2021 Seed Grant
Rafiq Huda, Ph.D.
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate the activity of downstream motor structures. In agreement, dysfunction of the striatum is a key contributor to the motor symptoms of Parkinson’s disease (PD), a neurodegenerative disorder characterized by the loss of dopamine producing neurons. Astrocytes are an integral component of brain circuits that modulate neuronal processing and behavioral output via multiple mechanisms. Although deficits in striatal neurons in animal models of PD are well-characterized, how loss of dopamine affects the function of astrocytes in vivo remains unknown. As a result, striatal astrocyte signaling has been overlooked as a potential therapeutic target for the motor symptoms of PD. We have pioneered the technologies necessary to address this major knowledge gap in our biological understanding of PD. In this project, we will use cutting-edge in vivo microscopy, genetics, behavioral, and computational approaches to test the hypothesis that astrocytes orchestrate the network activity of striatal neurons to facilitate movement and that dysregulation of this process contributes to the motor symptoms of PD. Together, our work will establish novel roles for astrocytes in the neuromodulation of striatal circuits, paving the way for next-generation astrocyte-targeted therapies for PD and other striatum-dependent movement disorders.