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. Author manuscript; available in PMC: 2008 Jun 29.
Published in final edited form as: Nat Neurosci. 2007 Jul 15;10(8):1012–1019. doi: 10.1038/nn1943

Figure 2.

Figure 2

Increased Cdk5 activity in CK-p25 Tg mice impairs extinction. (a) Experimental design. CK-p25 Tg (n = 9) and control mice (n = 9) were trained by contextual fear conditioning, and p25 expression was induced 24 h later for 1 week. Afterwards, all mice were exposed to six extinction trials before repression of p25 production in CK-p25 Tg by reintroduction of doxycycline to the diet. After 1 week, all mice were subjected to another five extinction trials on consecutive days. (b) Immunoblot analysis of hippocampal lysates from CK-p25 Tg and control mice. Antibody to p35 (C-19) was employed to detected endogenous p25 and p25-GFP in CK-p25 Tg mice 1 week after p25 induction and 1 week after p25 repression, respectively. (c) Cdk5 kinase activity was analyzed by p35 (C-19) immunoprecipitation assays using histone H1 as an in vitro substrate. Cdk5 activity was significantly increased after 1 week of induction, and decreased to baseline levels after 1 week of p25 repression. (d) CK-p25 Tg and control mice were subjected to the experimental procedure described in a. As long as p25 was expressed in CK-p25 Tg, leading to increased Cdk5 activity, the extinction of freezing behavior was abolished. When p25 production was repressed and Cdk5 activity was reduced to baseline levels, extinction occurred in the same mice. ***P < 0.0001, n = 3–5 for biochemical analysis. Error bars represent s.e.m.