Translational switch for long-term maintenance of synaptic plasticity.
Memory can last a lifetime, yet synaptic contacts that contribute to the storage of memory are composed of proteins that have much shorter lifetimes. A physiological model of memory formation, long-term potentiation (LTP), has a late protein-synthesis-dependent phase (L-LTP) that can last for many hours in slices or even for days in vivo. Could the activity-dependent synthesis of new proteins account for the persistence of L-LTP and memory? Here, we examine the proposal that a self-sustaining regulation of translation can form a bistable switch that can persistently regulate the on-site synthesis of plasticity-related proteins. We show that an alpha CaMKII-CPEB1 molecular pair can operate as a bistable switch. Our results imply that L-LTP should produce an increase in the total amount of alpha CaMKII at potentiated synapses. This study also proposes an explanation for why the application of protein synthesis and alphaCaMKII inhibitors at the induction and maintenance phases of L-LTP result in very different outcomes.
Aslam
Naveed
N
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
Kubota
Yoshi
Y
Wells
David
D
Shouval
Harel Z
HZ
D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003198:Computer Simulation; D025461:Feedback, Physiological; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology; D008959:Models, Neurological; D014176:Protein Biosynthesis / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
C490386:CPEB1 protein, human; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium