Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642.
Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway.
Cell Calcium. 2013 Dec;54(6):387-94. doi: 10.1016/j.ceca.2013.09.001. Epub 2013 Sep 24.
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.
在清醒活动的小鼠中，星形胶质细胞 Ca2+ 信号广泛存在、协调一致，与在离体和麻醉动物中观察到的局部限制的 Ca2+ 瞬变有根本区别。在这里，我们表明蓝斑核（LC）投射到大脑皮层的去甲肾上腺素（NE）同步释放通过激活星形胶质细胞的α1-肾上腺素能受体来介导长程 Ca2+ 信号。当 LC 输出通过生理感觉（胡须）刺激或空气喷射惊跳反应触发时，星形胶质细胞会快速 Ca2+ 瞬变反应，包括整个成像区域（位于额叶或顶叶皮层上方）。应用肾上腺素能抑制剂，包括α1-肾上腺素能拮抗剂普萘洛尔，可以强烈抑制诱发的以及经常观察到的自发性星形胶质细胞 Ca2+ 信号。LC 特异性神经毒素 N-(2-氯乙基)-N-乙基-2-溴苯甲胺（DSP-4）可使皮质 NE 含量降低>90%，几乎阻止了清醒小鼠的所有星形胶质细胞 Ca2+ 信号。这些观察表明，在成年、未麻醉的小鼠中，星形胶质细胞不会直接对感觉刺激引起的谷氨酸能信号做出反应。相反，星形胶质细胞似乎是 NE 的主要靶标，α1-肾上腺素能受体触发星形胶质细胞 Ca2+ 信号。反过来，星形胶质细胞可能协调神经调质对神经元活动的广泛影响。
