A molecular brake controls the magnitude of long-term potentiation

• Published in: Nature communications Vol. 5; no. 1; p. 3051
• Main Authors: Wang, Yubin, Zhu, Guoqi, Briz, Victor, Hsu, Yu-Tien, Bi, Xiaoning, Baudry, Michel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2014; Nature Publishing Group
• Subjects: 631/378/1595/2167; 631/45/474; Animals; Brain-derived neurotrophic factor; Calpain - physiology; Health sciences; Hippocampus - physiology; Humanities and Social Sciences; Kinases; Long-Term Potentiation - physiology; Male; MAP Kinase Signaling System - physiology; Memory; Memory, Long-Term - physiology; multidisciplinary; Neuronal Plasticity - physiology; Nuclear Proteins - physiology; Phosphorylation; Protein synthesis; Proteins; Rats; Rats, Sprague-Dawley; Science; Science (multidisciplinary); United States > US; California
• ISSN: 2041-1723; 2041-1723
• 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 μ-calpain, whereas late SCOP resynthesis is mediated by m-calpain. We propose that μ-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.
Suprachiasmatic nucleus circadian oscillatory protein (SCOP) is implicated in long-term potentiation. Here, the authors show that μ-calpain-mediated SCOP degradation contributes to long-term potentiation induction, whereas m-calpain-mediated stimulation of SCOP synthesis restricts long-term potentiation.