The role of dopamine receptors on microglial functions and motor related behaviors

Abstract

Microglia, the resident immune cells of the brain, play a key role in maintaining central nervous system homeostasis and are implicated in various neurodegenerative and psychiatric disorders. To fulfill these roles, microglia must detect and respond to environmental changes, including neuronal activity. While recent studies have shown microglial responses to classical neurotransmitters like glutamate, GABA, and norepinephrine, their role in dopaminergic signaling remains unclear. Here, we demonstrate that microglia are closely associated with dopamine boutons and express dopamine D1 and D2 receptors, enabling them to respond to dopamine signals. Additionally, microgliaspecific deletion of the D2 receptor reduced microglial numbers, altered morphology, and changed cytokine expression. These microglial alterations weakened the extracellular matrix and reduced the excitability of parvalbumin (PV) interneurons in the striatum. Furthermore, changes in PV interneuron-derived inhibitory synapses led to deficits in motorrelated behaviors. Our findings highlight the significance of dopamine receptor-mediated signaling in microglia for striatal synaptic functions and motor-related behaviors.