Synaptic Coding in the Cerebellar Corticonuclear Circuit

小脑皮质核回路中的突触编码

• 批准号: 10612364
• 负责人: Indira M Raman
• 金额: $ 65.98万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612364
• 关键词: Association Learning; Ataxia; Behavior; Behavioral; Biophysics; Brain region; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Code; Dyslexia; Dystonia; Environment; Functional disorder; In Vitro; Learning; Link; Monitor; Motor; Motor Neurons; Movement; Mus; Neurons; Output; Pathologic; Pattern; Physiological; Physiology; Process; Purkinje Cells; Sensory; Signal Transduction; Synapses; Time; Work; Zebrafish; autism spectrum disorder; biophysical analysis; comparative; habituation; in vivo; mossy fiber; motor behavior; motor learning; neurotransmission; response; sensory input; transmission process

Project Summary/Abstract 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 小脑核运动前神经元(CBN)是整合兴奋性神经元的自发活动神经元 抑制性输入，主要来自苔藓纤维和浦肯野神经元，以产生小脑的输出。 小脑有助于协调运动和实时纠正错误，也可以改变学习方式 随着时间的推移，新的运动模式。这些观察提出了一个问题，即突触输入是如何调节内在的 以一种允许运动前CBN神经元识别与预测感觉输入的偏差的方式进行放电 对适当的纠正输出进行编码。我们正在研究生物物理和突触机制 限制和确定CBN细胞在体外响应突触输入的生理模式的激发模式 以及在活体运动行为过程中预期或意外的感觉输入。最近的研究表明， 汇聚的浦肯野细胞的抑制同步性程度可能决定小鼠的小脑输出 条件依赖的方式。因此，我们将研究小鼠和幼虫的小脑生理和行为。 斑马鱼，提供了一种比较的方法，包括体外和体内。浦肯野和CBN细胞的放电模式将 在良好学习的、可预测的运动行为期间、在不可预测的感觉输入期间，以及 在习惯化和联想条件反射等运动学习过程中。观察结果将与以下内容相关 兴奋性和抑制性传入相互作用的突触研究，汇聚和连接，以及短... 长期和长期的可塑性。生物物理和行为水平的这种联系将有助于解释 小脑回路对预测偏差产生适应性反应的机制， 从而促进了执行良好的动作。