Admin Supplement-Landis Award: Synaptic Coding in the Cerebellar Corticonuclear Circuit

管理补充-兰迪斯奖：小脑皮质核回路中的突触编码

基本信息

批准号：
10893696
负责人：
Indira M Raman
金额：
$ 16万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-04-30
项目状态：
未结题

项目摘要

Project Summary/Abstract (unchanged from parent proposal) Premotor neurons of the cerebellar nuclei (CbN) are spontaneously active neurons that integrate excitatory and inhibitory input, largely from mossy fibers and Purkinje neurons, to generate the output of the cerebellum. The cerebellum facilitates coordinated movement and corrects errors in real time, and also changes to learn new motor patterns over time. These observations raise the question of how synaptic input modulates intrinsic firing in a manner that permits premotor CbN neurons to identify deviations from predicted sensory input and encode appropriate corrective outputs. We are studying the biophysical and synaptic mechanisms that constrain and define patterns of CbN cell firing in response to physiological patterns of synaptic input in vitro and expected or unexpected sensory input during motor behaviors in vivo. Recent work suggests that the degree of inhibitory synchrony from convergent Purkinje cells may dictate cerebellar output in mice in a condition-dependent manner. We will therefore study cerebellar physiology and behavior in mice and in larval zebrafish, to provide a comparative approach, both in vitro and in vivo. Purkinje and CbN cell firing patterns will be monitored both during well-learned, predictable motor behaviors, during unpredicted sensory inputs, and during motor learning such as habituation and associative conditioning. The observations will be related to synaptic studies of the interaction of excitatory with inhibitory inputs, convergence and connectivity, and short- term and long-term plasticity. Such linking of the biophysical and behavioral levels will help explain the mechanisms by which the cerebellar circuit produces adaptive responses to deviations from predictions, thereby facilitating well-executed movement.

项目摘要/摘要（与父母提案不变）小脑核（CBN）的前神经元是自发活跃的神经元，可以整合兴奋性抑制性输入很大程度上来自苔藓纤维和浦肯野神经元，以产生小脑的输出。小脑促进了协调的运动并实时纠正错误，也会改变以学习随着时间的推移，新的电机图案。这些观察结果提出了突触输入如何调节固有的问题以允许前CBN神经元识别偏离预测的感觉输入和编码适当的纠正输出。我们正在研究生物物理和突触机制根据体外突触输入的生理模式，约束和定义CBN细胞发射的模式在体内运动行为期间的预期或意外感觉输入。最近的工作表明来自聚合Purkinje细胞的抑制性同步程度可能决定小鼠在A中的小脑输出条件依赖性方式。因此，我们将研究小鼠和幼虫的小脑生理和行为斑马鱼，在体外和体内提供一种比较方法。 Purkinje和CBN电池发射模式将在良好的，可预测的运动行为，在不可预测的感觉输入期间和在运动学习期间，例如习惯和联想条件。观察将与突触研究兴奋与抑制性投入，收敛和连通性以及短期的相互作用术语和长期可塑性。生物物理和行为水平的这种联系将有助于解释小脑回路产生对预测偏差的自适应反应的机制从而促进了执行良好的运动。