Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice
| Autor: | Bianca Maria Bondiolotti, P. Bezzi, Nicole Déglon, Alicia Molinero Perez, Luca Pucci, Corrado Calì, Francesco Petrelli, Jean-Pierre Mothet, Tamara Zehnder, Glenn Dallérac, Lorenzo Magrassi, Bruno Giros, Fulvio Magara, Linda D. Simmler |
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| Přispěvatelé: | Université de Lausanne = University of Lausanne (UNIL), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), McGill University = Université McGill [Montréal, Canada], Università degli Studi di Pavia = University of Pavia (UNIPV), Laboratoire Lumière, Matière et Interfaces (LuMIn), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Université de Genève = University of Geneva (UNIGE), University of Rome la Sapienza, Departement of internal medicine and laboratory of gene expression, Dallérac, Glenn, Lausanne University Hospital, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), University of Lausanne (UNIL), Università degli Studi di Pavia, University of Geneva [Switzerland] |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
[SDV]Life Sciences [q-bio] [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Striatum AMPA receptor Biology Vesicular monoamine transporter 2 Phenotype behavioral disciplines and activities [SDV] Life Sciences [q-bio] 03 medical and health sciences 0302 clinical medicine nervous system Dopamine Obsessive compulsive medicine biology.protein NMDA receptor Prefrontal cortex Neuroscience 030217 neurology & neurosurgery psychological phenomena and processes 030304 developmental biology medicine.drug |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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