Cited by 152Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchNeuroscience and Neuropharmacology Research

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

Open access
Isshiki, Masaaki, Tanaka, Shinji, Kuriu, Toshihiko, Tabuchi, Katsuhiko, Takumi, Toru, Okabe, Shigeo·2014·Nature Communications

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ncomms5742

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review