Skip to Main content Skip to Navigation
Journal articles

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 replicated by pairing activation of LDTg cholinergic terminals in the VTA with a moderate stress. Prevention of CSD outcomes are recapitulated by blocking corticotropin-releasing factor receptor 1 within the LDTg. These data uncover a neuro-circuitry of depressive-like disorders and demonstrate that stress, via a neuroendocrine signal, profoundly dysregulates the LDTg.
Document type :
Journal articles
Complete list of metadatas

Cited literature [58 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-01907538
Contributor : Gestionnaire Hal-Su <>
Submitted on : Monday, October 29, 2018 - 11:21:18 AM
Last modification on : Tuesday, December 8, 2020 - 3:33:49 AM
Long-term archiving on: : Wednesday, January 30, 2019 - 2:21:32 PM

File

s41467-018-06809-7.pdf
Publication funded by an institution

Identifiers

Citation

Sebastian Fernandez, Loïc Broussot, Fabio Marti, Thomas Contesse, Xavier Mouska, et al.. Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors. Nature Communications, Nature Publishing Group, 2018, 9, pp.4449. ⟨10.1038/s41467-018-06809-7⟩. ⟨hal-01907538⟩

Share

Metrics

Record views

215

Files downloads

305