Alcohol potently modulates climbing fiber-->Purkinje neuron synapses: role of metabotropic glutamate receptors.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D4375B6ECBBD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Alcohol potently modulates climbing fiber-->Purkinje neuron synapses: role of metabotropic glutamate receptors.
Journal
The Journal of neuroscience
Author(s)
Carta M., Mameli M., Valenzuela C.F.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Publication state
Published
Issued date
15/02/2006
Peer-reviewed
Oui
Volume
26
Number
7
Pages
1906-1912
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Abstract
Consumption of alcoholic beverages produces alterations in motor coordination and equilibrium that are responsible for millions of accidental deaths. Studies indicate that ethanol produces these alterations by affecting the cerebellum, a brain region involved in the control of motor systems. Purkinje neurons of the cerebellar cortex have been shown to be particularly important targets of ethanol. However, its mechanism of action at these neurons is poorly understood. We hypothesized that ethanol could modulate Purkinje neuron function by altering the excitatory input provided by the climbing fiber from the inferior olive, which evokes a powerful all-or-none response denoted as the complex spike. To test this hypothesis, we performed whole-cell patch-clamp electrophysiological and Ca2+ imaging experiments in acute slices from rat cerebella. We found that ethanol potently inhibits the late phase of the complex spike and that this effect is the result of inhibition of type-1 metabotropic glutamate receptor-dependent responses at the postsynaptic level. Moreover, ethanol inhibited climbing fiber long-term depression, a form of synaptic plasticity that also depends on activation of these metabotropic receptors. Our findings identify the climbing fiber-->Purkinje neuron synapse as an important target of ethanol in the cerebellar cortex and indicate that ethanol significantly affects cerebellar circuits even at concentrations as low as 10 mm (legal blood alcohol level in the United States is below 0.08 g/dl = 17 mm).

Keywords
Alanine/analogs & derivatives, Alanine/pharmacology, Animals, Aspartic Acid/pharmacology, Disease Models, Animal, Ethanol/pharmacology, Long-Term Synaptic Depression/drug effects, Male, Nerve Fibers/drug effects, Nerve Fibers/physiology, Patch-Clamp Techniques, Purkinje Cells/drug effects, Purkinje Cells/physiology, Quinoxalines/pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate/drug effects, Receptors, Metabotropic Glutamate/physiology, Synapses/drug effects, Synapses/physiology, Xanthenes/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
03/02/2017 12:18
Last modification date
20/08/2019 16:54
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