Ionic Currents and Spontaneous Firing in Neurons Isolated from the Cerebellar Nuclei

Neurons of the cerebellar nuclei fire spontaneous action potentials both in vitro, with synaptic transmission blocked, and in vivo, in resting animals, despite ongoing inhibition from spontaneously active Purkinje neurons. We have studied the intrinsic currents of cerebellar nuclear neurons isolated from the mouse, with an interest in understanding how these currents generate spontaneous activity in the absence of synaptic input as well as how they allow firing to continue during basal levels of inhibition. Current-clamped isolated neurons fired regularly ( approximately 20 Hz), with shallow interspike hyperpolarizations (approximately -60 mV), much like neurons in more intact preparations. The spontaneous firing frequency lay in the middle of the dynamic range of the neurons and could be modulated up or down with small current injections. During step or action potential waveform voltage-clamp commands, the primary current active at interspike potentials was a tetrodotoxin-insensitive (TTX), cesium-insensitive, voltage-independent, cationic flux carried mainly by sodium ions. Although small, this cation current could depolarize neurons above threshold voltages. Voltage- and current-clamp recordings suggested a high level of inactivation of the TTX-sensitive transient sodium currents that supported action potentials. Blocking calcium currents terminated firing by preventing repolarization to normal interspike potentials, suggesting a significant role for K(Ca) currents. Potassium currents that flowed during action potential waveform voltage commands had high activation thresholds and were sensitive to 1 mm TEA. We propose that, after the decay of high-threshold potassium currents, the tonic cation current contributes strongly to the depolarization of neurons above threshold, thus maintaining the cycle of firing.