Synaptic Coding in the Cerebellar Corticonuclear Circuit

小脑皮质核回路中的突触编码

• 批准号: 10381507
• 负责人: Indira M Raman
• 金额: $ 66.21万
• 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/10381507
• 关键词: Ataxia; Behavior; Behavioral; Biophysics; Brain region; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Code; Dyslexia; Dystonia; Environment; Functional disorder; In Vitro; Learning; Link; Monitor; Motor; Movement; Mus; Neurons; Output; Pathologic; Pattern; Physiological; Physiology; Process; Purkinje Cells; Sensory; Signal Transduction; Synapses; Time; Work; Zebrafish; autism spectrum disorder; biophysical analysis; classical conditioning; comparative; habituation; in vivo; mossy fiber; motor behavior; motor learning; neurotransmission; response; sensory input

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.

项目总结/摘要 小脑核前运动神经元（CbN）是一种自发活动的神经元， 和抑制性输入，主要来自苔藓纤维和浦肯野神经元，以产生小脑的输出。 小脑促进协调的运动和纠正错误在真实的时间，也改变学习 随着时间的推移，新的运动模式。这些观察结果提出了一个问题，即突触输入如何调节内在的 以允许前运动CbN神经元识别与预测的感觉输入的偏差的方式放电， 编码适当的纠正输出。我们正在研究生物物理和突触机制， 在体外限制和定义响应于突触输入的生理模式的CbN细胞放电模式 以及在体内运动行为期间预期或非预期的感觉输入。最近的研究表明， 会聚性浦肯野细胞的抑制性同步程度可能决定了小鼠小脑的输出， 条件依赖的方式。因此，我们将研究小鼠和幼虫的小脑生理学和行为。 斑马鱼，以提供体外和体内的比较方法。浦肯野细胞和CbN细胞的放电模式 在学习良好、可预测的运动行为期间，在不可预测的感觉输入期间， 在运动学习过程中，如习惯化和联想条件反射。观察结果将与 兴奋性与抑制性输入的相互作用、会聚和连接以及短- 长期和长期塑性。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， 从而有助于良好执行的运动。