The deletion of PLCγ1 leads to the dysfunction of dopaminergic neuron

Abstract

Dopamine is one of the key neuromodulators critical for motor function, reward, motivation, and addiction. Malfunction of this dopamine and dopaminergic neuron is associated with various psychological and neurodegenerative diseases. Most of the previous studies investigating dopamine-related brain disorders have focused on the postsynaptic functions of dopamine such as dopamine receptor signaling. However, the key intracellular signaling pathway regulating the physiological function is still not fully understood in dopamine neurons. Phospholipase Cγ1 (PLCγ1), mainly activated by receptor tyrosine kinase (RTK), regulates diverse neuronal functions in the brain through the activation of protein kinase C and intracellular calcium release. Several studies suggest 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 deletion of PLCγ1 in dopaminergic neurons resulted in the cellular alterations, decreased the number of dendritic spine, and altered synaptic transmission. In addition, the dysfunction of dopaminergic neurons changed the dopamine-related behaviors. This study will provide the fundamental understanding of intracellular signaling pathway critical for dopaminergic neurons.