title: 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 GABA(A) 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 GABA(A) receptors and also increases the frequency of spontaneous inhibitory postsynaptic currents mediated by synaptic GABA(A) 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 GABA(A) 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 GABA(A) receptor-mediated transmission and highlight potential areas where future research is needed.
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA, cfvalenzuela@msn.com.
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
authors.forename: Karick
authors.initials: K
authors.lastname: Jotty
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D009415:Nerve Net / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D011963:Receptors, GABA-A; D000431:Ethanol