SALM4 negatively regulates NMDA receptor function and fear memory consolidation
DC Field | Value | Language |
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dc.contributor.author | Lie, Eunkyung | - |
dc.contributor.author | Yeo, Yeji | - |
dc.contributor.author | Lee, Eun-Jae | - |
dc.contributor.author | Shin, Wangyong | - |
dc.contributor.author | Kim, Kyungdeok | - |
dc.contributor.author | Han, Kyung Ah | - |
dc.contributor.author | Yang, Esther | - |
dc.contributor.author | Choi, Tae-Yong | - |
dc.contributor.author | Bae, Mihyun | - |
dc.contributor.author | Lee, Suho | - |
dc.contributor.author | Um, Seung Min | - |
dc.contributor.author | Choi, Se-Young | - |
dc.contributor.author | Kim, Hyun | - |
dc.contributor.author | Ko, Jaewon | - |
dc.contributor.author | Kim, Eunjoon | - |
dc.date.accessioned | 2022-02-19T01:40:37Z | - |
dc.date.available | 2022-02-19T01:40:37Z | - |
dc.date.created | 2022-02-08 | - |
dc.date.issued | 2021-09-29 | - |
dc.identifier.issn | 2399-3642 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/136294 | - |
dc.description.abstract | To elucidate the role of synaptic cell adhesion-like molecule 4 (SALM4) in altering synaptic function in the context of fear memory, Lie at al performed behavioural and electrophysiological assessments of SALM4 knockout mice undergoing cued fear, spatial, and object-recognition memory tasks. They demonstrated that SALM4 suppresses heightened GluN2B-expressing NMDA receptor function specifically during fear memory consolidation. Many synaptic adhesion molecules positively regulate synapse development and function, but relatively little is known about negative regulation. SALM4/Lrfn3 (synaptic adhesion-like molecule 4/leucine rich repeat and fibronectin type III domain containing 3) inhibits synapse development by suppressing other SALM family proteins, but whether SALM4 also inhibits synaptic function and specific behaviors remains unclear. Here we show that SALM4-knockout (Lrfn3(-/-)) male mice display enhanced contextual fear memory consolidation (7-day post-training) but not acquisition or 1-day retention, and exhibit normal cued fear, spatial, and object-recognition memory. The Lrfn3(-/-) hippocampus show increased currents of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors (GluN2B-NMDARs), but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors (AMPARs), which requires the presynaptic receptor tyrosine phosphatase PTP sigma. Chronic treatment of Lrfn3(-/-) mice with fluoxetine, a selective serotonin reuptake inhibitor used to treat excessive fear memory that directly inhibits GluN2B-NMDARs, normalizes NMDAR function and contextual fear memory consolidation in Lrfn3(-/-) mice, although the GluN2B-specific NMDAR antagonist ifenprodil was not sufficient to reverse the enhanced fear memory consolidation. These results suggest that SALM4 suppresses excessive GluN2B-NMDAR (not AMPAR) function and fear memory consolidation (not acquisition). | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PORTFOLIO | - |
dc.subject | ADHESION-LIKE MOLECULES | - |
dc.subject | LONG-TERM POTENTIATION | - |
dc.subject | PHOSPHORYLATION SITES | - |
dc.subject | SYNAPTIC PLASTICITY | - |
dc.subject | FAMILY | - |
dc.subject | FLUOXETINE | - |
dc.subject | EXPRESSION | - |
dc.subject | SUBUNIT | - |
dc.subject | NEUROLIGINS | - |
dc.subject | EXCITATION | - |
dc.title | SALM4 negatively regulates NMDA receptor function and fear memory consolidation | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Hyun | - |
dc.identifier.doi | 10.1038/s42003-021-02656-3 | - |
dc.identifier.scopusid | 2-s2.0-85116320041 | - |
dc.identifier.wosid | 000701977100002 | - |
dc.identifier.bibliographicCitation | COMMUNICATIONS BIOLOGY, v.4, no.1 | - |
dc.relation.isPartOf | COMMUNICATIONS BIOLOGY | - |
dc.citation.title | COMMUNICATIONS BIOLOGY | - |
dc.citation.volume | 4 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | ADHESION-LIKE MOLECULES | - |
dc.subject.keywordPlus | EXCITATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | FAMILY | - |
dc.subject.keywordPlus | FLUOXETINE | - |
dc.subject.keywordPlus | LONG-TERM POTENTIATION | - |
dc.subject.keywordPlus | NEUROLIGINS | - |
dc.subject.keywordPlus | PHOSPHORYLATION SITES | - |
dc.subject.keywordPlus | SUBUNIT | - |
dc.subject.keywordPlus | SYNAPTIC PLASTICITY | - |
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