“We knew that LTP requires BDNF release,” Baudry said. “BDNF activates m-calpain; m-calpain cleaves this PTEN protein, which produces stimulation of local protein synthesis. But we still had not shown that LTP directly engages m-calpain.”
This paper addresses the respective roles of mu- and m-calpain in the mechanisms underlying LTP, and therefore learning and memory.
Overexpression of suprachiasmatic nucleus circadian oscillatory protein (SCOP), a negative ERK regulator, had been shown to block long-term memory encoding.
Inhibition of calpain-mediated SCOP degradation also prevents the formation of long-term memory, suggesting that calpain-mediated SCOP breakdown is necessary for memory encoding. However, whether SCOP levels also control the magnitude of LTP was unknown.
“We report here the surprising finding that LTP induction produces rapid µ-calpain-mediated SCOP degradation, while SCOP re-synthesis during a one-hour period following LTP induction is mediated by m-calpain-induced PTEN degradation and stimulation of local protein synthesis,” according to the study.
“We propose that mu-calpain promotes long-term potentiation induction by degrading SCOP and activating a protein kinase, which has been repeatedly shown to be involved in synaptic plasticity and memory formation, the extracellular signal-regulated kinase, ERK, while 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 vs. massed training in the formation of long-term memory.”
The Baudry lab had been struggling to convince the scientific community that calpain was playing a critical role
Copyright©2012 Vocus, Inc.
All rights reserved