Abstract
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-μm 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.
Highlights
It has been proposed that phenotypes of autism spectrum disorder arise from an abnormal imbalance between the stability and plasticity of synaptic connections in the brain (Ramocki and Zoghbi, 2008)
Increased dendritic spine turnover has been observed in several autism mouse models (Chow et al, 2009; Jiang et al, 2013; Isshiki et al, 2014; Gdalyahu et al, 2015), including the MECP2-duplication, neuroligin-3, 15q duplication, PTEN, and CNTNAP2 mice, suggesting they share a deficit in the balance between structural synaptic plasticity and stability
We found that ;33% more new spines are formed after 4 d in apical tufts of MECP2-duplication mouse L5 pyramidal neurons compared with littermate controls
Summary
It has been proposed that phenotypes of autism spectrum disorder arise from an abnormal imbalance between the stability and plasticity of synaptic connections in the brain (Ramocki and Zoghbi, 2008). Such an imbalance may potentially contribute to the rigid, restricted behavioral repertoire and insistence on sameness seen in Received June 29, 2020; accepted September 14, 2020; First published November 9, 2020. Rebalancing synaptic stability and plasticity could provide a therapeutic avenue to promote behavioral flexibility in patients. Methyl-CpG-binding protein 2 (MeCP2) is an X-linked transcriptional regulator that contributes to the maintenance of neural circuit homeostasis through the activity-
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