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 gener ate spontaneous activity in the absence of synaptic input as well as how th ey allow firing to continue during basal levels of inhibition. Current-clam ped isolated neurons fired regularly (similar to 20 Hz), with shallow inter spike 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 sma ll current injections. During step or action potential waveform voltage-clamp commands, the primar y current active at interspike potentials was a tetrodotoxin-insensitive (T TX), cesium-insensitive, voltage-independent, cationic flux carried mainly by sodium ions. Although small, this cation current could depolarize neuron s above threshold voltages. Voltage- and current-clamp recordings suggested a high level of inactivation of the TTX-sensitive transient sodium current s that supported action potentials. Blocking calcium currents terminated fi ring by preventing repolarization to normal interspike potentials, suggesti ng a significant role for K(Ca) currents. Potassium currents that flowed du ring action potential waveform voltage commands had high activation thresho lds and were sensitive to 1 mM TEA. We propose that, after the decay of hig h-threshold potassium currents, the tonic cation current contributes strong ly to the depolarization of neurons above threshold, thus maintaining the c ycle of firing.