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Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior

机译:减少体内的星形胶质细胞钙信号传递改变纹状体微电路并导致重复行为

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摘要

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.
机译:星形胶质细胞瓷砖中枢神经系统,但它们在体内神经微电路的功能及其在哺乳动物行为中的作用仍然不完全定义。我们使用了双光子激光扫描显微镜,电生理学,Miniscopes,RNA-SEQ,以及遗传方法来探讨减少纹纹体星形胶质细胞Ca2 +信号传导在体内的影响。在野生型小鼠中,通过改变培养基刺神经元(MSN)活性,减少纹纹体星形胶质细胞CA2 +依赖性信号传导增加的重复自整体行为。该机制涉及通过环境GABA促进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)来校正。此外,在亨廷顿疾病的小鼠模型中,GABA和星形胶质细胞CA2 +信号传导的失调过度自我修饰,通过阻断GAT-3来缓解。具有RNA-SEQ的评估显示通过CA2 +信号传导以细胞 - 自主和非细胞 - 自主方式调节的星形胶质细胞基因和途径,包括Rab11a,一种用于GAT-3功能表达的调节剂。因此,纹状体星形胶质细胞有助于治疗小鼠强迫性诱导的行为的神经调节。

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  • 来源
    《Neuron》 |2018年第6期|共18页
  • 作者单位

    Univ Calif Los Angeles David Geffen Sch Med Dept Physiol Los Angeles CA 90095 USA;

    Univ Calif Los Angeles David Geffen Sch Med Semel Inst Neurosci &

    Human Behav Hatos Ctr;

    Univ Calif Los Angeles David Geffen Sch Med Dept Physiol Los Angeles CA 90095 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Neurol Los Angeles CA 90095 USA;

    Univ Calif Los Angeles David Geffen Sch Med Semel Inst Neurosci &

    Human Behav Hatos Ctr;

    Univ Calif Los Angeles David Geffen Sch Med Dept Neurol Los Angeles CA 90095 USA;

    Univ Calif Los Angeles David Geffen Sch Med Dept Physiol Los Angeles CA 90095 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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