title: Sensitivity of GABAergic Tonic Currents to Acute Ethanol in Cerebellar Granule Neurons is Not Age- or δ Subunit-Dependent in Developing Rats.
abstract: BACKGROUND
  The age of first exposure to ethanol (EtOH), as well as reduced sensitivity to its motor-impairing effects, are associated with a future predisposition to abuse EtOH. In adolescence, acute EtOH potentiates GABA transmission, including tonic inhibition mediated by δ-containing extrasynaptic GABAA receptors (GABAA Rs) in cerebellar granule neurons (CGNs), an effect that likely contributes to EtOH-induced motor impairment. Prenatal EtOH exposure is strikingly prevalent and is associated with increased EtOH abuse later in life; however, the acute effects of EtOH on GABA transmission in developing CGNs are unknown.
  
  
  METHODS
  Using whole-cell patch-clamp electrophysiological techniques in acute brain slices, we examined the acute effects of EtOH on GABA transmission and functionally assessed the role of δ-containing GABAA Rs in CGNs of preweanling (postnatal day [P] 12 to 14) and postweanling (P28 to 30) male Sprague-Dawley rats.
  
  
  RESULTS
  The magnitude of basal tonic currents were similar at both ages. However, 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride, an agonist with preferential affinity for δ-containing GABAA Rs, significantly potentiated tonic currents to a larger magnitude in CGNs from postweanlings compared to preweanlings. Conversely, acute application of EtOH (80 mM) significantly increased tonic currents and the frequency of spontaneous inhibitory postsynaptic currents to a similar extent in CGNs from pre- and postweanlings.
  
  
  CONCLUSIONS
  These findings highlight the sensitivity of the developing cerebellum to EtOH. Furthermore, this study demonstrates age-dependent functional changes in a well-characterized circuitry that may contribute to the short- and long-term effects of prenatal exposure to EtOH.
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, 1 University of New Mexico, Albuquerque, New Mexico.|Department of Psychology, Center for Development and Behavioral Neuroscience, Binghamton University-State University of New York, Binghamton, New York.
authors.forename: Marvin R
authors.initials: MR
authors.lastname: Diaz
authors.affiliation: Department of Neurosciences, University of New Mexico Health Sciences Center, 1 University of New Mexico, Albuquerque, New Mexico.
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
mesh_terms: D000367:Age Factors; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D058785:GABA-A Receptor Agonists; C000592156:Gabrd protein, rat; D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid
keywords: Cerebellum; Development; Ethanol; Prenatal; Tonic GABA