title: A molecular brake controls the magnitude of long-term potentiation.
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.
authors.affiliation: 1] Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA [2].
authors.forename: Yubin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA [2].
authors.forename: Guoqi
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Briz
authors.affiliation: Stanford Institute of NeuroInnovation and Translational Neuroscience, Stanford University, Stanford, California 94305-5453, USA.
authors.forename: Yu-Tien
authors.initials: YT
authors.lastname: Hsu
authors.affiliation: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Bi
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California 91766, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Baudry
mesh_terms: D000818:Animals; D002154:Calpain / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology*; D010749:Phosphoprotein Phosphatases; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009687:Nuclear Proteins; C553451:PHLPP1 protein, rat; D010749:Phosphoprotein Phosphatases; D002154:Calpain; C449000:m-calpain; C449002:mu-calpain