Altered prefrontal modulation in a transgenic mouse with a low anxiety phenotype

Abstract

Event Abstract Back to Event Altered prefrontal modulation in a transgenic mouse with a low anxiety phenotype Eliane Proulx1*, Edwin J. Young2, Lucy R. Osborne3 and Evelyn K. Lambe1 1 University of Toronto, Department of Physiology, Canada 2 University of Toronto, Institute of Medical Science, Canada 3 University of Toronto, Department of Medicine, Canada Williams syndrome is a neurodevelopmental disorder characterized by hypersociability, mild to moderate mental retardation, elfin facial features and cardiovascular complications. It is caused by a genetic deletion of approximately 25 genes on chromosome 7, including the general transcription factor GTF2IRD1. A Gtf2ird1 knockout (KO) mouse has been generated and described recently. In brief, it was found that these mice exhibit decreased anxiety, enhanced sociability and reduced aggression. While the genetics and behavioral phenotype of the Gtf2ird1 KO mice have been characterized, the neuromodulation of brain areas important in coping with anxiety have not yet been examined. Since high levels of serotonin 5-HT1A receptors in prefrontal cortex are inversely correlated with anxiety levels, we examined how layer V prefrontal neurons responded to serotonin in male Gtf2ird1 KO mice. In addition, we investigated another prefrontal modulator – the group I metabotropic glutamate receptors (mGluR1/5) – which has been shown to have the opposite relationship with anxiety levels. Given that Gtf2ird1 knockout mice exhibit a low anxiety phenotype, we hypothesized that 5-HT1A and mGluR1/5 receptor function in prefrontal brain slices would be altered in opposite directions. We performed whole cell recordings in layers V pyramidal cells in medial prefrontal cortex (PFC) of adult Gtf2ird1 knockout mice and their wildtype siblings. Peak currents in response to bath application of 5-HT (30 µM, 30s) or the mGluR1/5 agonist DHPG (30 µM, 15 s) were measured in voltage clamp. Serotonin elicited significantly larger outward currents in KO than in WT. In prefrontal slices from both KO and WT mice, these currents were completely blocked by the selective 5-HT1A antagonist WAY-100635 (30 nM, 10 min). The currents were resistant to action potential blockade with TTX (2 μM, 10 min), suggesting that they are mediated directly by 5-HT1A receptors on the recorded neurons. We next investigated the inward currents elicited by group I mGluR receptors in layer V pyramidal neurons by application of the selective agonist DHPG (30 μM, 15 s) in prefrontal slices from KO and wildtype mice. As hypothesized, these currents were significantly smaller in the KO than the WT mice. Preliminary data additionally suggest that prefrontal cortical network activity is impaired in Gtf2ird1 KO mice. We conclude that 5-HT1A mediated responses are enhanced and group I mGluR receptor mediated responses are impaired in Gtf2ird1 mutant mice. This study was funded by the Scottish Rite Charitable Foundation (EKL) and a CIHR Frederick Banting and Charles Best CGS Doctoral Award (EP). Conference: B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Proulx E, Young EJ, Osborne LR and Lambe EK (2009). Altered prefrontal modulation in a transgenic mouse with a low anxiety phenotype. Front. Neurosci. Conference Abstract: B.R.A.I.N. platform in Physiology poster day 2009. doi: 10.3389/conf.neuro.03.2009.17.040 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: 18 Dec 2009; Published Online: 18 Dec 2009. * Correspondence: Eliane Proulx, University of Toronto, Department of Physiology, Toronto, Canada, eliane.proulx@utoronto.ca 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 Eliane Proulx Edwin J Young Lucy R Osborne Evelyn K Lambe Google Eliane Proulx Edwin J Young Lucy R Osborne Evelyn K Lambe Google Scholar Eliane Proulx Edwin J Young Lucy R Osborne Evelyn K Lambe PubMed Eliane Proulx Edwin J Young Lucy R Osborne Evelyn K Lambe 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.