Identification of calcineurin as a key signal in the extinction of fear memory

Chih Hung Lin, Shiu Hwa Yeh, Tzeng Horng Leu, Wen Chang Chang, Shan Tair Wang, Po Wu Gean

Research output: Contribution to journalArticlepeer-review

148 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1574-1579
Number of pages6
JournalJournal of Neuroscience
Issue number5
Publication statusPublished - Mar 1 2003


  • Amygdala
  • Calcineurin
  • Fear conditioning
  • Fear-potentiated startle
  • Learning and memory
  • Synaptic plasticity

ASJC Scopus subject areas

  • General Neuroscience


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