TY - JOUR T1 - Excessive formation and stabilization of dendritic spine clusters in the MECP2 duplication syndrome mouse model of autism JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0282-20.2020 SP - ENEURO.0282-20.2020 AU - Ryan Thomas Ash AU - Jiyoung Park AU - Bernhard Suter AU - Huda Yaya Zoghbi AU - Stelios Manolis Smirnakis Y1 - 2020/11/09 UR - http://www.eneuro.org/content/early/2020/11/09/ENEURO.0282-20.2020.abstract N2 - Autism-associated genetic mutations may perturb the balance between stability and plasticity of synaptic connections in the brain. Here we report an increase in the formation and stabilization of dendritic spines in the cerebral cortex of the mouse model of MECP2-duplication syndrome, a high-penetrance form of syndromic autism. Increased stabilization is mediated entirely by spines that form cooperatively in 10-micron clusters and is observable across multiple cortical areas both spontaneously and following motor training. Excessive stability of dendritic spine clusters could contribute to behavioral rigidity and other phenotypes in syndromic autism.Significance Statement The inflexible repetitive behaviors, "insistence on sameness," and at times exceptional learning abilities seen in autism imply a defect in the neural processes underlying learning and memory, potentially affecting the balance between stability and plasticity of synaptic connections in the brain. Here we report a pathological bias toward stability of newly formed dendritic spines in the MECP2-duplication mouse model of autism. Enhanced spine stability is mediated entirely by spines aggregating within 10 µm of each other, in clusters. Enhanced clustered spine stability is observable in multiple brain areas both at rest and during motor training. The results suggest that some phenotypes of autism could arise from abnormal consolidation of clustered synaptic connections. ER -