The voltage-gated Na+ currents near threshold voltages will be studied in Purkinje neurons of the cerebellum, with a general interest in understanding how interaction among ionic currents determine action potential threshold and produce different patterns of activity. Purkinje cells form the sole output of the cerebellar cortex and show a range of spiking behaviors. Although their activity plays a central role in motor behavior and motor learning and disruption of their activity results in sever motor deficits, relatively little research has made use of modern electrophysiological techniques to investigate how ionic currents control normal Purkinje cell firing. The proposed experiments will be done on Purkinje cells enzymatically isolated from rat cerebellum. First, using whole-cell voltage clamping and cell attached single-channel recording, the properties of transient, persistent, and the novel resurgent Na+ currents will be described. Next, current-clamp recording will be used to study the parameters that shape threshold in Purkinje cells. Finally, the recorded waveforms of simple spikes, complex spikes, and trains of spikes will be used as voltage-clamp protocols to measure how changes in the relative amplitude and depolarizing strength of each aspect of Na+ current (transient, persistent, and resurgent) can modify threshold and evoke different patterns of spiking.
| Raman, I M; Sprunger, L K; Meisler, M H et al. (1997) Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Neuron 19:881-91 |
