Reduced inhibitory gate in the barrel cortex of Neuroligin3R451Cknock-in mice, an animal model of autism spectrum disorders
Open accessAbstract
Neuroligins are postsynaptic adhesion molecules that interacting with presynaptic neurexins ensure the cross-talk between pre- and postsynaptic specializations. Rare mutations in neurexin-neuroligin genes have been linked to autism spectrum disorders (ASDs). One of these, the R451C mutation of the gene encoding for Neuroligin3 (Nlgn3), has been found in patients with familial forms of ASDs. Animals carrying this mutation (NL3(R451C) knock-in mice) exhibit impaired social behaviors, reminiscent of those observed in ASD patients, associated with major alterations in both GABAergic and glutamatergic transmission, which vary among different brain regions and at different developmental stages. Here, pair recordings from parvalbumin- (PV) expressing basket cells and spiny neurons were used to study GABAergic synaptic signaling in layer IV barrel cortex of NL3(R451C) mutant mice. We found that the R451C mutation severely affects the probability of GABA release from PV-expressing basket cells, responsible for controlling via thalamo-cortical inputs the feed-forward inhibition. No changes in excitatory inputs to parvalbumin-positive basket cells or spiny neurons were detected. These data clearly show that primary targets of the NL3 mutation are PV-expressing basket cells, independently of the brain region where they are localized. Changes in the inhibitory gate of layer IV somatosensory cortex may alter sensory processing in ASD patients leading to misleading sensory representations with difficulties to combine pieces of information into a unified perceptual whole.
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Manipulations of other genes associated with intellectual disability and ASD (e.g., MECP2, NLGN3, Shank3, CNTNAP2) reveal diverse abnormalities within cortical GABAergic circuits.
“Manipulations of other genes associated with intellectual disability and ASD (for example, MECP2, NLGN3, Shank3; CNTNAP2) reveal diverse abnormalities within cortical GABAergic circuits.27, 28, 113, 114, 115”
From Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia (2017) · cites this paper as [113]
Both increase and decrease in the number of PV-IR cells are reported in these models.
“Both increase and decrease in number of PV-IR cells are reported.”
From Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia (2017) · cites this paper as [113]
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Self-citationStructural Insights into Protein Mutations Related to Autism Spectrum Disorders: A Systematic Review
Das, M. R., Rahman, M., & Zhou, C. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00526 · Cited by 3 · see citing works
Analyses of Human Genetic Data to Identify Clinically Relevant Domains of Neuroligins
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Enhanced cross-modal activation of sensory cortex in mouse models of autismPreprint
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Fxr1 Deletion from Cortical Parvalbumin Interneurons Modifies Their Excitatory Synaptic Responses
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Temporal Dynamics of Cortical Adaptation
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Contribution of the potassium / chloride cotransporter KCC2 to hippocampal rhythmopathy
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- Authors
- Cellot, G., & Cherubini, E.
- Affiliations
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- Corresponding author
- Cherubini, Enrico
- Venue
- Physiological Reports
- Publisher
- Wiley
- Published
- 2014-07
- Volume
- 2
- Issue
- 7
- Pages
- e12077
- ISSN
- 2051-817X (ISSN-L)
- PMC
- PMC4187543
- OpenAlex
- W2161723579
- Cited by
- 38
- References
- 67
- Citations by year
- 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 3 · 2014: 2
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Physiological Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- SDL (submittedVersion, other-oa)
- Funders
- Ministero dell'Istruzione, dell'Universita' e della Ricerca (PRIN 2011)
- Telethon (GGP11043)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- autism spectrum disorder, barrel cortex, parvalbumin basket cells, GABAergic inhibition, feedforward inhibition, thalamocortical input, somatosensory cortex, synaptic transmission, sensory processing
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.
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