REM Sleep Regulating Mechanisms in the Cholinergic Cell Compartment of the Brainstem

Rapid eye movement (REM) sleep is a highly evolved yet paradoxical behavioral state (highly activated brain in a paralyzed body) in mammalian species. Since the discovery of REM sleep and its physiological distinction from other sleep states¹, a vast number of studies in neurosciences have been dedicated toward understanding the mechanisms and functions of this behavioral state. Collectively, studies have shown that each of the physiological events that characterize the behavioral state of REM sleep is executed by distinct cell groups located in the brainstem. These cell groups are discrete components of a widely distributed network, rather than a single REM sleep center. The final activity within each of these executive cell groups is controlled by the ratio of cholinergic neurotransmission emanating from the pedunculopontine tegmentum (PPT) to aminergic neurotransmission emanating from the locus coeruleus (LC) and raphe nucleus (RN). In this review, we summarize the most recent findings on the cellular and molecular mechanisms in the PPT cholinergic cell compartment that underlie the regulation of REM sleep. This up-to-date review should allow clinicians and researchers to better understand the effects of drugs and neurologic disease on REM sleep.