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

Author

Listed:
  • Masaaki Isshiki

    (Graduate School of Medicine, the University of Tokyo)

  • Shinji Tanaka

    (Graduate School of Medicine, the University of Tokyo)

  • Toshihiko Kuriu

    (Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University)

  • Katsuhiko Tabuchi

    (Shinshu University School of Medicine
    PRESTO, Japan Science and Technology Agency (JST))

  • Toru Takumi

    (RIKEN Brain Science Institute
    CREST, Japan Science and Technology Agency (JST))

  • Shigeo Okabe

    (Graduate School of Medicine, the University of Tokyo)

Abstract

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.

Suggested Citation

  • Masaaki Isshiki & Shinji Tanaka & Toshihiko Kuriu & Katsuhiko Tabuchi & Toru Takumi & Shigeo Okabe, 2014. "Enhanced synapse remodelling as a common phenotype in mouse models of autism," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5742
    DOI: 10.1038/ncomms5742
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    Cited by:

    1. Anna Rubinski & Noam E Ziv, 2015. "Remodeling and Tenacity of Inhibitory Synapses: Relationships with Network Activity and Neighboring Excitatory Synapses," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-29, November.
    2. Takeshi Kaizuka & Takehiro Suzuki & Noriyuki Kishi & Kota Tamada & Manfred W. Kilimann & Takehiko Ueyama & Masahiko Watanabe & Tomomi Shimogori & Hideyuki Okano & Naoshi Dohmae & Toru Takumi, 2024. "Remodeling of the postsynaptic proteome in male mice and marmosets during synapse development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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