Abstract
MECP2-duplication syndrome is an X-linked form of syndromic autism caused by genomic duplication of the region encoding Methyl-CpG-binding protein 2. Mice overexpressing MECP2 demonstrate social impairment, behavioral inflexibility, and altered patterns of learning and memory. Previous work showed abnormally increased stability of dendritic spines formed during motor training in the apical tuft of primary motor cortex (area M1) corticospinal neurons in the MECP2-duplication mouse model. In the current study, we measure the structural plasticity of axonal boutons in Layer 5 (L5) pyramidal neuron projections to layer 1 of area M1 during motor training. In wild-type littermate control mice we find that during rotarod training, bouton formation rate changes minimally, if at all, while bouton elimination rate more than doubles. Notably, the observed upregulation in bouton elimination with training is absent in MECP2-duplication mice. This result provides further evidence of an imbalance between structural stability and plasticity in this form of syndromic autism. Furthermore, the observation that axonal bouton elimination more than doubles with motor training in wild-type animals contrasts with the increase of dendritic spine consolidation observed in corticospinal neurons at the same layer. This dissociation suggests that different area M1 microcircuits may manifest different patterns of structural synaptic plasticity during motor training.
Significance Statement Abnormal balance between synaptic stability and plasticity is a feature of several autism spectrum disorders, often corroborated by in vivo studies of dendritic spine turnover. Here we provide the first evidence that abnormally increased stability of axonal boutons, the presynaptic component of excitatory synapses, occurs during motor training in the MECP2 duplication syndrome mouse model of autism. In contrast, in normal controls, axonal bouton elimination in L5 pyramidal neuron projections to layer 1 of area M1 more than doubles with motor training. The fact that axonal projection boutons get eliminated, while corticospinal dendritic spines get consolidated with motor training in layer 1 of area M1, suggests that structural plasticity manifestations differ across different M1 microcircuits.
Footnotes
Authors report no conflict of interest.
R.T.A. received support from the Autism Speaks Weatherstone Fellowship and the BCM Medical Scientist Training Program. This work was supported by grants from the Simons Foundation and March of Dimes to S.M.S., the Howard Hughes Medical Institute and NINDS HD053862 to H.Y.Z., and the Baylor Intellectual and Developmental Disabilities Research Center (P30HD024064) Mouse Neurobehavioral Core.
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