Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors.

ABSTRACT: Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals remain largely unknown. We demonstrate that chronic social defeat (CSD) stress, a preclinical paradigm of depression, causes marked hyperactivity of laterodorsal tegmentum (LDTg) excitatory neurons that project to the VTA. Selective chemogenetic-mediated inhibition of cholinergic LDTg neurons prevent CSD-induced VTA DA neurons dysregulation and depressive-like behaviors. Pro-depressant outcomes are replicate

SUBMITTER: Fernandez SP 

PROVIDER: S-EPMC6202358 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature