EFFECTS OF STRESS ON SLEEP: ROLE OF CRH-EXPRESSING NEURONS IN THE VLPO

Stress disturbs sleep through neuronal mechanisms that remain poorly understood. We previously showed that activation of the monosynaptic pathway between the prefrontal cortex (PFC) and the ventrolateral preoptic area (VLPO) shortens rapid eye movement (REM) sleep episodes after social defeat stress in mice. We show that VLPO neurons expressing corticoliberin (CRH) receive excitatory inputs from the PFC. This study aims to clarify the role of VLPO CRH neurons in post-stress sleep regulation. We combined chemogenetic manipulations of VLPO‑CRH neurons with corticosterone assays and fiber photometry to relate their activity to sleep architecture and the systemic stress response. Social defeat elevates corticosterone levels, induces an initial insomnia and is followed by a marked reduction in REM sleep. Chemogenetic activation of VLPO-CRH neurons in control conditions alters REM sleep, notably by decreasing theta oscillation frequency. Chemogenetic inhibition has no effect at baseline conditions, but after social defeat, prevents the stress-induced REM sleep inhibition immediately after insomnia. Ongoing fiber photometry recordings will determine how VLPO‑CRH calcium dynamics relate to vigilance state transitions and to the time course of stress‑induced REM sleep changes. We also aim to test the potentially restorative role of post-stress REM sleep by measuring corticosterone after sleep, comparing a normal post-stress condition with a condition in which chemogenetic inhibition of VLPO-CRH neurons prevents REM sleep suppression. VLPO-CRH neurons thus emerge as a critical link between stress and REM sleep regulation, mediating stress-induced REM sleep suppression, while their inhibition abolishes this effect and normalizes REM sleep after stress.