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Late long-term potentiation (L-LTP) appears essential for the formation oflong-term memory, with memories at least partly encoded by patterns ofstrengthened synapses. How memories are preserved for months or years, despitemolecular turnover, is not well understood. Ongoing recurrent neuronalactivity, during memory recall or during sleep, has been hypothesized topreferentially potentiate strong synapses, preserving memories. This hypothesishas not been evaluated in the context of a mathematical model representingbiochemical pathways important for L-LTP. I incorporated ongoing activity intotwo such models: a reduced model that represents some of the essentialbiochemical processes, and a more detailed published model. The reduced modelrepresents synaptic tagging and gene induction intuitively, and the detailedmodel adds activation of essential kinases by Ca. Ongoing activity was modeledas continual brief elevations of [Ca]. In each model, two stable states ofsynaptic weight resulted. Positive feedback between synaptic weight and theamplitude of ongoing Ca transients underlies this bistability. A tetanic ortheta-burst stimulus switches a model synapse from a low weight to a highweight stabilized by ongoing activity. Bistability was robust to parametervariations. Simulations illustrated that prolonged decreased activity resetsynapses to low weights, suggesting a plausible forgetting mechanism. However,episodic activity with shorter inactive intervals maintained strong synapses.Both models support experimental predictions. Tests of these predictions areexpected to further understanding of how neuronal activity is coupled tomaintenance of synaptic strength.

A Model of Late Long-Term Potentiation Simulates Aspects of Memory Maintenance