Neural circuitry of rapid eye movement sleep homeostasis: Mechanistic insights and pathological implications

Abstract

Rapid eye movement (REM) sleep is a unique brain state crucial for emotion, memory, and plasticity. Unlike well-understood non-REM (NREM) sleep homeostasis, REM sleep homeostasis remains less clearly defined. This review highlights recent progress in understanding REM sleep homeostasis, focusing on its neurophysiological markers, neural circuits, and significance for disease development. We start by outlining key theoretical models of REM sleep pressure, rebound, and gating and analyzing electrophysiological markers such as PGO wave density, hippocampal theta oscillations, and the pattern of REM sleep episodes. Then, we explore the hierarchical organization of REM-regulating networks, including brainstem cholinergic-GABAergic loops, hypothalamic centers, and limbic-cortical circuits, that reflect REM sleep pressure and influence its behavioral effects. Importantly, we discuss how disruptions in REM sleep homeostasis may contribute to the pathophysiology of major depressive disorder, post-traumatic stress disorder, and Parkinson's disease through changes in prefrontal-limbic connectivity, monoaminergic signaling, and REM sleep-dependent neuroplasticity. By linking circuit-level mechanisms with clinical implications, this review offers a comprehensive framework for understanding REM sleep homeostasis and guiding new therapies.

Keywords

brainstem nuclei / homeostasis / hypothalamic circuits / limbic system / neuropsychiatric disorders / REM sleep

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