traced to a single, basic biological process? We here propose a “catecholamine hypothesis”, in which inactivation of catecholamine (dopamine, noradrenaline and adrenaline) signaling is essential for not only sleep generation but also the various benefits of sleep. Besides promoting brain arousal and somatic/autonomic motor activity, catecholamines are master regulators of metabolic and immune functions; suppression of catecholamine activity during sleep has wide-ranging effects that together facilitate repair and rejuvenation. Furthermore, catecholaminergic neurons are particularly vulnerable to metabolic stress and neurodegeneration. Such vulnerability, hence the recurring need for rest and recovery of these neurons, may be a major cause for homeostatic sleep pressure. Thus, the motor theory offers a simple framework for understanding how sleep is controlled by a distributed circuit mechanism, and the catecholamine hypothesis posits a singular process that underpins the multifaceted reasons for sleep.