Biophysical model of synaptic plasticity dynamics

We discuss a biophysical model of synaptic plasticity that provides a unified view of the outcomes of synaptic modification protocols, including: (1) prescribed time courses of postsynaptic intracellular Ca2+ release, (2) postsynaptic voltage clamping with presentation of presynaptic spike trains at various frequencies, (3) direct postsynaptic response to presynaptic spike trains at various frequencies, and (4) LTP/LTD as a response to precisely timed presynaptic and postsynaptic spikes. Our model has a Hodgkin-Huxley conductance-based neuron with AMPA and NMDA channels and voltage-gated calcium channels in addition to the usual currents. The time course of intracellular concentration of Ca2+ is determined by fluxes from these three sources and drives a competition of kinase and phosphatase pathways. Our critical assumption is a phenomenological form for the competition of kinase and phosphatase activity leading to changes in synaptic strength. This is examined in the context of experiments that induce plasticity by programmed postsynaptic intracellular Ca2+ release. It is successful in describing such experiments. This connection is used in conjunction with a biophysical model of postsynaptic membrane voltage and Ca2+ fluxes to show that the features of the other protocols are consequences of the model. We then use the model to predict the outcome of new experiments: (a) LTP/LTD spike timing plasticity in the presence of varying extracellular concentrations of Mg2+, (b) the response of synaptic strength to the presentation of concurrent presynaptic and postsynaptic spike trains, and (c) spike timing plasticity with two presynaptic (postsynaptic) spikes and one postsynaptic (presynaptic) spike.