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

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 norepin...

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Main Authors: Ye, Liang (Author) , Orynbayev, Murat (Author) , Zhu, Xiangyu (Author) , Lim, Eunice Y. (Author) , Dereddi, Ram (Author) , Agarwal, Amit (Author) , Bergles, Dwight E. (Author) , Bhat, Manzoor A. (Author) , Paukert, Martin (Author)
Format: Article (Journal)
Language:English
Published: 02 December 2020
In: Nature Communications
Year: 2020, Volume: 11
ISSN:2041-1723
DOI:10.1038/s41467-020-19475-5
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-020-19475-5
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-020-19475-5
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Author Notes:Liang Ye, Murat Orynbayev, Xiangyu Zhu, Eunice Y. Lim, Ram R. Dereddi, Amit Agarwal, Dwight E. Bergles, Manzoor A. Bhat, & Martin Paukert
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Summary: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.
Item Description:Gesehen am 19.01.2021
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-020-19475-5