Cui J, Canavier CC, Butera RJ. Functional phase response curves: a method for understanding synchronization of adapting neurons (2009) J Neurophysiol, 102: 387–398.

Phase response curves (PRCs) for a single neuron are often used to predict the synchrony of mutually coupled neurons. Previous theoretical work on pulse-coupled oscillators used single-pulse perturbations. We propose an alternate method in which functional PRCs (fPRCs) are generated using a train of pulses applied at a fixed delay after each spike, with the PRC measured when the phasic relationship between the stimulus and the subsequent spike in the neuron has converged. The essential information is the dependence of the recovery time from pulse onset until the next spike as a function of the delay between the previous spike and the onset of the applied pulse. Experimental fPRCs in Aplysia pacemaker neurons were different from single-pulse PRCs, principally due to adaptation. In the biological neuron, convergence to the fully adapted recovery interval was slower at some phases than that at others because the change in the effective intrinsic period due to adaptation changes the effective phase resetting in a way that opposes and slows the effects of adaptation. The fPRCs for two isolated adapting model neurons were used to predict the existence and stability of 1: 1 phase-locked network activity when the two neurons were coupled. A stability criterion was derived by linearizing a coupled map based on the fPRC and the existence and stability criteria were successfully tested in two-simulated-neuron networks with reciprocal inhibition or excitation. The fPRC is the first PRC-based tool that can account for adaptation in analyzing networks of neural oscillators.