Increased tonic GABA(A) receptor mediated signaling in dentate gyrus of SSADH deficient mice

Abstract

Event Abstract Back to Event Increased tonic GABA(A) receptor mediated signaling in dentate gyrus of SSADH deficient mice Zita Dósa1*, Jose L. Nieto-Gonzalez1, Michael K. Gibson2 and Kimmo Jensen1 1 Aarhus University, Synaptic Physiology Laboratory, Department of Physiology and Biophysics, Denmark 2 Michigan Technological University, Department of Biological Sciences, United States Excessive γ-aminobutyric acid (GABA) during brain development may lead to structural and functional changes in the brain tissue. This is the case in succinic semialdehyde dehydrogenase (SSADH) deficiency, which is an inherited neurometabolic disorder of GABA catabolism. Since SSADH participates in the breakdown of GABA, this condition leads to elevated GABA levels, but also increased γ-hydroxybutyric acid (GHB) in the brain, which also activates GABA receptors. SSADH deficient patients display neuropsychiatric symptoms, ataxia, and epileptic seizures, and SSADH knock-out mice were recently engineered to model the human disorder. Aims: The purpose of this study was to determine how the SSADH gene dosage impacts single-neuron physiology, since this might offer insight into how SSADH regulates the extracellular GABA levels in physiological and pathophysiological situations. Methods: To investigate the activation of GABA(A) receptors in SSADH deficiency, we performed whole-cell patch-clamp recordings in SSADH wild-type, heterozygous, and knock-out mice. Results: Both in dentate gyrus granule cells and interneurons, we found an increase in extrasynaptic GABA(A) receptor-mediated tonic current. On the other hand, the frequency and waveform of spontaneous inhibitory postsynaptic currents (sIPSCs) arising from GABAergic activity showed no significant alteration in these cells. Decreases in the SSADH gene dosage led to non-linear increases in GABA(A) receptor mediated neurotransmission in these mice. Conclusion: We conclude that SSADH deficiency preferentially leads to increased tonic GABAergic inhibition in the dentate gyrus, which may play a role for the pathophysiological activity in cortical networks. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cellular neuroscience Citation: Dósa Z, Nieto-Gonzalez JL, Gibson MK and Jensen K (2010). Increased tonic GABA(A) receptor mediated signaling in dentate gyrus of SSADH deficient mice. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00023 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Apr 2010; Published Online: 16 Apr 2010. * Correspondence: Zita Dósa, Aarhus University, Synaptic Physiology Laboratory, Department of Physiology and Biophysics, Aarhus, Denmark, zd@fi.au.dk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Zita Dósa Jose L Nieto-Gonzalez Michael K Gibson Kimmo Jensen Google Zita Dósa Jose L Nieto-Gonzalez Michael K Gibson Kimmo Jensen Google Scholar Zita Dósa Jose L Nieto-Gonzalez Michael K Gibson Kimmo Jensen PubMed Zita Dósa Jose L Nieto-Gonzalez Michael K Gibson Kimmo Jensen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.