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

Rapid eye movement (REM) sleep is stress-sensitive and linked to cognitive processes in the prefrontal cortex. Yet, the neuronal mechanisms connecting stress, REM sleep and cortical operations remain unclear. Here, we reveal that prefrontal cortical- and nucleus accumbens-projecting paraventricular thalamic neurons (PVT _NAc ) exhibit sleep-stage dependent activity and modulate cortical REM oscillation in response to stress. We found that PVT _NAc bidirectionally modulate the REM-promoting medullary GABAergic signal, and thus, cortical theta oscillation during REM sleep in an activity-dependent manner, along with the excitation-inhibition balance observed during natural sleep stage transitions. While acute stress enhances REM sleep, repeated stress suppresses it through progressively increased PVT _NAc activation. Notably, acute and chronic stimulation of PVT _NAc recapitulates stress-induced bidirectional changes in REM sleep. Thus, PVT _NAc neurons, by integrating stress and REM signals into forebrain activity, dynamically shape sleep architecture. Persistent elevation in this pathway disrupts REM sleep, thereby providing a mechanism through which stress alters prefrontal cortical processing and, ultimately, cognitive functions.