Distorted neurocomputation by a small number of extra-large spines in psychiatric disorders Article Swipe
Kisho Obi-Nagata
,
Norimitsu Suzuki
,
Ryuhei Miyake
,
Matthew L. MacDonald
,
Kenneth N. Fish
,
Katsuya Ozawa
,
Kenichiro Nagahama
,
Tsukasa Okimura
,
Shoji Tanaka
,
Masanobu Kano
,
Yugo Fukazawa
,
Robert A. Sweet
,
Akiko Hayashi‐Takagi
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.ade5973
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.ade5973
Human genetics strongly support the involvement of synaptopathy in psychiatric disorders. However, trans-scale causality linking synapse pathology to behavioral changes is lacking. To address this question, we examined the effects of synaptic inputs on dendrites, cells, and behaviors of mice with knockdown of SETD1A and DISC1, which are validated animal models of schizophrenia. Both models exhibited an overrepresentation of extra-large (XL) synapses, which evoked supralinear dendritic and somatic integration, resulting in increased neuronal firing. The probability of XL spines correlated negatively with working memory, and the optical prevention of XL spine generation restored working memory impairment. Furthermore, XL synapses were more abundant in the postmortem brains of patients with schizophrenia than in those of matched controls. Our findings suggest that working memory performance, a pivotal aspect of psychiatric symptoms, is shaped by distorted dendritic and somatic integration via XL spines.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciadv.ade5973
- https://www.science.org/doi/pdf/10.1126/sciadv.ade5973?download=true
- OA Status
- gold
- Cited By
- 18
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4379983780
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4379983780Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1126/sciadv.ade5973Digital Object Identifier
- Title
-
Distorted neurocomputation by a small number of extra-large spines in psychiatric disordersWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-06-09Full publication date if available
- Authors
-
Kisho Obi-Nagata, Norimitsu Suzuki, Ryuhei Miyake, Matthew L. MacDonald, Kenneth N. Fish, Katsuya Ozawa, Kenichiro Nagahama, Tsukasa Okimura, Shoji Tanaka, Masanobu Kano, Yugo Fukazawa, Robert A. Sweet, Akiko Hayashi‐TakagiList of authors in order
- Landing page
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https://doi.org/10.1126/sciadv.ade5973Publisher landing page
- PDF URL
-
https://www.science.org/doi/pdf/10.1126/sciadv.ade5973?download=trueDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.science.org/doi/pdf/10.1126/sciadv.ade5973?download=trueDirect OA link when available
- Concepts
-
Dendritic spine, Schizophrenia (object-oriented programming), Neuroscience, Synapse, DISC1, Working memory, Psychology, Biology, Psychiatry, Hippocampal formation, Cognition, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
18Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 12, 2024: 2, 2023: 4Per-year citation counts (last 5 years)
- References (count)
-
58Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.effects | 29 |
| abstract_inverted_index.firing. | 73 |
| abstract_inverted_index.linking | 14 |
| abstract_inverted_index.matched | 114 |
| abstract_inverted_index.memory, | 83 |
| abstract_inverted_index.optical | 86 |
| abstract_inverted_index.pivotal | 124 |
| abstract_inverted_index.somatic | 67, 135 |
| abstract_inverted_index.spines. | 139 |
| abstract_inverted_index.suggest | 118 |
| abstract_inverted_index.support | 3 |
| abstract_inverted_index.synapse | 15 |
| abstract_inverted_index.working | 82, 93, 120 |
| abstract_inverted_index.However, | 11 |
| abstract_inverted_index.abundant | 101 |
| abstract_inverted_index.examined | 27 |
| abstract_inverted_index.findings | 117 |
| abstract_inverted_index.genetics | 1 |
| abstract_inverted_index.lacking. | 21 |
| abstract_inverted_index.neuronal | 72 |
| abstract_inverted_index.patients | 107 |
| abstract_inverted_index.restored | 92 |
| abstract_inverted_index.strongly | 2 |
| abstract_inverted_index.synapses | 98 |
| abstract_inverted_index.synaptic | 31 |
| abstract_inverted_index.behaviors | 37 |
| abstract_inverted_index.causality | 13 |
| abstract_inverted_index.controls. | 115 |
| abstract_inverted_index.dendritic | 65, 133 |
| abstract_inverted_index.distorted | 132 |
| abstract_inverted_index.exhibited | 55 |
| abstract_inverted_index.increased | 71 |
| abstract_inverted_index.knockdown | 41 |
| abstract_inverted_index.pathology | 16 |
| abstract_inverted_index.question, | 25 |
| abstract_inverted_index.resulting | 69 |
| abstract_inverted_index.symptoms, | 128 |
| abstract_inverted_index.synapses, | 61 |
| abstract_inverted_index.validated | 48 |
| abstract_inverted_index.behavioral | 18 |
| abstract_inverted_index.correlated | 79 |
| abstract_inverted_index.dendrites, | 34 |
| abstract_inverted_index.disorders. | 10 |
| abstract_inverted_index.generation | 91 |
| abstract_inverted_index.negatively | 80 |
| abstract_inverted_index.postmortem | 104 |
| abstract_inverted_index.prevention | 87 |
| abstract_inverted_index.extra-large | 59 |
| abstract_inverted_index.impairment. | 95 |
| abstract_inverted_index.integration | 136 |
| abstract_inverted_index.involvement | 5 |
| abstract_inverted_index.probability | 75 |
| abstract_inverted_index.psychiatric | 9, 127 |
| abstract_inverted_index.supralinear | 64 |
| abstract_inverted_index.trans-scale | 12 |
| abstract_inverted_index.Furthermore, | 96 |
| abstract_inverted_index.integration, | 68 |
| abstract_inverted_index.performance, | 122 |
| abstract_inverted_index.synaptopathy | 7 |
| abstract_inverted_index.schizophrenia | 109 |
| abstract_inverted_index.schizophrenia. | 52 |
| abstract_inverted_index.overrepresentation | 57 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5011682384 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 13 |
| corresponding_institution_ids | https://openalex.org/I165735259, https://openalex.org/I2800939219 |
| citation_normalized_percentile.value | 0.9260192 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |