Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior.
Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior.
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DOI：
10.1016/j.neuron.2018.08.015
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发表时间：
2018-09-19
期刊：
影响因子：
16.2
通讯作者：
Khakh BS
中科院分区：
文献类型：
--
作者：
Yu X;Taylor AMW;Nagai J;Golshani P;Evans CJ;Coppola G;Khakh BS
星形胶质细胞负责中枢神经系统，但它们在体内神经微电路中的功能以及它们在哺乳动物行为中的作用仍未完全确定。我们使用 2 光子激光扫描显微镜、电生理学、MINIscopes、RNA-seq 和遗传方法来探索体内纹状体星形胶质细胞 Ca2+ 信号传导减少的影响。在野生型小鼠中，减少纹状体星形胶质细胞 Ca2+ 依赖性信号传导可通过改变中棘神经元 (MSN) 活性来增加重复的自我梳理行为。该机制涉及由环境 GABA 介导的星形胶质细胞介导的神经调节，并通过阻断星形胶质细胞 GABA 转运蛋白 3 (GAT-3) 来纠正。此外，在亨廷顿病小鼠模型中，GABA 和星形胶质细胞 Ca2+ 信号传导失调伴随着过度的自我修饰，而阻断 GAT-3 可以缓解这种情况。 RNA-seq 评估揭示了星形胶质细胞基因和通路以细胞自主和非细胞自主的方式受 Ca2+ 信号传导调节，包括 Rab11a（GAT-3 功能表达的调节因子）。因此，纹状体星形胶质细胞有助于控制小鼠强迫性行为的神经调节。 Khakh 实验室评估了成年小鼠纹状体体内星形胶质细胞钙信号传导减弱的后果。他们发现了过度的自我修饰表型，并在分子、细胞和体内水平上探索了其机制。
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, 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 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 mouse obsessive-compulsive-like behavior. The Khakh laboratory evaluated the consequences of genetically attenuating astrocyte calcium signaling in the adult mouse striatum in vivo. They discovered excessive self-grooming phenotypes, the mechanisms of which were explored at molecular, cellular and in vivo levels.
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影响因子：
16.2
作者：
Haustein MD;Kracun S;Lu XH;Shih T;Jackson-Weaver O;Tong X;Xu J;Yang XW;O'Dell TJ;Marvin JS;Ellisman MH;Bushong EA;Looger LL;Khakh BS
通讯作者：
Khakh BS
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1038/npp.2015.26
发表时间：
2015-06
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Aida T;Yoshida J;Nomura M;Tanimura A;Iino Y;Soma M;Bai N;Ito Y;Cui W;Aizawa H;Yanagisawa M;Nagai T;Takata N;Tanaka KF;Takayanagi R;Kano M;Götz M;Hirase H;Tanaka K
通讯作者：
Tanaka K
影响因子：
5.3
作者：
Jiang, Ruotian;Diaz-Castro, Blanca;Khakh, Baljit S.
通讯作者：
Khakh, Baljit S.
影响因子：
14.8
作者：
Kalueff, Allan V.;Aldridge, J. Wayne;Tuohimaa, Pentti
通讯作者：
Tuohimaa, Pentti