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

• Published in: Nature communications 2014-08, Vol.5 (1), p.4742-4742, Article 4742
• Main Authors: Isshiki, Masaaki, Tanaka, Shinji, Kuriu, Toshihiko, Tabuchi, Katsuhiko, Takumi, Toru, Okabe, Shigeo
• Format: Article
• Language: English
• Subjects: 14/69; 42/35; 631/378/1689/1373; 64/110; Animals; Autistic Disorder - etiology; Autistic Disorder - physiopathology; Biomarkers - analysis; Biomarkers - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Adhesion Molecules, Neuronal - genetics; Dendritic Spines - pathology; Dendritic Spines - physiology; Disease Models, Animal; Disks Large Homolog 4 Protein; Female; Green Fluorescent Proteins; Guanylate Kinases - metabolism; Humanities and Social Sciences; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; multidisciplinary; Nerve Tissue Proteins - genetics; Post-Synaptic Density; Pregnancy; Science; Science (multidisciplinary); Synapses - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5742

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. Impaired neuronal connectivity is implicated in autism spectrum disorder (ASD). In this study, the authors perform time-lapse imaging of brain neurons from different mouse models of ASD and provide evidence for enhanced turnover of excitatory synapses as a commonly occurring mechanism in ASD.