Ionic currents and spiking in cerebellar nuclear neurons

描述(申请人提供)：小脑核团的神经元是自发活动的神经元，它整合苔藓纤维的兴奋性输入和浦肯野神经元的抑制性输入，产生小脑的输出。实时地，小脑的输出纠正错误并促进习得的、协调的运动，这就提出了抑制、兴奋和内在放电如何相互作用来调节小脑的放电模式的问题。 核细胞。目前的建议是为了验证这样一种想法，即核细胞对浦肯野介导的抑制的反应在任何时候都会随着小脑产生的纠正或调节而变化。特别是，抑制同步性的程度可能以一种任务依赖的方式决定小脑的输出。实验将在体外和体内、正常和突变小鼠以及斑马鱼身上进行。我们将使用电压钳、电流钳和细胞外电生理记录来测试在练习运动行为和错误过程中浦肯野与核细胞活动相关性的变化，兴奋性和抑制性输入的相互作用，以及学习过程中浦肯野同步性和核细胞输出的变化。

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. 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.