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Publication : Enhanced synapse remodelling as a common phenotype in mouse models of autism.

First Author  Isshiki M Year  2014
Journal  Nat Commun Volume  5
Pages  4742 PubMed ID  25144834
Mgi Jnum  J:274559 Mgi Id  MGI:6296514
Doi  10.1038/ncomms5742 Citation  Isshiki M, et al. (2014) Enhanced synapse remodelling as a common phenotype in mouse models of autism. Nat Commun 5:4742
abstractText  Developmental deficits in neuronal connectivity are considered to be present in patients with autism spectrum disorders (ASDs). Here we examine this possibility by using in vivo spine imaging in the early postnatal cortex of ASD mouse models. Spines are classified by the presence of either the excitatory postsynaptic marker PSD-95 or the inhibitory postsynaptic marker gephyrin. ASD mouse models show consistent upregulation in the dynamics of PSD-95-positive spines, which may subsequently contribute to stable synaptic connectivity. In contrast, spines receiving inputs from the thalamus, detected by the presence of gephyrin clusters, are larger, highly stable and unaffected in ASD mouse models. Importantly, two distinct mouse models, human 15q11-13 duplication and neuroligin-3 R451C point mutation, show highly similar phenotypes in spine dynamics. This selective impairment in dynamics of PSD-95-positive spines receiving intracortical projections may be a core component of early pathological changes and be a potential target of early intervention.
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