A thalamic circuit mechanism for stress-dependent modulation of REM sleep

Abstract

Rapid eye movement (REM) sleep, a brain state critical for sleep quality and cortical cognition, is tightly controlled by brainstem circuits and highly sensitive to stress. Yet, how these systems interact to regulate REM sleep and its associated forebrain rhythms remains elusive. Here, we identify a thalamic hub that conveys medullary REM-promoting signals, and integrates stress inputs to regulate REM sleep. A subpopulation of paraventricular thalamic neurons that collaterally project to the cortex and nucleus accumbens (PVT[->]NAc) selectively responds to activation of medulla REM-promoting neurons, and bidirectionally modulates REM-associated theta oscillations in an activity-dependent manner. Their low-frequency activation promotes theta rhythms during REM sleep, while high-frequency activation suppresses them, mirroring the neuronal signatures of acute and chronic stress, respectively. Distinct patterns of PVT[->]NAc neurons underlie the bidirectional stress modulation of REM sleep, partly by differentially engaging prefrontal microcircuits via their collateral projections. Together, our findings uncover a thalamic integrative hub that couples sleep-regulating and stress pathways to adaptively control REM sleep expression.