title: Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.
abstract: Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.
authors.affiliation: Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School at Houston, Houston, Texas, United States of America. Paul.D.Smolen@uth.tmc.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Smolen
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Baxter
authors.forename: John H
authors.initials: JH
authors.lastname: Byrne
mesh_terms: D006801:Humans; D017774:Long-Term Potentiation; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D013269:Stochastic Processes; D013569:Synapses / Q000201:enzymology / Q000502:physiology*
chemical_list: D011493:Protein Kinase C