Alcohol Enhances GABAergic Transmission to Cerebellar Granule Cells via an Increase in Golgi Cell Excitability
Journal of Neuroscience. 2004-04-14; 24(15): 3746-3751
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1. J Neurosci. 2004 Apr 14;24(15):3746-51.
Alcohol enhances GABAergic transmission to cerebellar granule cells via an
increase in Golgi cell excitability.
Carta M(1), Mameli M, Valenzuela CF.
(1)Department of Neurosciences, University of New Mexico Health Sciences Center,
Albuquerque, New Mexico 87131, USA.
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.
PMID: 15084654 [Indexed for MEDLINE]