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The replenishment rates estimated from the recovery of synaptic efficacy following synaptic depression are known to be widely scattered. Given the importance of the replenishment during stimulation, especially if it is prolonged, it is important to better understand what influences the recovery of the synaptic efficacy following stimulation. We fit a two-pool model of vesicular secretion to the changes of the excitatory post-synaptic currents recorded in CA1 neurons of rat hippocampal slices to determine how the model parameters change during, and following, long stimulation. The replenishment rate at the end of stimulation inducing synaptic depression differs greatly from that at the beginning of stimulation. It decreases progressively and rapidly (by ~75 % and with a time constant of &lt;10 s) during stimulation, and this is followed by a similarly fast recovery (time constant of ~10 s), but to a steady-state that is approximately twice as large as its pre-stimulation value. Both [Ca(++)]o and the duration of long stimulation influence the recovery of the replenishment rate. Its new steady-state is significantly higher, if either [Ca(++)]o is higher or stimulation longer, but the recovery of the replenishment rate becomes clearly slower if [Ca(++)]o is higher, and faster if stimulation is longer. Many factors thus influence the recovery of the replenishment rate and of the synaptic efficacy, but the stimulation induced [Ca(++)]i accumulation cannot explain the change of the replenishment rate during recovery. Finally, okadaic acid, which speeds up vesicular trafficking, does not alter the recovery of the replenishment rate. The vesicular replenishment of the RRP following stimulation is thus not likely to be associated with significant vesicular movement.

Recovery of vesicular storage and release parameters after high frequency stimulation in rat hippocampus