This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The central hypothesis of this proposal is that acute stress induces rapid and sustained activation of hippocampal c-Jun-N-terminal kinase (JNK) signaling pathways. This activation of hippocampal JNK pathways is one mechanism mediating stress-induced deficits of contextual fear memory. We also hypothesize that contextual fear conditioning alone activates hippocampal JNKs. JNK activation represents a novel mechanism for regulating consolidation of the contextual fear memory trace. Experiments using constitutive and conditional JNK transgenic mice will delineate the contribution of specific JNK isoforms in mediating fear memory. Our preliminary data using combined biochemical and constitutive transgenic approaches in mutant mice lacking JNK isoform suggest that JNK2 and JNK3 isoforms are involved in stress-induced deficit of fear conditioning, while the JNK1 isoform mainly regulates baseline fear conditioning. To further test these ideas, we will use a chemical-genetic strategy to directly assess the roles of JNKs 1 and 2 in contextual fear conditioning. Specifically, we will make use of mice with a mutation that enables targeted and temporally restricted chemical inhibition of JNK1, JNK2 and JNK3 kinases. We will further test the role of JNK2 and JNK3 using mice with constitutive loss of JNK2/3 expression.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016467-10
Application #
8360696
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
10
Fiscal Year
2011
Total Cost
$68,856
Indirect Cost
Name
University of Hawaii
Department
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
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