Regulation of striatal dopamine release by PLCγ1 in dopamine neurons: Involvement of VMAT2 and Synapsin III

Abstract

Dopamine neurons play a pivotal role in voluntary movement, reward learning, and motivation, whose dysfunction is closely related to various psychological and neurodegenerative diseases. Therefore, comprehending the detailed signaling mechanisms that functionally regulate dopamine neurons is indispensable for the development of more effective therapeutic strategies against dopamine-related disorders. In this study, we investigate the physiological role of phospholipase Cγ1 (PLCγ1), one of the key effector enzymes involved in intracellular signaling, on regulating dopaminergic function in vivo. Our findings indicate that cell type-specific deletion of PLCγ1 does not adversely affect the morphology and structure of midbrain dopamine neurons. However, it does facilitate dopamine release from dopaminergic axon terminals in the striatum. Elevated dopamine release was accompanied by increased vesicular monoamine transporter 2 (VMAT2) co-localization at dopaminergic axons. Notably, dopamine neuron-specific knockout of PLCγ1 also leads to the heightened expression and co-localization of synapsin III, a protein involved in the regulation of synaptic vesicle trafficking. Our findings suggest that PLCγ1 in dopamine neurons could play a crucial role in modulating dopamine release at axon terminals by directly or indirectly interacting with synaptic machinery, including VMAT2 and synapsin III.