Phase response curves of subthalamic neurons measured with synaptic input and current injection

Abstract

Infinitesimal phase response curves (iPRCs) provide a simple description of the response of repetitively firing neurons and may be used to predict responses to any pattern of synaptic input. Their simplicity makes them useful for understanding the dynamics of neurons when certain conditions are met. For example, the sizes of evoked phase shifts should scale linearly with stimulus strength, and the form of the iPRC should remain relatively constant as firing rate varies. We measured the PRCs of rat subthalamic neurons in brain slices using corticosubthalamic excitatory postsynaptic potentials (EPSPs; mediated by both AMPA- and NMDA-type receptors) and injected current pulses and used them to calculate the iPRC. These were relatively insensitive to both the size of the stimulus and the cell's firing rate, suggesting that the iPRC can predict the response of subthalamic nucleus cells to extrinsic inputs. However, the iPRC calculated using EPSPs differed from that obtained using current pulses. EPSPs (normalized for charge) were much more effective at altering the phase of subthalamic neurons than current pulses. The difference was not attributable to the extended time course of NMDA receptor-mediated currents, being unaffected by blockade of NMDA receptors. The iPRC provides a good description of subthalamic neurons' response to input, but iPRCs are best estimated using synaptic inputs rather than somatic current injection.