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

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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.

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References

  1. Palmer MR, Hoffer BJ. GABAergic mechanisms in the electrophysiological actions of ethanol on cerebellar neurons. Neurochem Res. 1990;15(2):145–51.

    Article  CAS  PubMed  Google Scholar 

  2. Jaatinen P, Rintala J. Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum. Cerebellum. 2008;7(3):332–47 [Research Support, Non-U.S. Gov’t Review].

    Article  CAS  PubMed  Google Scholar 

  3. Botta P, Radcliffe RA, Carta M, Mameli M, Daly E, Floyd KL, et al. Modulation of GABA(A) receptors in cerebellar granule neurons by ethanol: a review of genetic and electrophysiological studies. Alcohol. 2007;41:187–99.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Palmer MR, van Horne CG, Harlan JT, Moore EA. Antagonism of ethanol effects on cerebellar Purkinje neurons by the benzodiazepine inverse agonists Ro 15–4513 and FG 7142: electrophysiological studies. J Pharmacol Exp Ther. 1988;247(3):1018–24.

    CAS  PubMed  Google Scholar 

  5. Lin AM, Freund RK, Hoffer BJ, Palmer MR. Ethanol-induced depressions of cerebellar Purkinje neurons are potentiated by beta-adrenergic mechanisms in rat brain. J Pharmacol Exp Ther. 1994;271(3):1175–80.

    CAS  PubMed  Google Scholar 

  6. Freund RK, Palmer MR. Beta adrenergic sensitization of gamma-aminobutyric acid receptors to ethanol involves a cyclic AMP/protein kinase A second-messenger mechanism. J Pharmacol Exp Ther. 1997;280(3):1192–200.

    CAS  PubMed  Google Scholar 

  7. Yang X, Knapp DJ, Criswell HE, Breese GR. Action of ethanol and zolpidem on gamma-aminobutyric acid responses from cerebellar Purkinje neurons: relationship to beta-adrenergic receptor input. Alcohol Clin Exp Res. 1998;22(8):1655–61.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Sapp DW, Yeh HH. Ethanol-GABAA receptor interactions: a comparison between cell lines and cerebellar Purkinje cells. J Pharmacol Exp Ther. 1998;284(2):768–76.

    CAS  PubMed  Google Scholar 

  9. Criswell HE, Ming Z, Griffith BL, Breese GR. Comparison of effect of ethanol on N-methyl-D-aspartate- and GABA-gated currents from acutely dissociated neurons: absence of regional differences in sensitivity to ethanol. J Pharmacol Exp Ther. 2003;304(1):192–9.

    Article  CAS  PubMed  Google Scholar 

  10. Criswell HE, Ming Z, Kelm MK, Breese GR. Brain regional differences in the effect of ethanol on GABA release from presynaptic terminals. J Pharmacol Exp Ther. 2008;326(2):596–603 [In Vitro].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Breese GR, Criswell HE, Carta M, Dodson PD, Hanchar HJ, Khisti RT, et al. Basis of the gabamimetic profile of ethanol. Alcohol Clin Exp Res. 2006;30(4):731–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Criswell HE, Breese GR. A conceptualization of integrated actions of ethanol contributing to its GABAmimetic profile: a commentary. Neuropsychopharmacology. 2005;30(8):1407–25 [Review].

    Article  CAS  PubMed  Google Scholar 

  13. Weiner JL, Valenzuela CF. Ethanol modulation of GABAergic transmission: the view from the slice. Pharmacol Ther. 2006;111(3):533–54.

    Article  CAS  PubMed  Google Scholar 

  14. Siggins GR, Roberto M, Nie Z. The tipsy terminal: presynaptic effects of ethanol. Pharmacol Ther. 2005;107(1):80–98.

    Article  CAS  PubMed  Google Scholar 

  15. Ming Z, Criswell HE, Yu G, Breese GR. Competing presynaptic and postsynaptic effects of ethanol on cerebellar purkinje neurons. Alcohol Clin Exp Res. 2006;30(8):1400–7.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Kelm MK, Criswell HE, Breese GR. Calcium release from presynaptic internal stores is required for ethanol to increase spontaneous gamma-aminobutyric acid release onto cerebellum Purkinje neurons. J Pharmacol Exp Ther. 2007;323(1):356–64.

    Article  CAS  PubMed  Google Scholar 

  17. Kelm MK, Criswell HE, Breese GR. The role of protein kinase A in the ethanol-induced increase in spontaneous GABA release onto cerebellar Purkinje neurons. J Neurophysiol. 2008;100(6):3417–28 [In Vitro Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Kelm MK, Weinberg RJ, Criswell HE, Breese GR. The PLC/IP 3 R/PKC pathway is required for ethanol-enhanced GABA release. Neuropharmacology. 2010;58(7):1179–86 [In Vitro Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Kelm MK, Criswell HE, Breese GR. Ethanol-enhanced GABA release: a focus on G protein-coupled receptors. Brain Res Rev. 2011;65(2):113–23 [Review].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Hirono M, Yamada M, Obata K. Ethanol enhances both action potential-dependent and action potential-independent GABAergic transmission onto cerebellar Purkinje cells. Neuropharmacology. 2009;57(2):109–20 [In Vitro Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  21. Mameli M, Botta P, Zamudio PA, Zucca S, Valenzuela CF. Ethanol decreases Purkinje neuron excitability by increasing GABA release in rat cerebellar slices. J Pharmacol Exp Ther. 2008;327(3):910–7 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Briatore F, Patrizi A, Viltono L, Sassoe-Pognetto M, Wulff P. Quantitative organization of GABAergic synapses in the molecular layer of the mouse cerebellar cortex. PLoS One. 2010;5(8):e12119 [Research Support, Non-U.S. Gov’t].

    Article  PubMed Central  PubMed  Google Scholar 

  23. Wadleigh A, Valenzuela CF. Ethanol increases GABAergic transmission and excitability in cerebellar molecular layer interneurons from GAD67-GFP knock-in mice. Alcohol Alcohol. 2012;47(1):1–8 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Middleton SJ, Racca C, Cunningham MO, Traub RD, Monyer H, Knopfel T, et al. High-frequency network oscillations in cerebellar cortex. Neuron. 2008;58(5):763–74 [In Vitro Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  25. Brickley SG, Mody I. Extrasynaptic GABA(A) receptors: their function in the CNS and implications for disease. Neuron. 2012;73(1):23–34 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Lee S, Yoon BE, Berglund K, Oh SJ, Park H, Shin HS, et al. Channel-mediated tonic GABA release from glia. Science. 2010;330(6005):790–6 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  27. Yoon BE, Woo J, Chun YE, Chun H, Jo S, Bae JY, et al. Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. J Physiol. 2014;592(Pt 22):4951–68.

    Article  CAS  PubMed  Google Scholar 

  28. Diaz MR, Wadleigh A, Hughes BA, Woodward JJ, Valenzuela CF. Bestrophin1 channels are insensitive to ethanol and do not mediate tonic GABAergic currents in cerebellar granule cells. Front Neurosci. 2011;5:148.

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Carta M, Mameli M, Valenzuela CF. Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability. J Neurosci. 2004;24(15):3746–51.

    Article  CAS  PubMed  Google Scholar 

  30. Hanchar HJ, Dodson PD, Olsen RW, Otis TS, Wallner M. Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity. Nat Neurosci. 2005;8(3):339–45.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Kaplan JS, Mohr C, Rossi DJ. Opposite actions of alcohol on tonic GABA(A) receptor currents mediated by nNOS and PKC activity. Nat Neurosci. 2013;16(12):1783–93 [In Vitro Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Santhakumar V, Meera P, Karakossian MH, Otis TS. A reinforcing circuit action of extrasynaptic GABAA receptor modulators on cerebellar granule cell inhibition. PLoS One. 2013;8(8):e72976 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Diaz MR, Wadleigh A, Kumar S, De Schutter E, Valenzuela CF. Na+/K + −ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells. PLoS One. 2013;8(1):e55673 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Mohr C, Kolotushkina O, Kaplan JS, Welsh J, Daunais JB, Grant KA, et al. Primate cerebellar granule cells exhibit a tonic GABAAR conductance that is not affected by alcohol: a possible cellular substrate of the low level of response phenotype. Front Neural Circ. 2013;7:189 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Google Scholar 

  35. Poltl A, Hauer B, Fuchs K, Tretter V, Sieghart W. Subunit composition and quantitative importance of GABAA receptor subtypes in the cerebellum of mouse and rat. J Neurochem. 2003;87(6):1444–55.

    Article  PubMed  Google Scholar 

  36. Wallner M, Hanchar HJ, Olsen RW. Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc Natl Acad Sci U S A. 2003;100(25):15218–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Hanchar HJ, Chutsrinopkun P, Meera P, Supavilai P, Sieghart W, Wallner M, et al. Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors. Proc Natl Acad Sci U S A. 2006;103(22):8546–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Wallner M, Hanchar HJ, Olsen RW. Alcohol selectivity of beta3-containing GABAA receptors: evidence for a unique extracellular alcohol/imidazobenzodiazepine Ro15-4513 binding site at the alpha+beta- subunit interface in alphabeta3delta GABAA receptors. Neurochem Res. 2014;39(6):1118–26 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Borghese CM, Harris RA. Studies of ethanol actions on recombinant delta-containing gamma-aminobutyric acid type A receptors yield contradictory results. Alcohol. 2007.

  40. Yamashita M, Marszalec W, Yeh JZ, Narahashi T. Effects of ethanol on tonic GABA currents in cerebellar granule cells and mammalian cells recombinantly expressing GABA(A) receptors. J Pharmacol Exp Ther. 2006;319(1):431–8.

    Article  CAS  PubMed  Google Scholar 

  41. Baur R, Kaur KH, Sigel E. Structure of alpha6 beta3 delta GABA(A) receptors and their lack of ethanol sensitivity. J Neurochem. 2009;111(5):1172–81 [Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  42. Meera P, Olsen RW, Otis TS, Wallner M. Alcohol- and alcohol antagonist-sensitive human GABAA receptors: tracking delta subunit incorporation into functional receptors. Mol Pharmacol. 2010;78(5):918–24 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Linden AM, Schmitt U, Leppa E, Wulff P, Wisden W, Luddens H, et al. Ro 15–4513 Antagonizes alcohol-induced sedation in mice through alphabetagamma2-type GABA(A) receptors. Front Neurosci. 2011;5:3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Stell BM, Rostaing P, Triller A, Marty A. Activation of presynaptic GABA(A) receptors induces glutamate release from parallel fiber synapses. J Neurosci. 2007;27(34):9022–31 [In Vitro Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  45. Dellal SS, Luo R, Otis TS. GABAA receptors increase excitability and conduction velocity of cerebellar parallel fiber axons. J Neurophysiol. 2012;107(11):2958–70 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Schmid G, Bonanno G, Raiteri L, Sarviharju M, Korpi ER, Raiteri M. Enhanced benzodiazepine and ethanol actions on cerebellar GABA(A) receptors mediating glutamate release in an alcohol-sensitive rat line. Neuropharmacology. 1999;38(9):1273–9.

    Article  CAS  PubMed  Google Scholar 

  47. Botta P, Mameli M, Floyd K, Radcliffe RA, Valenzuela CF. Ethanol sensitivity of GABAergic currents in cerebellar granule neurons is not increased by a single amino acid change (R100Q) in the {alpha}6 GABAA receptor subunit. J Pharmacol Exp Ther. 2007;17.

  48. Valenzuela CF, Mameli M, Carta M. Single-amino-acid difference in the sequence of alpha6 subunit dramatically increases the ethanol sensitivity of recombinant GABAA receptors. Alcohol Clin Exp Res. 2005;29(7):1356–7 [Letter].

    Article  PubMed  Google Scholar 

  49. Freund RK, Wang Y, Palmer MR. Differential effects of ethanol on the firing rates of Golgi-like neurons and Purkinje neurons in cerebellar slices in vitro. Neurosci Lett. 1993;164(1–2):9–12.

    Article  CAS  PubMed  Google Scholar 

  50. Botta P, de Souza FM, Sangrey T, De Schutter E, Valenzuela CF. Alcohol excites cerebellar Golgi cells by inhibiting the Na+/K+ ATPase. Neuropsychopharmacology. 2010;35(9):1984–96 [In Vitro Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Botta P, de Souza FM S, Sangrey T, De Schutter E, Valenzuela CF. Excitation of rat cerebellar Golgi cells by ethanol: further characterization of the mechanism. Alcohol Clin Exp Res. 2012;36(4):616–24 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Huang JJ, Yen CT, Tsai ML, Valenzuela CF, Huang C. Acute ethanol exposure increases firing and induces oscillations in cerebellar Golgi cells of freely moving rats. Alcohol Clin Exp Res. 2012;36(12):2110–6 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. White CN, Hamilton EJ, Garcia A, Wang D, Chia KK, Figtree GA, et al. Opposing effects of coupled and uncoupled NOS activity on the Na+−K+ pump in cardiac myocytes. Am J Physiol Cell Physiol. 2008;294(2):C572–8 [Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  54. Salapatek AM, Wang YF, Mao YK, Mori M, Daniel EE. Myogenic NOS in canine lower esophageal sphincter: enzyme activation, substrate recycling, and product actions. Am J Physiol. 1998;274(4 Pt 1):C1145–57 [Research Support, Non-U.S. Gov’t].

    CAS  PubMed  Google Scholar 

  55. Brickley SG, Cull-Candy SG, Farrant M. Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol. 1996;497(Pt 3):753–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Wall MJ, Usowicz MM. Development of action potential-dependent and independent spontaneous GABAA receptor-mediated currents in granule cells of postnatal rat cerebellum. Eur J Neurosci. 1997;9(3):533–48.

    Article  CAS  PubMed  Google Scholar 

  57. Bright DP, Renzi M, Bartram J, McGee TP, MacKenzie G, Hosie AM, et al. Profound desensitization by ambient GABA limits activation of delta-containing GABAA receptors during spillover. J Neurosci. 2011;31(2):753–63 [In Vitro Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Huang CM, Huang RH. Ethanol inhibits the sensory responses of cerebellar granule cells in anesthetized cats. Alcohol Clin Exp Res. 2007;31(2):336–44.

    Article  CAS  PubMed  Google Scholar 

  59. Wu G, Liu H, Jin J, Hong L, Lan Y, Chu CP, et al. Ethanol attenuates sensory stimulus-evoked responses in cerebellar granule cells via activation of GABA(A) receptors in vivo in mice. Neurosci Lett. 2014;561:107–11 [Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

  60. Choi DS, Wei W, Deitchman JK, Kharazia VN, Lesscher HM, McMahon T, et al. Protein kinase Cdelta regulates ethanol intoxication and enhancement of GABA-stimulated tonic current. J Neurosci. 2008;28(46):11890–9 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Offenhauser N, Castelletti D, Mapelli L, Soppo BE, Regondi MC, Rossi P, et al. Increased ethanol resistance and consumption in Eps8 knockout mice correlates with altered actin dynamics. Cell. 2006;127(1):213–26.

    Article  CAS  PubMed  Google Scholar 

  62. Carta M, Mameli M, Valenzuela CF. Alcohol potently modulates climbing fiber-->Purkinje neuron synapses: role of metabotropic glutamate receptors. J Neurosci. 2006;26(7):1906–12.

    Article  CAS  PubMed  Google Scholar 

  63. Belmeguenai A, Botta P, Weber JT, Carta M, De Ruiter M, De Zeeuw CI, et al. Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse. J Neurophysiol. 2008;100(6):3167–74 [In Vitro Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Su LD, Sun CL, Shen Y. Ethanol acutely modulates mGluR1-dependent long-term depression in cerebellum. Alcohol Clin Exp Res. 2010;34(7):1140–5 [Comparative Study Research Support, Non-U.S. Gov’t].

    CAS  PubMed  Google Scholar 

  65. He Q, Titley H, Grasselli G, Piochon C, Hansel C. Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD. J Neurophysiol. 2013;109(5):1333–42 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Botta P, Zucca A, Valenzuela CF. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input. Front Integr Neurosci. 2014;8:10.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Dar MS. Involvement of kappa-opioids in the mouse cerebellar adenosinergic modulation of ethanol-induced motor incoordination. Alcohol Clin Exp Res. 1998;22(2):444–54.

    Article  CAS  PubMed  Google Scholar 

  68. Dar MS. Mouse cerebellar adenosine-glutamate interactions and modulation of ethanol-induced motor incoordination. Alcohol Clin Exp Res. 2002;26(9):1395–403 [Comparative Study].

    Article  CAS  PubMed  Google Scholar 

  69. Taslim N, Soderstrom K, Dar MS. Role of mouse cerebellar nicotinic acetylcholine receptor (nAChR) alpha(4)beta(2)- and alpha(7) subtypes in the behavioral cross-tolerance between nicotine and ethanol-induced ataxia. Behav Brain Res. 2011;217(2):282–92.

    Article  CAS  PubMed  Google Scholar 

  70. Morrow AL, Herbert JS, Montpied P. Differential effects of chronic ethanol administration on GABA(A) receptor alpha1 and alpha6 subunit mRNA levels in rat cerebellum. Mol Cell Neurosci. 1992;3(3):251–8.

    Article  CAS  PubMed  Google Scholar 

  71. Mhatre MC, Ticku MK. Chronic ethanol administration alters gamma-aminobutyric acidA receptor gene expression. Mol Pharmacol. 1992;42(3):415–22.

    CAS  PubMed  Google Scholar 

  72. Vekovischeva OY, Uusi-Oukari M, Korpi ER. Chronic ethanol treatment and GABA(A) receptor alpha6 subunit gene expression: a study using alpha6 subunit-deficient mice. Addict Biol. 2000;5(4):463–7.

    Article  CAS  PubMed  Google Scholar 

  73. Sanna A, Congeddu E, Saba L, Porcella A, Marchese G, Ruiu S, et al. The cerebellar GABAA alpha6 subunit is differentially modulated by chronic ethanol exposure in normal (R100R) and mutated (Q100Q) sNP rats. Brain Res. 2004;998(2):148–54.

    Article  CAS  PubMed  Google Scholar 

  74. Marutha Ravindran CR, Mehta AK, Ticku MK. Effect of chronic administration of ethanol on the regulation of the delta-subunit of GABA(A) receptors in the rat brain. Brain Res. 2007;1174:47–52 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Diaz MR, Vollmer CC, Zamudio-Bulcock PA, Vollmer W, Blomquist SL, Morton RA, et al. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor delta subunit in cerebellar granule neurons and delays motor development in rats. Neuropharmacology. 2014;79:262–74 [Research Support, N.I.H., Extramural].

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Fein G, Greenstein D. Gait and balance deficits in chronic alcoholics: no improvement from 10 weeks through 1 year abstinence. Alcohol Clin Exp Res. 2013;37(1):86–95 [Research Support, N.I.H., Extramural].

    Article  PubMed Central  PubMed  Google Scholar 

  77. Zahr NM, Pitel AL, Chanraud S, Sullivan EV. Contributions of studies on alcohol use disorders to understanding cerebellar function. Neuropsychol Rev. 2010;20(3):280–9 [Research Support, N.I.H., Extramural Review].

    Article  PubMed Central  PubMed  Google Scholar 

  78. Lucas BR, Latimer J, Pinto RZ, Ferreira ML, Doney R, Lau M, et al. Gross motor deficits in children prenatally exposed to alcohol: a meta-analysis. Pediatrics. 2014;134(1):e192–209 [Review].

    Article  PubMed  Google Scholar 

  79. Riley EP, Infante MA, Warren KR. Fetal alcohol spectrum disorders: an overview. Neuropsychol Rev. 2011;21(2):73–80 [Research Support, N.I.H., Extramural Review].

    Article  PubMed Central  PubMed  Google Scholar 

  80. Jacobson SW, Jacobson JL, Stanton ME, Meintjes EM, Molteno CD. Biobehavioral markers of adverse effect in fetal alcohol spectrum disorders. Neuropsychol Rev. 2011;21(2):148–66 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  PubMed Central  PubMed  Google Scholar 

  81. Hsiao SH, Parrish AR, Nahm SS, Abbott LC, McCool BA, Frye GD. Effects of early postnatal ethanol intubation on GABAergic synaptic proteins. Brain Res Dev Brain Res. 2002;138(2):177–85 [Research Support, U.S. Gov’t, P.H.S.].

    Article  CAS  PubMed  Google Scholar 

  82. Hsiao SH, West JR, Mahoney JC, Frye GD. Postnatal ethanol exposure blunts upregulation of GABAA receptor currents in Purkinje neurons. Brain Res. 1999;832(1–2):124–35.

    Article  CAS  PubMed  Google Scholar 

  83. Karacay B, Li S, Bonthius DJ. Maturation-dependent alcohol resistance in the developing mouse: cerebellar neuronal loss and gene expression during alcohol-vulnerable and -resistant periods. Alcohol Clin Exp Res. 2008;32(8):1439–50 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Funding provided by NIH grant R01-AA014973 (CFV). We thank Dr. Don Partridge for critically reading the manuscript.

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  1. Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA

    C. Fernando Valenzuela & Karick Jotty

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Correspondence to C. Fernando Valenzuela.

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Valenzuela, C.F., Jotty, K. Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex—Recent Advances. Cerebellum 14, 438–446 (2015). https://doi.org/10.1007/s12311-014-0639-3

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