Role of the neuron-specific isoform of neurofibromin in learning impairment in a mouse model of neurofibromatosis 1

Abstract

Event Abstract Back to Event Role of the neuron-specific isoform of neurofibromin in learning impairment in a mouse model of neurofibromatosis 1 Y. Elgersma1, A. Omrani1* and G. Van Woerden1 1 Erasmus MC, Department of Neuroscience, Netherlands Neurofibromatosis type I (NF1) is an autosomal dominant disorder and is commonly associated with cognitive problems. Previous studies indicated that mice heterozygous for a null mutation in NF1 show impairment of visual-spatial learning and long-term potentiation (LTP) in the hippocampus that arises from increased activity of Ras pathway in interneurons. Although NF1 is expressed in all cells of the central nervous system, expression of NF1 containing alternatively spliced exon 9a is restricted to neurons. The existence of an evolutionary conserved neuron-specific isoform of neurofibromin raises the possibility that this isoform has unique properties by virtue of the presence of exon 9a and that this exon may have an important role on neurofibromin function in neurons. However, the functional significance of this neuron-specific NF1 isoform is unknown. To study the role of exon 9a in function of neurofibromin in neurons, we generated mice lacking the NF1-exone 9a isoform. Interestingly, our data show that mice lacking NF1-exon 9a have spatial learning and LTP deficits that arise from an increase in GABA-mediated inhibition in the hippocampus. In addition, we show that enhanced-GABA release in our mutants is caused by overactive ERK signaling in hippocampal interneurons. These data indicate that exon 9a is indeed critical for neurofibromin function in neurons. It is likely that this exon has a modulatory effect on Ras-GAP activity of neurofibromin in neurons. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Elgersma Y, Omrani A and Van Woerden G (2010). Role of the neuron-specific isoform of neurofibromin in learning impairment in a mouse model of neurofibromatosis 1. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00017 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: 24 Jun 2010; Published Online: 24 Jun 2010. * Correspondence: A. Omrani, Erasmus MC, Department of Neuroscience, Rotterdam, Netherlands, a.omrani@erasmusmc.nl 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 Y. Elgersma A. Omrani G. Van Woerden Google Y. Elgersma A. Omrani G. Van Woerden Google Scholar Y. Elgersma A. Omrani G. Van Woerden PubMed Y. Elgersma A. Omrani G. Van Woerden 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.