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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-Agonists / pharmacology*
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Alcoholic Intoxication / genetics
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Alcoholic Intoxication / metabolism
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Alcoholic Intoxication / physiopathology
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism
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Calcium / metabolism*
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Cerebellum / cytology
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Cerebellum / drug effects
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Cerebellum / metabolism
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Ethanol / pharmacology*
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Excitatory Amino Acid Transporter 1 / deficiency
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Excitatory Amino Acid Transporter 1 / genetics
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Female
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Gene Expression Regulation
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Locomotion / drug effects
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Locomotion / physiology
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Male
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Mice
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Mice, Knockout
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Microscopy, Fluorescence, Multiphoton
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Neurogenesis / drug effects
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Neurogenesis / genetics
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Norepinephrine / antagonists & inhibitors
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Norepinephrine / pharmacology*
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Receptors, Adrenergic, alpha-1 / deficiency
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Receptors, Adrenergic, alpha-1 / genetics
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Wakefulness / drug effects*
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Wakefulness / physiology
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Zinc Finger Protein GLI1 / genetics
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Zinc Finger Protein GLI1 / metabolism
Substances
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Adra1a protein, mouse
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Adrenergic alpha-Agonists
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Excitatory Amino Acid Transporter 1
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Gli1 protein, mouse
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Receptors, Adrenergic, alpha-1
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Slc1a3 protein, mouse
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Zinc Finger Protein GLI1
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Ethanol
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Calcium
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Norepinephrine