JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory
Authors
Morel, CarolineSherrin, Tessi
Kennedy, Norman J.
Forest, Kelly H.
Barutcu, Seda
Robles, Michael
Carpenter-Hyland, Ezekiel
Alfulaij, Naghum
Standen, Claire L.
Nichols, Robert A.
Benveniste, Morris
Davis, Roger J.
Todorovic, Cedomir
UMass Chan Affiliations
UMass Metabolic NetworkGraduate School of Biomedical Sciences
Davis Lab
Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2018-04-11Keywords
JIP1JNK
LTP
fear
memory
plasticity
Amino Acids, Peptides, and Proteins
Cell Biology
Cellular and Molecular Physiology
Developmental Biology
Enzymes and Coenzymes
Molecular and Cellular Neuroscience
Molecular Biology
Metadata
Show full item recordAbstract
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.Source
J Neurosci. 2018 Apr 11;38(15):3708-3728. doi: 10.1523/JNEUROSCI.1913-17.2018. Epub 2018 Mar 14. Link to article on publisher's site
DOI
10.1523/JNEUROSCI.1913-17.2018Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29261PubMed ID
29540552Related Resources
Rights
Copyright © 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.ae974a485f413a2113503eed53cd6c53
10.1523/JNEUROSCI.1913-17.2018