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dc.contributor.authorMorel, Caroline
dc.contributor.authorSherrin, Tessi
dc.contributor.authorKennedy, Norman J.
dc.contributor.authorForest, Kelly H.
dc.contributor.authorBarutcu, Seda
dc.contributor.authorRobles, Michael
dc.contributor.authorCarpenter-Hyland, Ezekiel
dc.contributor.authorAlfulaij, Naghum
dc.contributor.authorStanden, Claire L.
dc.contributor.authorNichols, Robert A.
dc.contributor.authorBenveniste, Morris
dc.contributor.authorDavis, Roger J.
dc.contributor.authorTodorovic, Cedomir
dc.date2022-08-11T08:08:22.000
dc.date.accessioned2022-08-23T15:52:59Z
dc.date.available2022-08-23T15:52:59Z
dc.date.issued2018-04-11
dc.date.submitted2018-04-09
dc.identifier.citation<p>J Neurosci. 2018 Apr 11;38(15):3708-3728. doi: 10.1523/JNEUROSCI.1913-17.2018. Epub 2018 Mar 14. <a href="https://doi.org/10.1523/JNEUROSCI.1913-17.2018">Link to article on publisher's site</a></p>
dc.identifier.issn0270-6474 (Linking)
dc.identifier.doi10.1523/JNEUROSCI.1913-17.2018
dc.identifier.pmid29540552
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29261
dc.description.abstractThe c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDA receptor-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT: The results of this study demonstrate that JNK activation induced by the JIP1 scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study reports the identification of JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDA receptor-dependent synaptic plasticity and memory.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29540552&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2018 the authors. Publisher PDF posted after 6 months as allowed by the publisher's author rights policy at http://www.jneurosci.org/sites/default/files/files/JN_License_to_Publish.pdf.
dc.subjectJIP1
dc.subjectJNK
dc.subjectLTP
dc.subjectfear
dc.subjectmemory
dc.subjectplasticity
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectDevelopmental Biology
dc.subjectEnzymes and Coenzymes
dc.subjectMolecular and Cellular Neuroscience
dc.subjectMolecular Biology
dc.titleJIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory
dc.typeJournal Article
dc.source.journaltitleThe Journal of neuroscience : the official journal of the Society for Neuroscience
dc.source.volume38
dc.source.issue15
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2495&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1492
dc.legacy.embargo2018-10-11T00:00:00-07:00
dc.identifier.contextkey11928421
refterms.dateFOA2022-08-23T15:52:59Z
html.description.abstract<p>The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDA receptor-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT: The results of this study demonstrate that JNK activation induced by the JIP1 scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study reports the identification of JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDA receptor-dependent synaptic plasticity and memory.</p>
dc.identifier.submissionpathfaculty_pubs/1492
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.contributor.departmentDavis Lab
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages3708-3728


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