Sensitivity of GABAergic Tonic Currents to Acute Ethanol in Cerebellar Granule Neurons is Not Age‐ or δ Subunit‐Dependent in Developing Rats. (January 2016)

• Record Type: Journal Article
• Authors: Diaz, Marvin R.; Valenzuela, C. Fernando
• Is Part Of: Alcoholism. Volume 40:Number 1(2016)
• Page Start: 83
• Page End: 92
• Publication Date: 2016-01
• Subjects: Ethanol -- Cerebellum -- Tonic GABA -- Development -- Prenatal; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12940
• Languages: English
• ISSNs: 0145-6008

Abstract

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.