Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Nat Commun. 2020 Dec 2;11(1):6157. doi: 10.1038/s41467-020-19475-5.
Norepinephrine adjusts sensory processing in cortical networks and gates plasticity enabling adaptive behavior. The actions of norepinephrine are profoundly altered by recreational drugs like ethanol, but the consequences of these changes on distinct targets such as astrocytes, which exhibit norepinephrine-dependent Ca elevations during vigilance, are not well understood. Using in vivo two-photon imaging, we show that locomotion-induced Ca elevations in mouse astroglia are profoundly inhibited by ethanol, an effect that can be reversed by enhancing norepinephrine release. Vigilance-dependent astroglial activation is abolished by deletion of α-adrenergic receptor from astroglia, indicating that norepinephrine acts directly on these ubiquitous glial cells. Ethanol reduces vigilance-dependent Ca transients in noradrenergic terminals, but has little effect on astroglial responsiveness to norepinephrine, suggesting that ethanol suppresses their activation by inhibiting norepinephrine release. Since abolition of astroglia Ca activation does not affect motor coordination, global suppression of astroglial networks may contribute to the cognitive effects of alcohol intoxication.
去甲肾上腺素调节皮质网络中的感觉处理，并开启可塑性，从而实现适应性行为。去甲肾上腺素的作用被像乙醇这样的娱乐性药物深刻地改变了，但是这些变化对特定目标的后果，如在警觉期间表现出依赖去甲肾上腺素的 Ca 升高的星形胶质细胞，还不是很清楚。使用活体双光子成像，我们显示，在小鼠星形胶质细胞中，运动诱导的 Ca 升高被乙醇深刻抑制，这种效应可以通过增强去甲肾上腺素的释放来逆转。通过从星形胶质细胞中删除α肾上腺素受体，警觉依赖的星形胶质细胞激活被消除，表明去甲肾上腺素直接作用于这些普遍存在的胶质细胞。乙醇减少了去甲肾上腺素末梢中警觉依赖性的 Ca 瞬变，但对星形胶质细胞对去甲肾上腺素的反应性几乎没有影响，这表明乙醇通过抑制去甲肾上腺素的释放来抑制它们的激活。由于星形胶质细胞 Ca 激活的消除不影响运动协调，因此星形胶质细胞网络的全局抑制可能导致酒精中毒的认知影响。
