Fine-tuning of dopaminergic synapse by microglial engulfment

Abstract

Microglia actively regulate neuronal and synaptic functions through synaptic engulfment, a process well characterized at excitatory and inhibitory synapses. However, its role at modulatory synapses, including dopaminergic synapses, remains poorly understood. Here, we demonstrate that dopaminergic presynaptic boutons in the mouse striatum are selectively engulfed by microglia under diverse physiological and pathological conditions. Notably, chemogenetic modulation of neuronal activity via DREADD GPCR activation dynamically alters microglial engulfment of dopaminergic boutons. Furthermore, we show that α-synuclein-induced mild pathology in a mouse model of Parkinson’s disease enhances microglial engulfment of these boutons. These findings suggest that the activation state of dopaminergic neurons and their synaptic terminals may act as a critical cue for microglial recognition and engulfment. Our study highlights the microglial finetuning of dopaminergic synapses and implicates microglia in the early stage of Parkinson’s disease.