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性神经元，其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以产生小脑的输出。浦肯野输入的强度和范围提出了抑制如何与兴奋和内在放电相互作用来调节小脑输出的问题。由于浦肯野细胞可以在小脑行为期间同步它们的简单尖峰，因此小脑核神经元可能对抑制性输入的同步程度做出反应，来自浦肯野细胞的时间分散的抑制提供了更有效的核细胞尖峰分流，并且更同步的抑制导致允许尖峰发生的净抑制减少。目前的建议是针对测试的想法 在正常情况下，抑制性同步对支配小脑输出有显著影响，以及检查浦肯野-核细胞信号传导可能在病理生理条件下自然调节或改变的可能性。 实验将在体外和体内进行，在正常和突变小鼠和斑马鱼。电压钳、电流钳和细胞外记录将用于测试兴奋性输入与抑制性输入的相互作用、调节浦肯野输入的后果以及感觉输入对浦肯野同步性和核细胞输出的影响。

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.