• Alcohol Alcohol. · Jan 2012

    Ethanol increases GABAergic transmission and excitability in cerebellar molecular layer interneurons from GAD67-GFP knock-in mice.

    • Aya Wadleigh and C Fernando Valenzuela.
    • Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
    • Alcohol Alcohol. 2012 Jan 1;47(1):1-8.

    AimsThis study assessed the acute effect of ethanol on GABAergic transmission at molecular layer interneurons (MLIs; i.e. basket and stellate cells) in the cerebellar cortex. The actions of ethanol on spontaneous firing of these pacemaker neurons were also measured.MethodsTransgenic mice (glutamic acid-decarboxylase 67-green fluorescent protein knock-in mice) that express green fluorescence protein in GABAergic interneurons were used to aid in the identification of MLIs. Parasagittal cerebellar slices were prepared and whole-cell patch-clamp electrophysiological techniques were used to measure GABA(A) receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). Loose-seal cell-attached recordings were used to measure spontaneous action potential firing.ResultsStellate cells received spontaneous GABAergic input in the form of a mixture of action potential-dependent events (sIPSCs) and quantal events (mIPSCs); ethanol increased sIPSC frequency to a greater extent than mIPSC frequency. Ethanol increased spontaneous action potential firing of MLIs, which could explain the increase in sIPSC frequency in stellate cells. Basket cells received GABAergic input in the form of quantal events only. Ethanol significantly increased the frequency of these events, which may be mediated by a different type of interneuron (perhaps, the Lugaro cell) or Purkinje cell collaterals.ConclusionsEthanol exposure differentially increases GABA release at stellate cell vs. basket cell-to-Purkinje cell synapses. This effect may contribute to the abnormalities in cerebellar function associated with alcohol intoxication.

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