Parameterized phase response curves for characterizing neuronal behaviors under transient conditions.

Phase response curves (PRCs) are a simple model of how a neuron's spike time is affected by synaptic inputs. PRCs are useful in predicting how networks of neurons behave when connected. One challenge in estimating a neuron's PRCs experimentally is that many neurons do not have stationary firing rates. In this article we introduce a new method to estimate PRCs as a function of firing rate of the neuron. We call the resulting model a parameterized PRC (pPRC). Experimentally, we perturb the neuron applying a current with two parts: 1) a current held constant between spikes but changed at the onset of a spike, used to make the neuron fire at different rates, and 2) a pulse to emulate a synaptic input. A model of the applied constant current and the history is made to predict the interspike interval (ISI). A second model is then made to fit the modulation of the spike time from the expected ISI by the pulsatile stimulus. A polynomial with two independent variables, the stimulus phase and the expected ISI, is used to model the pPRC. The pPRC is validated in a computational model and applied to pyramidal neurons from the CA1 region of the hippocampal slices from rat. The pPRC can be used to model the effect of changing firing rates on network synchrony. It can also be used to characterize the effects of neuromodulators and genetic mutations (among other manipulations) on network synchrony. It can also easily be extended to account for more variables.