Ventral tegmental area GABA neurons mediate stress-induced anhedonia
Ventral tegmental area GABA neurons mediate stress-induced anhedonia
Abstract Stressful experiences frequently precede depressive episodes1. Depression results in anhedonia, or disrupted reward-seeking, in most patients2. In humans3,4 and rodents5,6, stress can disrupt reward-seeking, providing a potential mechanism by which stress can precipitate depression7-9. Yet despite decades investigating how stress modulates dopamine neuron transmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc), the underpinnings of the stress-anhedonia transition remain elusive10-13. Here we show that during restraint stress, VTA GABA neurons drive low frequency NAc LFP oscillations, rhythmically modulating NAc firing rates. The strength of these stress-induced NAc oscillations predict the degree of impaired reward-seeking upon release from restraint. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and reverses the effect of stress on reward-seeking. By contrast, mimicking these oscillations with rhythmic VTA GABA stimulation in the absence of stress blunts subsequent reward-seeking. These experiments demonstrate that VTA GABA inputs to the NAc are both necessary and sufficient for stress-induced decreases in reward seeking behavior, elucidating a key circuit-level mechanism underlying stress-induced anhedonia.
Lowes Daniel C.、Chamberlin Linda A.、Firdous Ayesha、Park Alan J.、Holt Emma S.、Abbas Atheir I.、Gordon Joshua A.、Kretsge Lisa N.、Harris Alexander Z.、Bretton Zachary H.、Yusufova Lyubov
Department of Psychiatry, Columbia University, College of Physicians and SurgeonsDepartment of Psychiatry, Columbia University, College of Physicians and SurgeonsDepartment of Psychiatry, Columbia University, College of Physicians and SurgeonsDepartment of Psychiatry, Columbia University, College of Physicians and Surgeons||Division of Systems Neuroscience, New York State Psychiatric Institute||The Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia UniversityDepartment of Psychiatry, Columbia University, College of Physicians and SurgeonsVA Portland Health Care System, Department of Behavioral Neuroscience and Department of Psychiatry, Oregon Health & Science UniversityNational Institute of Mental HealthDepartment of Psychiatry, Columbia University, College of Physicians and SurgeonsDepartment of Psychiatry, Columbia University, College of Physicians and Surgeons||Division of Systems Neuroscience, New York State Psychiatric InstituteDepartment of Psychiatry, Columbia University, College of Physicians and SurgeonsDepartment of Psychiatry, Columbia University, College of Physicians and Surgeons
神经病学、精神病学基础医学生理学
Lowes Daniel C.,Chamberlin Linda A.,Firdous Ayesha,Park Alan J.,Holt Emma S.,Abbas Atheir I.,Gordon Joshua A.,Kretsge Lisa N.,Harris Alexander Z.,Bretton Zachary H.,Yusufova Lyubov.Ventral tegmental area GABA neurons mediate stress-induced anhedonia[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2020.05.28.121905.点此复制
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