Event Abstract Back to Event Critical periods, homeostasis and a role for MHC Class I molecules Carla J. Shatz1* 1 Stanford University, Bio-X, United States Connections in adult brain are highly precise, but they do not start out that way. Precision emerges during development as synaptic connections remodel, a process that requires neural activity (action potentials and synaptic transmission) and involves regression of some synapses and strengthening and stabilization of others. Neural activity also regulates neuronal genes. In an unbiased PCR-based differential screen, we made the completely unexpected discovery that MHC Class I genes are expressed in neurons and are upregulated by neural activity and visual experience (Corriveau et al, 1998; Goddard et al, 2007). To assess requirements for MHCI in the CNS, mutant mice that lack stable surface expression of all MHCI, or specific MHCI genes, were examined. Synapse regression in the developing visual system did not occur, and in adult hippocampus synaptic strengthening was greater than normal (Huh et al, 2000). These observations suggest that neuronal MHCI may normally function in synaptic plasticity. Receptors could interact with neuronal MHCI and carry out these activity-dependent synaptic processes. In a systematic search, mRNA for PirB, an innate immune receptor, was found highly expressed in neurons in many regions of mouse CNS. We generated mutant mice lacking PirB function and discovered that the extent of plasticity in visual cortex is increased (Syken et al., 2006), as is synaptic strengthening in the hippocampus. Thus, PirB, like MHCI, appears to function as a “brake” on synaptic plasticity in the CNS. Together, results imply that this family of molecules, thought previously to function only in the immune system, may also act at neuronal synapses to limit how much- or perhaps how quickly- synapse strength changes in response to new experience. These molecules may be crucial for controlling circuit excitability and stability in developing as well as adult brain, and changes in their function may contribute to developmental disorders such as Autism and Schizophrenia. Supported by NIH Grants EY02858, MH071666, and Mathers Charitable Foundation. Conference: EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010. Presentation Type: Oral Presentation Topic: Talks Citation: Shatz CJ (2010). Critical periods, homeostasis and a role for MHC Class I molecules. Conference Abstract: EMBO workshop: Gaba Signalling and Brain Networks . doi: 10.3389/conf.fnins.2010.15.00051 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: 25 Jun 2010; Published Online: 25 Jun 2010. * Correspondence: Carla J Shatz, Stanford University, Bio-X, Stanford, United States, cshatz@stanford.edu 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 Carla J Shatz Google Carla J Shatz Google Scholar Carla J Shatz PubMed Carla J Shatz 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.
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