Mechanisms of timing and temporal coding

定时和时间编码机制

• 批准号: 10367024
• 负责人: MICHAEL D MAUK
• 金额: $ 38.92万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367024
• 关键词: Animals; Axon; Back; Behavioral; Biological; Brain; Cells; Cerebellar Cortex; Cerebellar Nuclei; Cerebellum; Code; Conditioned Reflex; Coupling; Cytoplasmic Granules; Data; Data Analyses; Disease; Dyslexia; Extinction (Psychology); Feedback; Genetic; Golgi Apparatus; Impairment; Learning; Methods; Neurons; Noise; Output; Physiology; Play; Process; Property; Recurrence; Resistance; Role; Synapses; System; Testing; Time; Training; autism spectrum disorder; base; experimental study; eyelid conditioning; granule cell; improved; innovation; large scale simulation; mossy fiber; nervous system disorder; optogenetics; prevent; relating to nervous system; response; simulation; synergism; theories; time interval; treatment strategy

Project Summary/Abstract: One of the least understood computations in the brain is timing. We propose to combine large-scale simulations with eyelid conditioning experiments to reveal temporal coding mechanisms that underlie the cerebellum’s capacity for timing. The feasibility and power of this approach is facilitated by several related factors. Eyelid conditioning provides the ability to control cerebellar inputs and infer its output. Indeed, cerebellar timing is most clearly revealed in this way. This eyelid conditioning-cerebellum connection makes it possible to test large-scale cerebellar simulations in quantitative and biological relevant ways. There is also a natural synergy arising from combining simulations with experiments when each can be related with the other – simulation results suggest better experiments and interpretation of data, experiments inform simulations and make them more relevant and useful. The proposed studies are based on two relatively new discoveries about cerebellar connectivity: Golgi cells inhibit each other and deep cerebellar nucleus (DCN) neurons send collateral axons back to cerebellar cortex as mossy fibers. Preliminary data from simulations and experiments suggest these two connections confer the cerebellum with its capacity for timing and temporal coding. Simulations suggest specific predictions that can be tested with eyelid conditioning studies that include behavioral analysis, tetrode recordings and opto-genetic silencing of specific neurons. Results will inform more general theories of how neurons and synapses can implement temporal coding.

项目摘要/摘要：大脑中最不为人理解的计算之一是时间。我们建议 将大规模模拟与眼睑调节实验相结合，揭示时间编码机制 这是小脑计时能力的基础。这种方法的可行性和力量是由以下因素促进的 几个相关因素。眼睑调节提供了控制小脑输入并推断其输出的能力。 事实上，小脑计时以这种方式最清楚地揭示出来。这种眼睑调理-小脑连接 使得以定量和生物学相关的方式测试大规模小脑模拟成为可能。有 当模拟与实验都可以与实际相关时，这也是一种自然的协同作用 其他 – 模拟结果表明更好的实验和数据解释，实验为模拟提供信息 并使它们更具相关性和实用性。拟议的研究基于两个相对较新的发现 关于小脑连接：高尔基细胞相互抑制，小脑深部核 (DCN) 神经元发送信号 侧支轴突作为苔藓纤维返回小脑皮质。模拟和实验的初步数据 表明这两种连接赋予小脑计时和时间编码的能力。 模拟提出了具体的预测，可以通过眼睑调节研究进行测试，包括 行为分析、四极管记录和特定神经元的光遗传学沉默。结果将提供更多信息 神经元和突触如何实现时间编码的一般理论。