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

0 avis

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

Archive ouverte

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

Langue: en

Consulter en ligne

Consulter le document

Suggestions

Du même auteur

Dopamine and glutamate receptors control social stress-induced striatal ERK1/2 activation

Archive ouverte | Contesse, Thomas | CCSD

International audience. Stress has been acknowledged as one of the main risk factors for the onset of psychiatric disorders. Social stress is the most common type of stressor encountered in our daily lives. Uncoveri...

A non-canonical GABAergic pathway to the VTA promotes unconditioned freezing

Archive ouverte | Broussot, Loïc | CCSD

International audience. Freezing is a conserved defensive behaviour that constitutes a major stress-coping mechanism. Decades of research have demonstrated a role of the amygdala, periaqueductal grey and hypothalamu...

Nicotinic receptors promote susceptibility to social stress in female mice linked with neuroadaptations within VTA dopamine neurons

Archive ouverte | Ortiz, Vanesa | CCSD

International audience. Abstract There are about twice as many women as men who experience depression during their lifetime. Although life circumstances and especially exposure to stressful situations constitute a m...

Chargement des enrichissements...