RT Journal Article
SR Electronic
T1 Identification of Calcineurin as a Key Signal in the Extinction of Fear Memory
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1574
OP 1579
DO 10.1523/JNEUROSCI.23-05-01574.2003
VO 23
IS 5
A1 Lin, Chih-Hung
A1 Yeh, Shiu-Hwa
A1 Leu, Tzeng-Horng
A1 Chang, Wen-Chang
A1 Wang, Shan-Tair
A1 Gean, Po-Wu
YR 2003
UL http://www.jneurosci.org/content/23/5/1574.abstract
AB 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.