期刊
EMBO JOURNAL
卷 30, 期 19, 页码 4071-4083出版社
WILEY
DOI: 10.1038/emboj.2011.293
关键词
fear extinction; gene expression; hippocampus; learning and memory; mouse models
资金
- European Science Foundation
- German-Research-Foundation (DFG) [SA1050/2-1]
- EMBO
- Hans and Ilse Breuer Foundation
- University Medicine Gottingen
- Max Planck Society
Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example, the expression of an aversive behaviour upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinction are only beginning to emerge. Here, we show that fear extinction initiates upregulation of hippocampal insulin-growth factor 2 (Igf2) and downregulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation, we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2 signalling during fear extinction. To this end, we show that fear extinctioninduced IGF2/IGFBP7 signalling promotes the survival of 17-19-day-old newborn hippocampal neurons. In conclusion, our data suggest that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. The EMBO Journal (2011) 30, 4071-4083. doi:10.1038/emboj.2011.293; Published online 26 August 2011
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