Cited by 93Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeural dynamics and brain function

Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function

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Berryer, Martin H., Chattopadhyaya, Bidisha, Xing, Paul, Riebe, Ilse, Bosoi, Ciprian, Sanon, Nathalie, Antoine-Bertrand, Judith, Lévesque, Maxime +7 more·2016·Nature Communications

Abstract

Haploinsufficiency of the SYNGAP1 gene, which codes for a Ras GTPase-activating protein, impairs cognition both in humans and in mice. Decrease of Syngap1 in mice has been previously shown to cause cognitive deficits at least in part by inducing alterations in glutamatergic neurotransmission and premature maturation of excitatory connections. Whether Syngap1 plays a role in the development of cortical GABAergic connectivity and function remains unclear. Here, we show that Syngap1 haploinsufficiency significantly reduces the formation of perisomatic innervations by parvalbumin-positive basket cells, a major population of GABAergic neurons, in a cell-autonomous manner. We further show that Syngap1 haploinsufficiency in GABAergic cells derived from the medial ganglionic eminence impairs their connectivity, reduces inhibitory synaptic activity and cortical gamma oscillation power, and causes cognitive deficits. Our results indicate that Syngap1 plays a critical role in GABAergic circuit function and further suggest that Syngap1 haploinsufficiency in GABAergic circuits may contribute to cognitive deficits.

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  • Syngap1 deficiency selectively in GABAergic neurons decreases presynaptic bouton density on the soma and reduces terminal axon branching on cortical interneurons.

    “Syngap1 deficiency selectively induced in GABAergic neurons results in decreased density of presynaptic boutons terminating on the soma as well as reduced terminal branching of axons on interneurons of the cortex [33].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [33]

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Authors
Berryer, M. H., Chattopadhyaya, B., Xing, P., Riebe, I., Bosoi, C., Sanon, N., Antoine-Bertrand, J., Lévesque, M., Avoli, M., Hamdan, F. F., Carmant, L., Lamarche-Vane, N., Lacaille, J.-C., Michaud, J. L., & Di Cristo, G.
Affiliations
  • CHU Sainte-Justine Research Center (CA)
  • Université de Montréal (CA)
  • Montreal Neurological Institute and Hospital (CA)
  • Centre Hospitalier Universitaire Sainte-Justine (CA)
Corresponding author
Michaud, Jacques L.
Venue
Nature Communications
Published
2016-11-09
Volume
7
Issue
1
Pages
13340-13340
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2553225945
Cited by
93
References
70
Citations by year
2026: 8 · 2025: 6 · 2024: 15 · 2023: 7 · 2022: 11 · 2021: 9 · 2020: 13 · 2019: 12 · 2018: 8 · 2017: 4
FWCI
4.49
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders
  • McGill University
  • Savoy Foundation
  • University of Edinburgh
  • Universität Zürich
  • Canadian Institutes of Health Research (130430, 10848, MOP-10848)
  • Natural Sciences and Engineering Research Council of Canada
  • Fonds de Recherche du Québec - Santé
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
SYNGAP1, haploinsufficiency, GABAergic neurons, basket cells, parvalbumin, inhibitory synapses, synaptic inhibition, medial ganglionic eminence, cognitive impairment, Ras GTPase-activating protein
MeSH terms
Animals, Cells, Cultured, Cognition, Cognition Disorders, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Synapses, ras GTPase-Activating Proteins, Mice, Gene Knockdown Techniques, Haploinsufficiency, GABAergic Neurons, Primary Cell Culture

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