Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory
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Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus.
KeywordsGTPase Rac1 Hypermnesia Hippocampus Forgetting Contextual fear memory
Posttraumatic stress disorder
We thank LP Wang for technical assistance and Lab members for their critical comments. This work was supported by the National Basic Research Program of China (2013CB835103 and 2009CB918303), Strategic Priority Research Program of the Chinese Academy of Science (XDB02020002), NSFC-CIHR Joint Grant (81161120536), National Natural Science Foundation of China (31100786, 30860089, 930830046, 81171286, 91232714, 81460216, U1032605, and U1132602), and Science and Technology Program of Yunnan Province (2013GA003 and 2013FA048). There are no competing financial interests in relation to the work.
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