A molecular brake controls the magnitude of long-term potentiation

作者：Wang Yubin; Zhu Guoqi; Briz Victor; Hsu Yu Tien; Bi Xiaoning; Baudry Michel^*

来源：Nature Communications, 2014, 5(1): 3051.

DOI：10.1038/ncomms4051

Overexpression of suprachiasmatic nucleus circadian oscillatory protein (SCOP), a negative ERK regulator, blocks long-term memory encoding. Inhibition of calpain-mediated SCOP degradation also prevents the formation of long-term memory, suggesting rapid SCOP breakdown is necessary for memory encoding. However, whether SCOP levels also control the magnitude of long-term synaptic plasticity is unknown. Here we show that following synaptic activity-induced SCOP degradation, SCOP is rapidly replaced via mTOR-mediated protein synthesis. We further show that early SCOP degradation is specifically catalysed by m-calpain, whereas late SCOP resynthesis is mediated by m-calpain. We propose that m-calpain promotes long-term potentiation induction by degrading SCOP and activating ERK, whereas m-calpain activation limits the magnitude of potentiation by terminating the ERK response via enhanced SCOP synthesis. This unique braking mechanism could account for the advantages of spaced versus massed training in the formation of long-term memory.

• 出版日期2014-1