151. Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior.
- Author
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Yu, Xinzhu, Taylor, Anna MW, Nagai, Jun, Golshani, Peyman, Evans, Christopher J, Coppola, Giovanni, and Khakh, Baljit S
- Subjects
Corpus Striatum ,Astrocytes ,Neurons ,Animals ,Mice ,Transgenic ,Humans ,Huntington Disease ,Calcium ,Behavior ,Animal ,Calcium Signaling ,GABA Plasma Membrane Transport Proteins ,Genetics ,Neurosciences ,Psychology ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Astrocytes tile the central nervous system, but their functions in neural microcircuits in vivo and their roles in mammalian behavior remain incompletely defined. We used two-photon laser scanning microscopy, electrophysiology, MINIscopes, RNA-seq, and a genetic approach to explore the effects of reduced striatal astrocyte Ca2+ signaling in vivo. In wild-type mice, reducing striatal astrocyte Ca2+-dependent signaling increased repetitive self-grooming behaviors by altering medium spiny neuron (MSN) activity. The mechanism involved astrocyte-mediated neuromodulation facilitated by ambient GABA and was corrected by blocking astrocyte GABA transporter 3 (GAT-3). Furthermore, in a mouse model of Huntington's disease, dysregulation of GABA and astrocyte Ca2+ signaling accompanied excessive self-grooming, which was relieved by blocking GAT-3. Assessments with RNA-seq revealed astrocyte genes and pathways regulated by Ca2+ signaling in a cell-autonomous and non-cell-autonomous manner, including Rab11a, a regulator of GAT-3 functional expression. Thus, striatal astrocytes contribute to neuromodulation controlling mouse obsessive-compulsive-like behavior.
- Published
- 2018