Hippocampal Fyn activity regulates extinction of contextual fear.
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.
Isosaka
Tomoko
T
Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Kida
Satoshi
S
Kohno
Tomoko
T
Hattori
Kotaro
K
Yuasa
Shigeki
S
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
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