Stimulus-dependent induction of long-term potentiation in CA1 area of the hippocampus: experiment and model.

In the CA1 area of the hippocampus, the magnitude of long-term potentiation (LTP) depends not only on the frequency of applied stimuli, but also on their number. With a slice preparation using extracellular recording in the hippocampus CA1 of a guinea pig, we investigate the magnitude of LTP induced by electrical stimuli with a range of frequencies and the number of applied stimuli. We find that the magnitude of the saturated potentiation obtained with periodic stimuli largely depends on the frequency and is insensitive to the number of stimuli, once the saturation level has been obtained. Furthermore, we investigated nonperiodic stimuli and found that the magnitude of the saturated potentiation is also sensitive to the statistical correlation between successive interstimulus intervals, even when their average frequency is held constant. In order to explain the LTP dependence on these various experimental parameters, we propose a simple mathematical model for the induction of LTP. In the model, an exponentially decaying element released as a result of previous stimuli is coupled with a new stimulus to act as the potentiation force, and the magnitude of potentiation is determined by this potentiation force. We can determine the decaying time constant of this hypothetical element as a model parameter by fitting the model to the experimental data. The time scale is found to be of the order of 200 msc. A molecular or cellular factor with this decaying time constant is likely to be induced in LTP induction.