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dc.contributor.authorSherrin, Tessi
dc.contributor.authorBlank, Thomas
dc.contributor.authorHippel, Cathrin
dc.contributor.authorRayner, Martin
dc.contributor.authorDavis, Roger J.
dc.contributor.authorTodorovic, Cedomir
dc.date2022-08-11T08:08:16.000
dc.date.accessioned2022-08-23T15:48:50Z
dc.date.available2022-08-23T15:48:50Z
dc.date.issued2010-10-06
dc.date.submitted2016-02-29
dc.identifier.citationJ Neurosci. 2010 Oct 6;30(40):13348-61. doi: 10.1523/JNEUROSCI.3492-10.2010. <a href="http://dx.doi.org/10.1523/JNEUROSCI.3492-10.2010">Link to article on publisher's site</a>
dc.identifier.issn0270-6474 (Linking)
dc.identifier.doi10.1523/JNEUROSCI.3492-10.2010
dc.identifier.pmid20926661
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28297
dc.description.abstractIn the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatory cytokines, brain injury and ischemic insult, or exposure to psychological acute stressors induce activation of hippocampal JNKs. Here we report that exposure to acute stress caused activation of JNKs in the hippocampal CA1 and CA3 subfields, and impaired contextual fear conditioning. Conversely, intrahippocampal injection of JNKs inhibitors sp600125 (30 mum) or D-JNKI1 (8 mum) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 mug/mul), a potent JNKs activator, mimicked memory-impairing effects of stress on contextual fear. This anisomycin-induced amnesia was abolished after cotreatment with JNKs selective inhibitor sp600125 without affecting anisomycin's ability to effectively inhibit protein synthesis as measured by c-Fos immunoreactivity. We also demonstrated milder and transient activation of the JNKs pathway in the CA1 subfield of the hippocampus during contextual fear conditioning and an enhancement of contextual fear after pharmacological inhibition of JNKs under baseline conditions. Finally, using combined biochemical and transgenic approaches with mutant mice lacking different members of the JNK family (Jnk1, Jnk2, and Jnk3), we provided evidence that JNK2 and JNK3 are critically involved in stress-induced deficit of contextual fear, while JNK1 mainly regulates baseline learning in this behavioral task. Together, these results support the possibility that hippocampal JNKs serve as a critical molecular regulator in the formation of contextual fear.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20926661&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>Copyright of all material published in <em>The Journal of Neuroscience</em> remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a <a href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International (CC BY 4.0) license</a>.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAmino Acid Sequence
dc.subjectAmnesia
dc.subjectAnimals
dc.subjectAnisomycin
dc.subjectAssociation Learning
dc.subjectAvoidance Learning
dc.subjectCA1 Region, Hippocampal
dc.subjectCA3 Region, Hippocampal
dc.subjectDown-Regulation
dc.subjectFemale
dc.subjectHippocampus
dc.subjectIsoenzymes
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMitogen-Activated Protein Kinase 10
dc.subjectinhibitors
dc.subjectMitogen-Activated Protein Kinase 8
dc.subjectinhibitors
dc.subjectMitogen-Activated Protein Kinase 9
dc.subjectinhibitors
dc.subjectMolecular Sequence Data
dc.subjectNeurons
dc.subjectProtein Kinase Inhibitors
dc.subjectStress, Psychological
dc.subjectBehavioral Neurobiology
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular and Cellular Neuroscience
dc.subjectMolecular Biology
dc.titleHippocampal c-Jun-N-terminal kinases serve as negative regulators of associative learning
dc.typeJournal Article
dc.source.journaltitleThe Journal of neuroscience : the official journal of the Society for Neuroscience
dc.source.volume30
dc.source.issue40
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1026&amp;context=davis&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/davis/27
dc.identifier.contextkey8234480
refterms.dateFOA2022-08-23T15:48:51Z
html.description.abstract<p>In the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatory cytokines, brain injury and ischemic insult, or exposure to psychological acute stressors induce activation of hippocampal JNKs. Here we report that exposure to acute stress caused activation of JNKs in the hippocampal CA1 and CA3 subfields, and impaired contextual fear conditioning. Conversely, intrahippocampal injection of JNKs inhibitors sp600125 (30 mum) or D-JNKI1 (8 mum) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 mug/mul), a potent JNKs activator, mimicked memory-impairing effects of stress on contextual fear. This anisomycin-induced amnesia was abolished after cotreatment with JNKs selective inhibitor sp600125 without affecting anisomycin's ability to effectively inhibit protein synthesis as measured by c-Fos immunoreactivity. We also demonstrated milder and transient activation of the JNKs pathway in the CA1 subfield of the hippocampus during contextual fear conditioning and an enhancement of contextual fear after pharmacological inhibition of JNKs under baseline conditions. Finally, using combined biochemical and transgenic approaches with mutant mice lacking different members of the JNK family (Jnk1, Jnk2, and Jnk3), we provided evidence that JNK2 and JNK3 are critically involved in stress-induced deficit of contextual fear, while JNK1 mainly regulates baseline learning in this behavioral task. Together, these results support the possibility that hippocampal JNKs serve as a critical molecular regulator in the formation of contextual fear.</p>
dc.identifier.submissionpathdavis/27
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages13348-61


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<p>Copyright of all material published in <em>The Journal of Neuroscience</em> remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a <a href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International (CC BY 4.0) license</a>.</p>
Except where otherwise noted, this item's license is described as <p>Copyright of all material published in <em>The Journal of Neuroscience</em> remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a <a href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International (CC BY 4.0) license</a>.</p>