Activation of Fyn tyrosine kinase in the mouse dorsal hippocampus is essential for contextual fear conditioning

Tomoko Isosaka, Kotaro Hattori, Satoshi Kida, Tomoko Kohno, Takanobu Nakazawa, Tadashi Yamamoto, Takeshi Yagi, Shigeki Yuasa

研究成果: Article査読

38 被引用数 (Scopus)


Fyn-tyrosine-kinase-deficient mice exhibit defects in the Morris water maze test and long-term potentiation (LTP) induction in the hippocampus, and given that LTP has been postulated as the neural basis for memory formation, Fyn may be required for hippocampus-dependent memory formation. However, how Fyn is involved in the process of memory formation is unclear. To investigate the role of Fyn in hippocampal memory formation, we first tested the behavior of Fyn-deficient mice by contextual fear conditioning. A mouse was placed in a context and a foot shock was delivered, so that the mouse associated the context with the shock. We found that the freezing response of Fyn-deficient mice to the context was impaired at 24 h after conditioning. We then measured freezing at 1 h after conditioning, and found that their short-term contextual fear memory was also impaired. We used Western blotting to examine the mode of Fyn activation in dorsal hippocampal tissue following contextual fear conditioning. Fyn activation peaked as early as 5-10 min after contextual fear conditioning and persisted for at least 40 min. Concomitant increases in tyrosine phosphorylation of several proteins, including NR2B, were also observed, but no increases in tyrosine phosphorylation were observed in Fyn-deficient mice. Thus, both short-term and long-term (24-h) contextual fear memory were impaired in Fyn-deficient mice, and Fyn activation in the dorsal hippocampus transiently increased after contextual fear conditioning. These findings strongly suggest that activation of the Fyn signaling pathway is involved in hippocampus- dependent formation of contextual fear memory.

ジャーナルEuropean Journal of Neuroscience
出版ステータスPublished - 2008 9

ASJC Scopus subject areas

  • Neuroscience(all)

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