Genetic deletion of PLCγ1 leads to the dysfunction of dopamine neurons

Abstract

Dopamine, one of the essential neuromodulators, plays important roles in voluntary movement, reward, and motivation. In addition, both malfunction and degeneration of dopaminergic neurons are related to various psychological and neurodegenerative diseases such as ADHD, addiction, schizophrenia, and Parkinson's disease. Therefore, understanding the detailed signaling mechanisms maintaining dopaminergic neurons under normal and pathological conditions is crucial for the development of better therapeutic strategies against dopamine-related disorders. Phospholipase Cγ1 (PLCγ1) is a key enzyme in the intracellular signaling that regulates diverse neuronal functions in the brain through the activation of protein kinase C and intracellular calcium release. Previous studies have proposed that PLCγ1 is implicated in the development and function of dopaminergic neurons, while the specific molecular mechanisms remain to be determined. In this study, we focused on the dopaminergic neuron-specific regulatory function of PLCγ1 in vivo. We found that the genetic deletion of PLCγ1 in dopaminergic neurons resulted in cellular alterations, decreased the number of dendritic spines, and altered synaptic transmission. Furthermore, the dysfunction of dopaminergic neurons changed dopamine-related behaviors. Our findings will provide the fundamental understanding of intracellular signaling pathway critical for dopaminergic neurons.