A Motor Theory of Sleep-Wake Control: Arousal-Action Circuit

Abstract

Wakefulness, rapid eye movement (REM) sleep, and non–rapid eye movement (NREM) sleep are characterized by distinct electroencephalogram (EEG), electromyogram (EMG), and autonomic profiles. The circuit mechanism coordinating these changes during sleep-wake transitions remains poorly understood. The past few years have witnessed rapid progress in the identification of REM and NREM sleep neurons, which constitute highly distributed networks spanning the forebrain, midbrain, and hindbrain. Here we propose an arousal-action circuit for sleep-wake control in which wakefulness is supported by separate arousal and action neurons, while REM and NREM sleep neurons are part of the central somatic and autonomic motor circuits. This model is well supported by the currently known sleep and wake neurons. It can also account for the EEG, EMG, and autonomic profiles of wake, REM, and NREM states and several key features of their transitions. The intimate association between the sleep and autonomic/somatic motor control circuits suggests that a primary function of sleep is to suppress motor activity.

A role for the cortex in sleep-wake regulation

“…In summary, our study suggests an important role for the cortex not only in the dynamics of local network oscillations, but also in sleep homeostasis and the global control of sleep-wake states. This finding supports the idea that brain structures fundamentally involved in sleep regulation extend far beyond the traditionally considered subcortical circuitry 4,12,34 .…”

“…Early studies based on neurological case reports, transections and electrical stimulation suggested that global state transitions are mediated via a distributed circuitry across the brainstem, the hypothalamus and the basal forebrain 1,2 . Recent studies using selective targeting of subcortical neuronal populations based on their gene expression or connectivity patterns, have highlighted a growing complexity within the sleep-wake promoting circuitry, with distinct neuronal subtypes responsible for specific aspects of wakefulness and sleep 3,4 .…”

The role of the hypothalamus in cortical arousal and sleep homeostasis

“…This model was able to account for rapid and complete transitions between sleep and wakefulness, and for preventing state instability (Mochizuki et al, 2004) or an occurrence of mixed, hybrid states of vigilance (Mahowald et al, 2011). However, over the last decade, our knowledge of subcortical brain nuclei that control sleep has expanded steadily, leading to the identification of functional specialization within the sleep-control network, and in parallel, highlighting a previously underappreciated complexity (Chung et al, 2017;Herrera et al, 2016;Kroeger et al, 2018;Liu and Dan, 2019;Liu et al, 2020;Ma et al, 2019;Oishi et al, 2017;Weber et al, 2018;Zhang et al, 2015;Zhong et al, 2019).…”

Dopamine-gated memory selection during slow wave sleep

“…As well as prospectively prioritising, or tagging, memories for later replay during sleep, dopamine may directly act during sleep per se (18). As engram storage evolves, newly acquired memories are spontaneously repeated (17); sleep affords an optimal neurophysiological state during which to enact this process -although replay occurs during wake too (19).…”