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

Abstract

Microglia, the resident immune cells of the brain, are essential for maintaining the homeostasis of the central nervous system and play a crucial role in either the protection or progression of neurodegenerative diseases. To fulfill these functions, they must detect and respond to environmental changes, including fluctuations in neuronal activity. Recent studies have indicated that microglia also respond to classical signaling substances in the brain, such as the neurotransmitters glutamate, GABA, and norepinephrine (NE). However, the involvement of microglia in dopaminergic signaling remains largely unknown. In this study, we found that microglia and dopamine boutons are located in close proximity and that microglia express dopamine D1 and D2 receptors, enabling them to react to nearby dopamine. In addition, microglia-specific deletion of the dopamine D2 receptor reduced microglia numbers, altered their morphology, and changed cytokine expression in the striatum. We further found that the knockout of the D2 receptor in microglia gives rise to deficits in motor-related behaviors. Our findings suggest that microglial dopamine receptors may be important for striatal functions and motor-related behaviors.