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A hippocampal insulin‐growth factor 2 pathway regulates the extinction of fear memories
Author(s) -
AgisBalboa Roberto Carlos,
ArcosDiaz Dario,
Wittnam Jessica,
Govindarajan Nambirajan,
Blom Kim,
Burkhardt Susanne,
Haladyniak Ulla,
Agbemenyah Hope Yao,
Zovoilis Athanasios,
SalinasRiester Gabriella,
Opitz Lennart,
Sananbenesi Farahnaz,
Fischer Andre
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.293
Subject(s) - biology , hippocampal formation , extinction (optical mineralogy) , neuroscience , insulin , insulin like growth factor , growth factor , endocrinology , genetics , receptor , paleontology
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 extinction‐induced 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.