A biophysical basis for the inter-spike interaction of spike-timing-dependent plasticity.

Although spike-timing-dependent plasticity (STDP) is well characterized when pre- and postsynaptic spikes are paired with a given time lag, how this generalizes for more complex spike-trains is unclear. Recent experiments demonstrate that contributions to synaptic plasticity from different spike pairs within a spike train do not add linearly. In the visual cortex conditioning with spike triplets shows that the effect of the first spike pair dominates over the second. Using a previously proposed calcium-dependent plasticity model, we show that short-term synaptic dynamics and interaction between successive back-propagating action potentials (BPAP) may jointly account for the nonlinearities observed. Paired-pulse depression and attenuation of BPAPs are incorporated into the model through the use-dependent depletion of pre- and postsynaptic resources, respectively. Simulations suggest that these processes may play critical roles in determining how STDP operates in the context of natural spike-trains.