Neural organization and function of the vestibulo-cerebellum

描述（由申请人提供）：这些研究的长期目标是了解小脑处理前庭信息和视觉/前庭相互作用。最近的研究发现，小脑结节/小腭（小叶X和IX， NU）、前庭核（VN）和小脑深部核（CN）似乎形成了一个相互连接的网络，实现了解决重力-惯性加速度（GIA）模糊和区分重力与平移加速度所必需的多感觉收敛。理论已经提出，通过适当地“结合”耳石，半规管和视觉感官信息，以及关于日常生活中最常见的线性加速度统计的先验知识（概念化为贝叶斯先验），通过生成重力的内部估计来解决GIA歧义。在这里，我们计划在猕猴NU浦肯野细胞中探索这种内部模型的神经实现（目标1和2），并通过记录VN/CN中的NU-投射和NU-靶神经元，开始对VN-CN- NU网络中如何产生这些信号进行功能解剖（目标3）。我们将使用产生翻译错觉的刺激，而不实际提供任何翻译刺激来测试以下假设：(1)NU浦肯野细胞活性代表了长期假设的重力和平移加速度内部模型的输出；(2)在不同的NU浦肯野细胞群中均发现了重力和平移加速度信号的神经相关因子；(3)这两组NU浦肯野细胞的种群活力是互补的，其净和等于理论预测的GIA；(4)视觉可以代替运河驱动信号，在稳态旋转时计算更可靠的重力估计，从而防止产生错误的倾斜和平移信号；(5)翻译选择性和重力选择性反应特性只存在于正侧激活的nu -靶神经元中，而不存在于反侧激活的nu -投射神经元中，它们要么是仅管（即对翻译没有反应），要么是gia编码细胞。总之，这些实验构成了建立NU-VN-CN电路作为自运动感知和空间定向的惯性多感官处理的关键领域所必需的基础研究，这对非同心定向和惯性导航至关重要。一个

DESCRIPTION (provided by applicant): The long-term goal of these studies is to understand the cerebellar processing of vestibular information and visual/vestibular interactions. The proposed studies are motivated by recent findings that the cerebellar nodulus/uvula (vermis lobules X and IX, NU), the vestibular (VN) and deep cerebellar (CN) nuclei appear to form an interconnected network that implements multisensory convergence necessary to resolve the gravito- inertial acceleration (GIA) ambiguity and distinguish gravity from translational accelerations. Theory has proposed that the GIA ambiguity is resolved by generating an internal estimate of gravity by appropriately 'combining' otolith, semicircular canal and visual sensory information, as well as prior knowledge about the statistics of linear accelerations experienced most commonly in everyday life (conceptualized as a Bayesian prior). Here we plan to probe the neural implementation of such an internal model in macaque NU Purkinje cells (aims 1 & 2), as well as start a functional dissection of how these signals are generated within the VN-CN- NU network by recording from NU-projecting and NU-target neurons in the VN/CN (aim 3). We will use stimuli that create the illusion of translation, without actually delivering any translation stimulus to test the following hypotheses: (1) NU Purkinje cell activity represents the output of long-postulated internal models for gravity and translational acceleration; (2) Neural correlates of gravity and translational acceleration signals are both found in distinct populations of NU Purkinje cells; (3) Population activity of these two groups of NU Purkinje cells are complementary to each other, such that their net sum equals GIA, as predicted by theory; (4) Vision can be used, instead of canal-driven signals, to compute a more reliable estimate of gravity during steady-state rotation, thus preventing the generation of erroneous tilt and translation signals; and (5) Translation-selective and gravity-selective response properties are only found in orthodromically-activated NU-target neurons, but not antidromically-activated NU-projecting neurons, all of which are either canal-only (i.e., have no response to translation) or GIA-coding cells. Together, these experiments constitute fundamental studies necessary to establish the NU-VN-CN circuitry as key areas in inertial multisensory processing for self-motion perception and spatial orientation, critical for allocentric orientation and inertial navigation. A major innovation in the current studies is the use of un-natural stimuli that are known to induce tilt and translation illusions to challenge the system and unmask the underlying computations. These experiments will provide novel quantitative evidence for the neural correlates of long-postulated theoretical concepts, like internal models and Bayesian priors. Thus, this work has a significant broader impact for unveiling the intricate mysteries of the functional roles of the cerebellum and its circuitry.