Ionic currents and spiking in cerebellar nuclear neurons

描述（由申请人提供）：小脑核的神经元是自发活动的神经元，整合来自苔藓纤维的兴奋性输入和来自浦肯野神经元的抑制性输入，产生小脑的输出。浦肯野输入的强度和程度提出了抑制如何与兴奋和内在放电相互作用以调节小脑输出的问题。因为浦肯野细胞可以在小脑行为中同步它们的简单尖峰，很可能小脑核神经元对抑制输入的同步性做出反应，浦肯野细胞更多的时间分散抑制提供了更有效的核细胞尖峰分流，更多的同步抑制导致了允许尖峰发生的净抑制的减少。目前的提议旨在检验这一想法

DESCRIPTION (provided by applicant): 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. The strength and extent of Purkinje input raise the question of how inhibition interacts with excitation and intrinsic firing to regulae cerebellar output. Because Purkinje cells can synchronize their simple spikes during cerebellar behaviors, it is likely that cerebellar nuclear neurons respond to the degree of synchrony of inhibitory inputs, with more temporally dispersed inhibition from Purkinje cells providing a more effective shunt of nuclear cell spiking, and more synchronized inhibition leading to reductions in net inhibition that allow spikes to occur. The present proposal is directed toward testing the idea that inhibitory synchrony has a significant effect on dictating cerebellar output under normal conditions, as well as toward examining the possibility that Purkinje-to-nuclear cell signaling may be modulated naturally or change under pathophysiological conditions. Experiments will be performed both in vitro and in vivo, on normal and mutant mice and in zebrafish. Voltage-clamp, current-clamp, and extracellular recordings will be used to test the interaction of excitatory with inhibitory inputs, the consequences of modulating Purkinje inputs, and the effect of sensory input on Purkinje synchrony and nuclear cell output.