TY - JOUR
T1 - Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release
AU - Ye, Liang
AU - Orynbayev, Murat
AU - Zhu, Xiangyu
AU - Lim, Eunice Y.
AU - Dereddi, Ram R.
AU - Agarwal, Amit
AU - Bergles, Dwight E.
AU - Bhat, Manzoor A.
AU - Paukert, Martin
N1 - Funding Information:
The authors would like to thank Priscilla M. Barba-Escobedo, John Cavaretta, and Naiqing Ye for expert support in genotyping and animal husbandry, and Drs. Louis Reichardt and Jason Pugh for sharing the Tg(mα6-cre)B1LFR mouse line. A.A. is supported by the Chica and Heinz Schaller Research Foundation and grant A09N/SFB1158 from the Deutsche Forschungsgemeinschaft. This work was supported by R01MH083728 to D.E.B., and R01AA025128, R01MH113780, and The Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation to M.P.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-19475-5
DO - 10.1038/s41467-020-19475-5
M3 - Article
C2 - 33268792
AN - SCOPUS:85097024176
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6157
ER -