title: Hippocampal Fyn activity regulates extinction of contextual fear.
abstract: Contextual fear memory is attenuated by reexposure of animals to a context alone without pairing it with an unconditioned stimulus, a phenomenon referred to as fear extinction. Here, we report that Fyn tyrosine kinase in the hippocampus is involved in the extinction of contextual fear. We inhibited Src-family tyrosine kinases in the dorsal hippocampus by stereotaxic injection of an inhibitor, PP2, and observed facilitation of extinction. We then biochemically analyzed dorsal hippocampal tissue during extinction training, and found that activated Fyn was significantly downregulated among the Src-family tyrosine kinases examined. These findings suggest that downregulation of Fyn activity facilitates the extinction of contextual fear.
authors.affiliation: Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Isosaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohno
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yuasa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D013997:Time Factors
chemical_list: C509621:4-amino-7-phenylpyrazol(3,4-d)pyrimidine; C412373:AG 1879; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn