biostudies-literatureTao CNIA NIH HHSNIMH NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)U.S. Department of Health & Human Services | NIH | National Institute of Mental HealthU.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication DisordersU.S. Department of Health & Human Services | NIH | National Eye InstituteNEI NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeNIDCD NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)NINDS NIH HHSU.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)8575https://www.ebi.ac.uk/biostudies/studies/S-EPMC11452203biostudies-literatureUnknown15(1)Dysregulation of brain homeostasis is associated with neuropsychiatric conditions such as major depressive disorder. However, underlying neural-circuit mechanisms remain not well-understood. We show in mice that chronic restraint stress (CRS) and social defeat stress (SDS) are both associated with disruption of excitation (E)-inhibition (I) balance, with increased E/I ratios, in medial preoptic area (MPOA) circuits, but through affecting different neuronal types. CRS results in elevated activity in glutamatergic neurons, and their suppression mitigates CRS-induced depressive-like behaviors. Paraventricular hypothalamic input to these neurons contributes to induction but not expression of depressive-like behaviors. Their projections to ventral tegmental area and periaqueductal gray/dorsal rNature communicationsExcitation-inhibition imbalance in medial preoptic area circuits underlies chronic stress-induced depression-like states.PMC11452203EY019049MH116990U01 MH116990RF1 NS132912R01 DC020887R01 DC008983R01DC008983RF1NS132912R01 EY019049R01 AG089756Zhang GWSun WJHuang JJZhang LITao CTao HWfalseExcitation-inhibition imbalance in medial preoptic area circuits underlies chronic stress-induced depression-like states.Dysregulation of brain homeostasis is associated with neuropsychiatric conditions such as major depressive disorder. However, underlying neural-circuit mechanisms remain not well-understood. We show in mice that chronic restraint stress (CRS) and social defeat stress (SDS) are both associated with disruption of excitation (E)-inhibition (I) balance, with increased E/I ratios, in medial preoptic area (MPOA) circuits, but through affecting different neuronal types. CRS results in elevated activity in glutamatergic neurons, and their suppression mitigates CRS-induced depressive-like behaviors. Paraventricular hypothalamic input to these neurons contributes to induction but not expression of depressive-like behaviors. Their projections to ventral tegmental area and periaqueductal gray/dorsal r2024-01-01T00:00:00Z2024 Oct2026-06-09T07:20:36.827Z2025-04-06T22:33:56.004ZS-EPMC114522033936286010.1038/s41467-024-52727-2