Purkinje cell dopaminergic inputs to astrocytes regulate cerebellar-dependent behavior

Abstract

Abstract Dopamine has a significant role in motor and cognitive function. The dopaminergic pathways originating from the midbrain have received the most attention; however, the relevance of the cerebellar dopaminergic system is largely undiscovered. Here, we show that the major cerebellar astrocyte type Bergmann glial cells express D1 receptors. Dopamine can be synthesized in Purkinje cells by cytochrome P450 and released in an activity-dependent fashion. We demonstrate that activation of D1 receptors induces membrane depolarization and Ca 2+ release from the internal store. These astrocytic activities in turn modify Purkinje cell output by altering its excitatory and inhibitory synaptic input. Lastly, we show that conditional knockout of D1 receptors in Bergmann glial cells results in decreased locomotor activity and impaired social activity. These results contribute to the understanding of the molecular, cellular, and circuit mechanisms underlying dopamine function in the cerebellum, revealing a critical role for the cerebellar dopaminergic system in motor and social behavior.