Ionic currents and spiking in cerebellar nuclear neurons

Neurons of the cerebellar nuclei are spontaneously active neurons that integrate excitatory input from mossy fibers and inhibitory input from Purkinje neurons to generate the output of the cerebellum. In real time, cerebellar output corrects errors and facilitates learned, coordinated movements, raising the question of how inhibition, excitation, and intrinsic firing interact to regulate the firing patterns of cerebellar nuclear cells. The present proposal is directed toward testing the idea that nuclear cells’ response to Purkinje-mediated inhibition varies according to the correction or regulation produced by the cerebellum at any time. In particular, the degree of inhibitory synchrony may dictate cerebellar output in a task-dependent manner. Experiments will be performed both in vitro and in vivo, in normal and mutant mice and in zebrafish. Voltage-clamp, current-clamp, and extracellular electrophysiological recordings will be used to test the changes in correlation of Purkinje and nuclear cell activity during practiced motor behaviors and during errors, the interaction of excitatory with inhibitory inputs, and the changes in Purkinje synchrony and nuclear cell output during learning.