Mechanisms of timing and temporal coding

项目摘要/摘要：大脑中最不被理解的计算之一是计时。我们建议 结合大规模模拟和眼皮条件作用实验，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威力是由以下方面促进的 几个相关因素。眼皮调节提供了控制小脑输入和推断其输出的能力。 事实上，小脑的时序以这种方式最清楚地揭示出来。这种眼皮调节-小脑联系 使以定量和生物相关的方式测试大规模小脑模拟成为可能。的确有 也是通过将模拟与实验相结合而产生的自然协同效应，当每个模拟与实验都可以与 其他-模拟结果建议更好的实验和数据解释，实验为模拟提供信息 并使它们更相关、更有用。拟议的研究基于两个相对较新的发现。 关于小脑连接：高尔基体细胞相互抑制，小脑深部核(DCN)神经元发出 侧支轴突作为苔藓纤维回到小脑皮质。来自模拟和实验的初步数据 认为这两个连接赋予小脑时间和时间编码的能力。 模拟提出了特定的预测，可以用眼皮调节研究进行测试，这些研究包括 行为分析、四极管录音和特定神经元的光遗传沉默。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。

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.