Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice
Details
Serval ID
serval:BIB_6FE9374F8C21
Type
Autre: use this type when nothing else fits.
Collection
Publications
Institution
Title
Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice
Issued date
27/01/2021
Language
english
Abstract
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
Yes
Create date
13/09/2021 11:51
Last modification date
14/09/2021 5:41