Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Commun. 2014;5:3051. doi: 10.1038/ncomms4051.

A molecular brake controls the magnitude of long-term potentiation.

Author information

1
1] Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA [2].
2
Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA.
3
Stanford Institute of NeuroInnovation and Translational Neuroscience, Stanford University, Stanford, California 94305-5453, USA.
4
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.

Abstract

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.

PMID:
24394804
PMCID:
PMC3895372
DOI:
10.1038/ncomms4051
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center