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The Journal of Neuroscience, March 1, 2003, 23(5):1574

BRIEF COMMUNICATION
Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory

Chih-Hung Lin¹, Shiu-Hwa Yeh¹, Tzeng-Horng Leu¹, Wen-Chang Chang¹, Shan-Tair Wang², and Po-Wu Gean¹

Departments of ¹ Pharmacology and ² Public Health, College of Medicine, National Cheng-Kung University, Tainan City, Taiwan 701

Memory extinction refers to a gradual decrease of the previously acquired response when exposed to conditional stimulus without pairing with unconditional stimulus. Here we show for the first time that fear training-induced phosphorylation of specific substrates in the rat amygdala is reduced after extinction trials and is accompanied by an increase in the protein level and enzymatic activity of calcineurin. In parallel, calcineurin inhibitors prevented extinction-induced protein dephosphorylation as well as extinction of fear memory. Thus, extinction training increased phosphatase activity likely via an expression of calcineurin. Calcineurin then created a negative-feedback loop and directly or indirectly dephosphorylated specific substrates, which, in their phosphorylated state, were required for memory consolidation. Accordingly, in our experimental condition, extinction could be ascribed at least in part to a weakening of the original signaling.

Key words: learning and memory; amygdala; calcineurin; synaptic plasticity; fear conditioning; fear-potentiated startle

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2351574-06$05.00/0

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