Enhanced synapse remodelling as a common phenotype in mouse models of autism
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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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Nlgn3 KI mice show greater postnatal turnover of excitatory spines in layer II and III pyramidal neurons in the anterior frontal cortex and increased vesicular GABA transporter expression without changes in inhibitory synapse number or ultrastructure in the somatosensory cortex.
“Synaptic changes in the Nlgn3 KI mice include greater postnatal turnover of excitatory spines in layer II and III pyramidal neurons in the anterior frontal cortex [172], and increased vesicular GABA transporter expression without changes in inhibitory synapse number or ultrastructure in neurons in the somatosensory cortex [345].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [172]
PatDp/+ mice, but not matDp/+ mice, show increased postnatal turnover of excitatory spines in the somatosensory and anterior frontal cortex.
“PatDp/+ mice, but not matDp/+ mice, show increased postnatal turnover of excitatory spines in the somatosensory and anterior frontal cortex [172].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [172]
BTBR mice have more serotonin-expressing neurons in the caudal portions of the median and dorsal raphe but decreased axon terminals in the hippocampal CA1, decreased adult neurogenesis in the dentate gyrus, upregulation of postnatal turnover of excitatory synapses in the anterior frontal cortex, and unaltered synaptic density and PSD thickness in the somatosensory cortex.
“The presence of more serotonin-expressing neurons in the caudal portions of the median and dorsal raphe but decreased axon terminals in the hippocampal CA1 [134], decreased adult neurogenesis in the dentate gyrus [338], upregulation of postnatal turnover of excitatory synapses in the anterior frontal cortex [172], and unaltered synaptic density and PSD thickness in the somatosensory cortex [381]”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [172]
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Self-citation
- Authors
- Isshiki, M., Tanaka, S., Kuriu, T., Tabuchi, K., Takumi, T., & Okabe, S.
- Affiliations
- The University of Tokyo (JP)
- Tokushima Bunri University (JP)
- Shinshu University (JP)
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Okabe, Shigeo
- Venue
- Nature Communications
- Published
- 2014-08-21
- Volume
- 5
- Issue
- 1
- Pages
- 4742-4742
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2039450535
- Cited by
- 152
- References
- 70
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 15 · 2023: 11 · 2022: 10 · 2021: 14 · 2020: 14 · 2019: 15 · 2018: 16 · 2017: 16 · 2016: 19 · 2015: 9 · 2014: 1
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (21220008, 25117006)
- Japan Society for the Promotion of Science (25242077, 25282242, 26250014, 25117006, 21220008)
- RIKEN
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, dendritic spines, PSD-95, gephyrin, excitatory synapses, inhibitory synapses, thalamocortical connections, neuroligin-3, neuronal connectivity, mouse model
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Autistic Disorder, Carrier Proteins, Disease Models, Animal, Female, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Mutant Strains, Nerve Tissue Proteins, Pregnancy, Synapses, Biomarkers, Cell Adhesion Molecules, Neuronal, Dendritic Spines, Green Fluorescent Proteins, Guanylate Kinases, Post-Synaptic Density
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