Title: Shapping the mind with glia: new role of glial VMAT2 in dopamine homeostasis and cerebral functions

Speaker: Jean-Pierre Mothet, PhD

Abstract:

Dopamine signaling supports higher-order cognitive functions and is dysregulated in many neuropsychiatric disorders, including schizophrenia and autism. However how the dopaminergic tone is controlled remains, to date, elusive. Here, I will present compelling evidence showing that astrocytes are engaged in the homeostasis of brain monoamines. Indeed, we show that a subset of astrocytes during postnatal development of frontal and prefrontal cortex are endowed with unique features of “dopaminergic glial cells” insofar as they control dopamine homeostasis by expressing some of the core proteins for dopamine uptake, storage and metabolism. Conditional gene inactivation of the vesicular monoamines type 2 transporter (VMAT2) in astrocytes postnatally produces aberrant dopamine metabolism and reduced extracellular levels of dopamine, increased synaptic transmission and density of mature spines as well as defects in synaptic plasticity. Consequently, mutant mice devoid of astroglial VMAT2 develop decreased executive functions, increased anxiety and compulsive-like repetitive behaviours as well as social defects. Our findings show that alteration of the homeostatic control of dopamine by astrocytes produces alterations of network activity and behaviour frequently observed in neurodevelopmental disorders.

Host: Prof. Yi Rao

20170221