α1-Adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice.
α1-Adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice.
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DOI：
10.1016/j.ceca.2013.09.001
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发表时间：
2013-12
期刊：
影响因子：
4
通讯作者：
Nedergaard M
中科院分区：
文献类型：
--
作者：
Ding F;O'Donnell J;Thrane AS;Zeppenfeld D;Kang H;Xie L;Wang F;Nedergaard M
清醒行为小鼠中星形胶质细胞Ca 2+信号是广泛的，协调的，从根本上不同于离体和麻醉动物中观察到的局部限制性Ca 2+瞬变。在这里，我们表明，同步释放的去甲肾上腺素（NE）从蓝斑（LC）的投射在整个大脑皮层介导的长距离Ca 2+信号通过激活星形胶质细胞α1-肾上腺素能受体。当LC输出被触发的生理感觉（胡须）刺激或喷气惊吓反应，星形胶质细胞响应快速Ca 2+瞬变，包括整个成像领域（位于额叶或顶叶皮层）。肾上腺素能抑制剂（包括α1-肾上腺素能拮抗剂哌唑嗪）的应用有效抑制了诱发的以及经常观察到的自发性星形胶质细胞Ca 2+信号。LC特异性神经毒素N-（2-氯乙基）-N-乙基-2-溴苄胺（DSP-4）使皮质NE含量降低> 90%，阻止清醒小鼠中几乎所有星形胶质细胞Ca 2+信号。观察结果表明，在成年，未麻醉的小鼠，星形胶质细胞不直接响应感觉刺激诱发的神经元能信号。相反，星形胶质细胞似乎是NE的主要靶点，星形胶质细胞Ca 2+信号传导由α1-肾上腺素能受体触发。反过来，星形胶质细胞可以协调神经调质对神经元活性的广泛影响。
Astrocyte Ca2+ signals in awake behaving mice are widespread, coordinated and differ fundamentally from the locally restricted Ca2+ transients observed ex vivo and in anesthetized animals. Here we show that the synchronized release of norepinephrine (NE) from locus coeruleus (LC) projections throughout the cerebral cortex mediate long-ranging Ca2+ signals by activation of astrocytic α1-adrenergic receptors. When LC output was triggered by either physiological sensory (whisker) stimulation or an air-puff startle response, astrocytes responded with fast Ca2+ transients that encompassed the entire imaged field (positioned over either frontal or parietal cortex). The application of adrenergic inhibitors, including α1-adrenergic antagonist prazosin, potently suppressed both evoked, as well as the frequently observed spontaneous astroglial Ca2+ signals. The LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which reduced cortical NE content by >90%, prevented nearly all astrocytic Ca2+ signals in awake mice. The observations indicate that in adult, unanesthetized mice, astrocytes do not respond directly to glutamatergic signaling evoked by sensory stimulation. Instead astrocytes appear to be the primary target for NE, with astrocytic Ca2+ signaling being triggered by the α1-adrenergic receptor. In turn, astrocytes may coordinate the broad effects of neuromodulators on neuronal activity.
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