Dopaminergic Control of Glial Cells in Prefrontal Cortex Functions

Project Summary Recent research in the study of brain functions is highlighting the important role of glial cells in several human neurological and psychiatric disorders. The dopaminergic control of brain functions is classically assigned to the effect of dopamine on neurons. However, D2R expression has also been reported in astrocytes, questioning what their contribution in the dopamine-dependent control of brain functions is. Based on preliminary evidence showing an increase of astrocytes and microglia in the PFC of mice with an altered control over dopamine synthesis and release, we hypothesize that D2R signaling in astrocytes influences the activity of neighboring cells and induces microglia proliferation. This mechanism could play a role in the control of PFC dependent behavior, gene expression in astrocytes and microglia, as well as on the metabolites that they produce. Thus, we propose to perform experiments to determine the impact of D2R signaling in astrocyte on PFC functions. We will use viral vectors to knockdown D2R specifically in astrocytes in mice with either a normal control of dopamine synthesis and release or in mutants where these functions have been altered. This project is timely due to the increased involvement of glia in brain disorders and promises to elucidate mechanisms previously unexplored.