Stabilization of dendritic spine clusters and hyperactive Ras-MAPK signaling predict enhanced motor learning in an autistic savant mouse model

Abstract

Event Abstract Back to Event Stabilization of dendritic spine clusters and hyperactive Ras-MAPK signaling predict enhanced motor learning in an autistic savant mouse model Ryan T. Ash1*, Shelly A. Buffington1, Mauro Costa-Mattioli1, Huda Y. Zoghbi1 and Stelios M. Smirnakis1 1 Baylor College of Medicine, United States That both prominent behavioral inflexibility and exceptional learning abilities are seen occasionally in autistic patients is a mystery. We hypothesize that these altered patterns of learning and memory can arise from a pathological imbalance between the stability and plasticity of internal neural representations. We evaluated this hypothesis in the mouse model of MECP2 duplication syndrome, which demonstrates enhanced motor learning, stereotyped behaviors, and social avoidance. Learning-associated structural plasticity was measured in the motor cortex of MECP2 duplication mice by 2-photon imaging (Fig. 1A). An increased stabilization rate of learning-associated dendritic spines was observed in mutants, and this correlated with rotarod performance. Analysis of the spatial distribution of stabilized spines revealed that the mutant’s increased spine stabilization was due to a specific increase in the stability of spines jointly formed in ~9-micron clusters. Clustered spine stabilization but not isolated spine stabilization predicted enhanced motor performance in MECP2 duplication mice (Fig. 1B). Biochemical assays of Ras-MAPK and mTOR pathway activation demonstrated profound hyperphosphorylation of MAPK in the motor cortex of MECP2 duplication mice with motor training (Fig. 1C). Taken together these data suggest that a pathological bias towards hyperstability of learning-associated dendritic spine clusters driven by hyperactive Ras-MAPK signaling could contribute to neurobehavioral phenotypes in this form of syndromic autism. Figure 1 Keywords: autism, MeCP2, dendritic spine, structural plasticity, motor learning, ras Proteins, MAPK Conference: 4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014. Presentation Type: Oral presentation Topic: functional or structural plasticity and homeostasis Citation: Ash RT, Buffington SA, Costa-Mattioli M, Zoghbi HY and Smirnakis SM (2014). Stabilization of dendritic spine clusters and hyperactive Ras-MAPK signaling predict enhanced motor learning in an autistic savant mouse model. Front. Syst. Neurosci. Conference Abstract: 4th NAMASEN Training Workshop - Dendrites 2014. doi: 10.3389/conf.fnsys.2014.05.00039 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: 11 Apr 2014; Published Online: 12 Jun 2014. * Correspondence: Mr. Ryan T Ash, Baylor College of Medicine, Houston, United States, rash@cns.bcm.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 Ryan T Ash Shelly A Buffington Mauro Costa-Mattioli Huda Y Zoghbi Stelios M Smirnakis Google Ryan T Ash Shelly A Buffington Mauro Costa-Mattioli Huda Y Zoghbi Stelios M Smirnakis Google Scholar Ryan T Ash Shelly A Buffington Mauro Costa-Mattioli Huda Y Zoghbi Stelios M Smirnakis PubMed Ryan T Ash Shelly A Buffington Mauro Costa-Mattioli Huda Y Zoghbi Stelios M Smirnakis 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.