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.