Ca(2+) signaling in astrocytes from Ip3r2(-/-) mice in brain slices and during startle responses in vivo.

Ca(2+) signaling in astrocytes from Ip3r2(-/-) mice in brain slices and during startle responses in vivo.
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来自IP3R2( - / - )小鼠的星形胶质细胞中的Ca(2+)脑切片中的CA(2+)信号传导。

DOI:
10.1038/nn.4001
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发表时间:
2015-05
影响因子:
25
通讯作者:
Khakh, Baljit S.
Khakh, Baljit S.
中科院分区:
医学1区
文献类型:
--
作者:
Srinivasan, Rahul;Huang, Ben S.;Venugopal, Sharmila;Johnston, April D.;Chai, Hua;Zeng, Hongkui;Golshani, Peyman;Khakh, Baljit S.

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细胞内钙信号被认为对星形胶质细胞在神经回路中的多种功能具有重要作用。然而,据报道,缺乏三磷酸肌醇2型受体(IP3R2)的小鼠缺乏星形胶质细胞的所有钙信号,但没有显示出神经元或神经血管缺陷,这意味着星形胶质细胞钙的波动在这些功能中没有作用(S)。一种假设是,体细胞钙波动的丢失也反映了星形胶质细胞突起中类似的丢失。在这里,我们测试了这一假设,发现星形胶质细胞内存在不同类型的钙波动,其中大多数发生在突起内,而不是在胞体内。这些波动被保存在IP3R2−/−小鼠的脑片和活体中,发生在末端足部,通过G蛋白偶联受体激活和惊吓诱导的神经调节反应而增加。我们的数据揭示了星形胶质细胞内新的钙波动,并突出了使用IP3R2−/−小鼠评估星形胶质细胞对神经回路功能和小鼠行为的贡献的研究的局限性。
Intracellular Ca2+ signaling is considered important for multiple astrocyte functions in neural circuits. However, mice devoid of inositol triphosphate type 2 receptors (IP3R2) reportedly lack all astrocyte Ca2+ signaling, but display no neuronal or neurovascular deficits, implying that astrocyte Ca2+ fluctuations play no role(s) in these functions. An assumption has been that loss of somatic Ca2+ fluctuations also reflects similar loss within astrocyte processes. Here, we tested this assumption and found diverse types of Ca2+ fluctuations within astrocytes, with most occurring within processes rather than in somata. These fluctuations were preserved in IP3R2−/− mice in brain slices and in vivo, occurred in endfeet, were increased by G-protein coupled receptor activation and by startle-induced neuromodulatory responses. Our data reveal novel Ca2+ fluctuations within astrocytes and highlight limitations of studies that used IP3R2−/− mice to evaluate astrocyte contributions to neural circuit function and mouse behavior.
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