Functional activation of dorsal striatum astrocytes improves movement deficits in hemi-parkinsonian mice

Summary Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source of striatal network modulation. However, it remains unknown how dopamine loss affects striatal astrocyte activity and whether astrocyte activity regulates behavioral deficits in PD. We addressed these questions by performing astrocyte-specific calcium recordings and manipulations using in vivo fiber photometry and chemogenetics. We find that locomotion elicits astrocyte calcium activity over a slower timescale than neurons. Unilateral dopamine depletion reduced locomotion-related astrocyte responses. Chemogenetic activation facilitated astrocyte activity, and improved asymmetrical motor deficits and open field exploratory behavior in dopamine lesioned mice. Together, our results establish a novel role for functional striatal astrocyte signaling in modulating motor function in PD and highlight non-neuronal targets for potential PD therapeutics.