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Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release

Liang Ye, Murat Orynbayev, Xiangyu Zhu, Eunice Y. Lim, Ram R. Dereddi, Amit Agarwal, Dwight E. Bergles, Manzoor A. Bhat and Martin Paukert ()
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Liang Ye: University of Texas Health Science Center at San Antonio
Murat Orynbayev: University of Texas Health Science Center at San Antonio
Xiangyu Zhu: University of Texas Health Science Center at San Antonio
Eunice Y. Lim: University of Texas Health Science Center at San Antonio
Ram R. Dereddi: Heidelberg University
Amit Agarwal: Heidelberg University
Dwight E. Bergles: Johns Hopkins University School of Medicine
Manzoor A. Bhat: University of Texas Health Science Center at San Antonio
Martin Paukert: University of Texas Health Science Center at San Antonio

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: Abstract 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 Ca2+ elevations during vigilance, are not well understood. Using in vivo two-photon imaging, we show that locomotion-induced Ca2+ 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 α1A-adrenergic receptor from astroglia, indicating that norepinephrine acts directly on these ubiquitous glial cells. Ethanol reduces vigilance-dependent Ca2+ 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 Ca2+ activation does not affect motor coordination, global suppression of astroglial networks may contribute to the cognitive effects of alcohol intoxication.

Date: 2020
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DOI: 10.1038/s41467-020-19475-5

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