Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex—Recent Advances

Abstract

Studies from several laboratories have shown that ethanol impairs cerebellar function, in part, by altering GABAergic transmission. Here, we discuss recent advances in our understanding of the acute effects of ethanol on GABAA receptor-mediated neurotransmission at cerebellar cortical circuits, mainly focusing on electrophysiological studies with slices from laboratory animals. These studies have shown that acute ethanol exposure increases GABA release at molecular layer interneuron-to-Purkinje cell synapses and also at reciprocal synapses between molecular layer interneurons. In granule cells, studies with rat cerebellar slices have consistently shown that acute ethanol exposure both potentiates tonic currents mediated by extrasynaptic GABAA receptors and also increases the frequency of spontaneous inhibitory postsynaptic currents mediated by synaptic GABAA receptors. These effects have been also documented in some granule cells from mice and nonhuman primates. Currently, there are two distinct models on how ethanol produces these effects. In one model, ethanol primarily acts by directly potentiating extrasynaptic GABAA receptors, including a population that excites granule cell axons and stimulates glutamate release onto Golgi cells. In the other model, ethanol acts indirectly by increasing spontaneous Golgi cell firing via inhibition of the Na+/K+ ATPase, a quinidine-sensitive K+ channel, and neuronal nitric oxide synthase. It was also demonstrated that a direct inhibitory effect of ethanol on tonic currents can be unmasked under conditions of low protein kinase C activity. In the last section, we briefly discuss studies on the chronic effect of ethanol on cerebellar GABAA receptor-mediated transmission and highlight potential areas where future research is needed.

DOI: 10.1007/s12311-014-0639-3

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@article{Valenzuela2014MiniReviewEO, title={Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex—Recent Advances}, author={Carlos Fernando Valenzuela and Karick Jotty}, journal={The Cerebellum}, year={2014}, volume={14}, pages={438-446} }