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Mol Neurobiol. 2016 Mar;53(2):1247-53. doi: 10.1007/s12035-015-9093-6. Epub 2015 Jan 24.

Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

Author information

1
Mental Health Institute, The 2nd Xiangya Hospital, Key Lab of Psychiatry and Mental Health of Hunan Province, Central South University, 132 Ren-Ming Road, Changsha, 410011, China.
2
Neurology, Kunming Affiliated Hospital of Dali University, Kunming, 650011, China.
3
Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, 32 Jiao-Chang Dong Road, Kunming, 650223, China.
4
Key Laboratory of Arrhythmias, Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
5
Department of Physiology, Kunming Medical University, Kunming, 650031, China.
6
Institute of Mental Health Research and Departments of Psychiatry and Cellular & Molecular Medicine, University of Ottawa, 1145 Carling Ave, Ottawa, Ontario, K1Z 7K4, Canada.
7
Mental Health Institute, The 2nd Xiangya Hospital, Key Lab of Psychiatry and Mental Health of Hunan Province, Central South University, 132 Ren-Ming Road, Changsha, 410011, China. llj2920@163.com.
8
Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, 32 Jiao-Chang Dong Road, Kunming, 650223, China. lxu@vip.163.com.

Abstract

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.

KEYWORDS:

Contextual fear memory; Forgetting; GTPase Rac1; Hippocampus; Hypermnesia

PMID:
25613020
DOI:
10.1007/s12035-015-9093-6
[Indexed for MEDLINE]

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