Locus Coeruleus α-Adrenergic-Mediated Activation of Cortical Astrocytes In Vivo
Locus Coeruleus α-Adrenergic-Mediated Activation of Cortical Astrocytes In Vivo
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DOI：
10.1093/cercor/bhn040
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发表时间：
2008-12-01
期刊：
影响因子：
3.7
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
--
作者：
Bekar, Lane K.;He, Wei;Nedergaard, Maiken
蓝斑（LC）为皮层提供去甲肾上腺素（NE）的唯一来源，以调节皮层突触活动，从而响应显著的感觉信息。NE已被证明可以改善信噪比，锐化感受野，并在学习，记忆和认知表现中发挥作用。虽然LC介导的神经元的影响已得到解决，星形胶质细胞的参与迄今尚未被证明在这些神经调节功能。在这里，我们第一次在活体小鼠中显示，星形胶质细胞对LC的电刺激表现出快速的Ca 2+增加。此外，已知导致阶段性LC活性的强外周刺激导致整个感觉皮层中星形胶质细胞中的Ca 2+反应，其独立于感觉驱动的谷氨酸依赖性途径。此外，星形胶质细胞Ca 2+瞬变由已知影响LC输出的α（2）-特异性激动剂/拮抗剂组合竞争性调节，对LC-特异性神经毒素N-（2-氯乙基）-N-乙基-2-溴苄胺敏感，并被α-肾上腺素能拮抗剂局部抑制。因此，LC功能的未来研究必须考虑LC神经调节作用部分来自星形胶质细胞活化的可能性。
The locus coeruleus (LC) provides the sole source of norepinephrine (NE) to the cortex for modulation of cortical synaptic activity in response to salient sensory information. NE has been shown to improve signal-to-noise ratios, sharpen receptive fields and function in learning, memory, and cognitive performance. Although LC-mediated effects on neurons have been addressed, involvement of astrocytes has thus far not been demonstrated in these neuromodulatory functions. Here we show for the 1st time in live mice, that astrocytes exhibit rapid Ca2+ increases in response to electrical stimulation of the LC. Additionally, robust peripheral stimulation known to result in phasic LC activity leads to Ca2+ responses in astrocytes throughout sensory cortex that are independent of sensory-driven glutamate-dependent pathways. Furthermore, the astrocytic Ca2+ transients are competitively modulated by alpha(2)-specific agonist/antagonist combinations known to impact LC output, are sensitive to the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, and are inhibited locally by an alpha-adrenergic antagonist. Future investigations of LC function must therefore consider the possibility that LC neuromodulatory effects are in part derived from activation of astrocytes.