Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice

Détails

ID Serval
serval:BIB_6FE9374F8C21
Type
Autre: (aucun autre type ne convient)
Collection
Publications
Institution
Titre
Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice
Auteur(s)
Petrelli Francesco, Zehnder Tamara, Pucci Luca, Cali Corrado, Bondiolotti Bianca Maria, Perez Alicia Molinero, Dallerac Glenn, Déglon Nicole, Giros Bruno, Magara Fulvio, Magrassi Lorenzo, Mothet Jean-Pierre, Simmler Linda, Bezzi Paola
Date de publication
27/01/2021
Langue
anglais
Résumé
Astrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).
Open Access
Oui
Création de la notice
13/09/2021 11:51
Dernière modification de la notice
14/09/2021 5:41
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