GSE114756
Reducing astrocyte calcium signaling in vivo alters striatal microcircuits and causes repetitive behavior II
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 2-photon laser scanning microscopy (2PLSM), electrophysiology, MINIscopes, RNA-seq and a new genetic approach to characterize 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 mediated 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 obsessive-compulsive-like behavior in mice. Overall design: Total 16 samples were used in this data set. Whole striata were extraced from 8 adult Aldh1l1-Cre/ERT2 x Ribotag mice: 4 mice received AAV encoding a control protein and 4 mice received AAV encoding a protein that suppresses calcium signals named hPMCA2w/b. After homogenization, RNA was purified from (i) cleared lysate as the input and control, and (ii) astrocyte-specific ribosome-associated RNA precipitated via a hemagglutinin (HA) tag.