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

• Main Author: Ryan Thomas Ash
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2014-03-01
• Series: Frontiers in Systems Neuroscience
• Subjects: ras Proteins; autism; MeCP2; structural plasticity; motor learning; dendritic spine; MAPK
• Online Access: http://journal.frontiersin.org/Journal/10.3389/conf.fnsys.2014.05.00039/full

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. <br/> <br/>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. <br/>