title: Ethanol increases GABAergic transmission and excitability in cerebellar molecular layer interneurons from GAD67-GFP knock-in mice.
abstract: OBJECTIVE
  This 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.
  
  
  METHODS
  Transgenic 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.
  
  
  RESULTS
  Stellate 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.
  
  
  CONCLUSIONS
  Ethanol 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.
authors.affiliation: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Wadleigh
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D055879:Gene Knock-In Techniques; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D049452:Green Fluorescent Proteins; D000431:Ethanol; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
references.citation: Br J Pharmacol. 1998 Nov;125(6):1375-81
references.pmid: 9863670
references.citation: Neuron. 1993 Nov;11(5):885-93
references.pmid: 8240811
references.citation: J Physiol. 2004 Feb 1;554(Pt 3):707-20
references.pmid: 14617674
references.citation: J Cell Biol. 1972 May;53(2):271-89
references.pmid: 4537207
references.citation: J Neurophysiol. 2006 Feb;95(2):700-8
references.pmid: 16251261
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):769-74
references.pmid: 18184813
references.citation: Neuropharmacology. 2009 Aug;57(2):109-20
references.pmid: 19426745
references.citation: Prog Neurobiol. 2006 Feb-Apr;78(3-5):272-303
references.pmid: 16759785
references.citation: Int Rev Neurobiol. 2010;91:339-72
references.pmid: 20813248
references.citation: Cerebellum. 2008;7(3):332-47
references.pmid: 18418667
references.citation: Brain Res Rev. 2011 Jan 1;65(2):113-23
references.pmid: 20837058
references.citation: J Physiol. 1993 Aug;468:177-200
references.pmid: 7504726
references.citation: Methods. 1999 Jun;18(2):144-9
references.pmid: 10356344
references.citation: J Pharmacol Exp Ther. 2007 Oct;323(1):356-64
references.pmid: 17652632
references.citation: J Comp Neurol. 2003 Dec 1;467(1):60-79
references.pmid: 14574680
references.citation: Nat Neurosci. 2009 Aug;12(8):1042-9
references.pmid: 19578381
references.citation: J Neurophysiol. 2002 Jan;87(1):183-90
references.pmid: 11784741
references.citation: Neuron. 2008 Jun 12;58(5):763-74
references.pmid: 18549787
references.citation: Trends Neurosci. 2010 Nov;33(11):524-32
references.pmid: 20869126
references.citation: Can J Physiol Pharmacol. 1985 Sep;63(9):1075-9
references.pmid: 2864993
references.citation: J Neurosci. 1989 Jun;9(6):2141-50
references.pmid: 2723768
references.citation: Neuropsychopharmacology. 2010 Aug;35(9):1984-96
references.pmid: 20520600
references.citation: J Neurosci. 2010 Jun 16;30(24):8171-9
references.pmid: 20554867
references.citation: Neurosci Biobehav Rev. 2008;32(3):466-85
references.pmid: 17919727
references.citation: Neuron. 2008 Jun 12;58(5):655-8
references.pmid: 18549777
references.citation: PLoS One. 2010 Aug 12;5(8):e12119
references.pmid: 20711348
references.citation: J Pharmacol Exp Ther. 2008 Dec;327(3):910-7
references.pmid: 18755936
references.citation: J Physiol. 1998 May 15;509 ( Pt 1):221-32
references.pmid: 9547395
references.citation: Alcohol Clin Exp Res. 2006 Aug;30(8):1400-7
references.pmid: 16899043
references.citation: Nat Neurosci. 2006 Jun;9(6):798-806
references.pmid: 16680164
references.citation: J Neurosci. 2003 Oct 22;23(29):9620-31
references.pmid: 14573542
references.citation: Alcohol. 2007 May;41(3):187-99
references.pmid: 17521847
references.citation: Prog Brain Res. 2005;148:181-8
references.pmid: 15661190
references.citation: Neuron. 1997 Sep;19(3):665-78
references.pmid: 9331356
references.citation: Can J Physiol Pharmacol. 1980 Nov;58(11):1342-6
references.pmid: 6260317