| First Author | Yu X | Year | 2018 |
| Journal | Neuron | Volume | 99 |
| Issue | 6 | Pages | 1170-1187.e9 |
| PubMed ID | 30174118 | Mgi Jnum | J:270040 |
| Mgi Id | MGI:6269318 | Doi | 10.1016/j.neuron.2018.08.015 |
| Citation | Yu X, et al. (2018) Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior. Neuron 99(6):1170-1187.e9 |
| abstractText | 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 Ca(2+) signaling in vivo. In wild-type mice, reducing striatal astrocyte Ca(2+)-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 Ca(2+) signaling accompanied excessive self-grooming, which was relieved by blocking GAT-3. Assessments with RNA-seq revealed astrocyte genes and pathways regulated by Ca(2+) 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. |
