  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 the enzyme
protein kinase M (PKM) 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 an stimulus sufficient for LTP and learning
can "capture" PKM. 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 PKM, STC, LTD, and
cross capture, and makes testable predictions concerning the dynamics of PKM.
The maintenance of LTP, and consequently of at least some forms of long-term
memory, is predicted to require continual positive feedback in which PKM
enhances its own synthesis only at potentiated synapses. This feedback
underlies bistability in the activity of PKM. Second, cross capture requires
the induction of LTD to induce dendritic PKM synthesis, although this may
require tagging of a nearby synapse for LTP. The model also simulates the
effects of PKM inhibition, and makes additional predictions for the dynamics of
CaM kinases. Experiments testing the above predictions would significantly
advance the understanding of memory maintenance.
