Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability.

Details

Serval ID
serval:BIB_2E112F4AFA1B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability.
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
14/04/2004
Peer-reviewed
Oui
Volume
24
Number
15
Pages
3746-3751
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Alcohol intoxication alters coordination and motor skills, and this is responsible for a significant number of traffic accident-related deaths around the world. Although the precise mechanism of action of ethanol (EtOH) is presently unknown, studies suggest that it acts, in part, by interfering with normal cerebellar functioning. An important component of cerebellar circuits is the granule cell. The excitability of these abundantly expressed neurons is controlled by the Golgi cell, a subtype of GABAergic interneuron. Granule cells receive GABAergic input in the form of phasic and tonic currents that are mediated by synaptic and extrasynaptic receptors, respectively. Using the acute cerebellar slice preparation and patch-clamp electrophysiological techniques, we found that ethanol induces a parallel increase in both the frequency of spontaneous IPSCs and the magnitude of the tonic current. EtOH (50 mm) did not produce this effect when spontaneous action potentials were blocked with tetrodotoxin. Recordings in the loose-patch cell-attached configuration demonstrated that ethanol increases the frequency of spontaneous action potentials in Golgi cells. Taken together, these findings indicate that ethanol enhances GABAergic inhibition of granule cells via a presynaptic mechanism that involves an increase in action potential-dependent GABA release from Golgi cells. This effect is likely to have an impact on the flow of information through the cerebellar cortex and may contribute to the mechanism by which acute ingestion of alcoholic beverages induces motor impairment.

Keywords
Alcoholic Intoxication/physiopathology, Animals, Cerebellum/cytology, Cerebellum/drug effects, Cerebellum/physiology, Dose-Response Relationship, Drug, Ethanol/pharmacology, Excitatory Amino Acid Antagonists/pharmacology, Excitatory Postsynaptic Potentials/drug effects, GABA Antagonists/pharmacology, In Vitro Techniques, Interneurons/classification, Interneurons/drug effects, Interneurons/physiology, Male, Neural Inhibition/drug effects, Neurons/drug effects, Neurons/physiology, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Synaptic Transmission/drug effects, gamma-Aminobutyric Acid/metabolism
Pubmed
Web of science
Create date
03/02/2017 11:31
Last modification date
20/08/2019 13:12
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