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IQSEC3 Deletion Impairs Fear Memory Through Upregulation of Ribosomal S6K1 Signaling in the Hippocampus

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dc.contributor.authorKim D.-
dc.contributor.authorJung H.-
dc.contributor.authorShirai Y.-
dc.contributor.authorKim H.-
dc.contributor.authorKim J.-
dc.contributor.authorLim D.-
dc.contributor.authorMori T.-
dc.contributor.authorLee H.-
dc.contributor.authorPark D.-
dc.contributor.authorKim H.Y.-
dc.contributor.authorGuo Q.-
dc.contributor.authorPang B.-
dc.contributor.authorQiu W.-
dc.contributor.authorCao X.-
dc.contributor.authorKouyama-Suzuki E.-
dc.contributor.authorUemura T.-
dc.contributor.authorKasem E.-
dc.contributor.authorFu Y.-
dc.contributor.authorKim S.-
dc.contributor.authorTokunaga A.-
dc.contributor.authorYoshizawa T.-
dc.contributor.authorSuzuki T.-
dc.contributor.authorSakagami H.-
dc.contributor.authorLee K.J.-
dc.contributor.authorKo J.-
dc.contributor.authorTabuchi K.-
dc.contributor.authorUm J.W.-
dc.date.accessioned2023-08-16T09:30:16Z-
dc.date.available2023-08-16T09:30:16Z-
dc.date.created2022-05-31-
dc.date.issued2022-05-
dc.identifier.issn0006-3223-
dc.identifier.urihttp://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/234-
dc.description.abstractBackground: IQSEC3, a gephyrin-binding GABAergic (gamma-aminobutyric acidergic) synapse-specific guanine nucleotide exchange factor, was recently reported to regulate activity-dependent GABAergic synapse maturation, but the underlying signaling mechanisms remain incompletely understood. Methods: We generated mice with conditional knockout (cKO) of Iqsec3 to examine whether altered synaptic inhibition influences hippocampus-dependent fear memory formation. In addition, electrophysiological recordings, immunohistochemistry, and behavioral assays were used to address our question. Results: We found that Iqsec3-cKO induces a specific reduction in GABAergic synapse density, GABAergic synaptic transmission, and maintenance of long-term potentiation in the hippocampal CA1 region. In addition, Iqsec3-cKO mice exhibited impaired fear memory formation. Strikingly, Iqsec3-cKO caused abnormally enhanced activation of ribosomal P70-S6K1–mediated signaling in the hippocampus but not in the cortex. Furthermore, inhibiting upregulated S6K1 signaling by expressing dominant-negative S6K1 in the hippocampal CA1 of Iqsec3-cKO mice completely rescued impaired fear learning and inhibitory synapse density but not deficits in long-term potentiation maintenance. Finally, upregulated S6K1 signaling was rescued by IQSEC3 wild-type, but not by an ARF-GEF (adenosine diphosphate ribosylation factor–guanine nucleotide exchange factor) inactive IQSEC3 mutant. Conclusions: Our results suggest that IQSEC3-mediated balanced synaptic inhibition in hippocampal CA1 is critical for the proper formation of hippocampus-dependent fear memory.-
dc.language영어-
dc.language.isoen-
dc.publisherElsevier BV-
dc.titleIQSEC3 Deletion Impairs Fear Memory Through Upregulation of Ribosomal S6K1 Signaling in the Hippocampus-
dc.typeArticle-
dc.contributor.affiliatedAuthorLee K.J.-
dc.identifier.doi10.1016/j.biopsych.2021.12.016-
dc.identifier.scopusid2-s2.0-85125507356-
dc.identifier.wosid000798814400007-
dc.identifier.bibliographicCitationBiological Psychiatry, v.91, no.9, pp.821 - 831-
dc.relation.isPartOfBiological Psychiatry-
dc.citation.titleBiological Psychiatry-
dc.citation.volume91-
dc.citation.number9-
dc.citation.startPage821-
dc.citation.endPage831-
dc.type.rimsART-
dc.description.journalClass1-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaNeurosciences & Neurology-
dc.relation.journalResearchAreaPsychiatry-
dc.relation.journalWebOfScienceCategoryNeurosciences-
dc.relation.journalWebOfScienceCategoryPsychiatry-
dc.subject.keywordPlusNUCLEOTIDE EXCHANGE FACTOR-
dc.subject.keywordPlusNEURONAL CIRCUITS-
dc.subject.keywordPlusAMYGDALA-
dc.subject.keywordPlusMTOR-
dc.subject.keywordPlusKINASE-
dc.subject.keywordPlusRAPAMYCIN-
dc.subject.keywordPlusINHIBITION-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusPLASTICITY-
dc.subject.keywordPlusSYNARFGEF-
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