The computational importance of cerebellar processing

描述（由申请人提供）：小脑处理与一系列行为的准确表现有关，从感觉运动转换到执行控制。考虑到这种广泛的范围，在小脑微电路的组织和小脑区域与其他大脑区域连接的闭环方式方面，存在着不同形态和物种的显著一致性。这种一致性表明了一个共同的计算角色，我们假设最通常被描述为自适应时间滤波器。为了验证这一假设，我们将研究小脑在简单运动可塑性、学习固定稳定性方面的功能。在这种情况下，作为自适应滤波器的处理应该被实现为小脑中的一种能力，可以替代地充当比例增益、积分增益或微分增益元件。在Aim 1中，将通过在斑马鱼幼虫中使用双光子钙成像来评估小脑过滤，以测量输入颗粒和输出浦肯野细胞群的活动。过滤器的适应性将通过测量输入和输出神经元之间关系的变化来确定，因为固定物被训练成更大或更小的稳定性。在Aim 2中，将构建小脑的计算模型，生成实验测量的信号变换，并对小脑滤波的机制进行预测。这些预测将通过颗粒细胞的局部刺激和由此产生的浦肯野神经元反应的测量来验证。这些数据合在一起，有望对小脑在行为中的计算重要性产生迄今为止最完整的理解。

DESCRIPTION (provided by applicant): Cerebellar processing is associated with the accurate performance of a range of behaviors, from sensorimotor transformations to executive control. Given this wide range, there is remarkable consistency across modality and species in the organization of cerebellar microcircuitry and the closed-loop manner with which cerebellar regions are connected to other brain areas. This consistency suggests a common computational role, which we hypothesize is most generally described as an adaptive temporal filter. To test this hypothesis, we will investigate cerebellar function in a simple motor plasticity, the learning of fixation stability. In this setting, processing as an adaptive filter should be realized as a capacity in the cerebellum to alternatively act as a proportional, integrating, or differentiating gain element. In Aim 1, cerebellar filtering will be assessed by using two-photon calcium imaging in the larval zebrafish to measure activity at both input granule and output Purkinje cells populations. Adaptation of the filter will be determined by measuring changes in the relationship between input and output neurons as fixations are trained toward greater or lesser stability. In Aim 2, computational models of the cerebellum will be constructed that generate the experimentally measured signal transformation and make predictions about the mechanisms of cerebellar filtering. These predictions will be tested by focal stimulation of granule cells and measurement of resultant Purkinje neuron responses. Together these data promise to generate the most complete understanding to date of the cerebellum's computational importance in behavior. PUBLIC HEALTH RELEVANCE: The cerebellum contains almost half of all neurons in the brain, yet we don't have clear understanding what the cerebellum does. In this project we will determine how information is processed in the cerebellum by recording from the majority of cerebellar neurons during behavior. These results will lay the groundwork necessary to develop treatments for diseases of cerebellar function, including spino-cerebellar ataxia, dyslexia, and autism.