What Is the Role of the Locus Coeruleus in Sleep, Cerebrovascular Control, and Glymphatic Clearance?

The locus coeruleus (LC) has a major role in mechanisms of arousal, attention, and emotional responses. Increasing evidence indicates that the LC also regulates sleep architecture and triggers phasic autonomic and hemodynamic events during non-rapid eye movement (NREM) sleep. Ultraslow oscillations of LC activity reduce spindle density during N2 and are phase locked to slow waves during N3, whereas LC silencing promotes the NREM-REM sleep transition. The LC also regulates the function of the neurovascular unit and promotes functional hyperemia. Recent studies show that oscillations of LC neuronal activity induce tightly synchronized cycles of vasoconstriction and vasodilation that function as a pump that propels CSF along periarterial space, thereby driving metabolite clearance via the glymphatic system. Glymphatic clearance is a fundamental mechanism for maintaining brain health and homeostasis, with broad implications for the development of preventive and therapeutic strategies in neurologic diseases.