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对前庭信息和视觉/前庭互动的处理。最近的研究结果表明，小脑小结/悬垂(蚯蚓小叶X和IX、Nu)、前庭(VN)和小脑深部(CN)核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)歧义和区分重力和平移加速度所必需的多感觉汇聚。理论提出，GIA模糊性的解决方法是通过适当地将耳石、半规管和视觉感觉信息以及关于日常生活中最常见的线性加速统计的先验知识(概念化为贝叶斯先验知识)生成对重力的内部估计。在这里，我们计划探索这种内部模型在猕猴Nu Purkinje细胞(目标1和2)中的神经实现，并通过记录VN/CN(目标3)中的Nu投射神经元和Nu靶神经元，开始功能解剖这些信号是如何在VN-CN-Nu网络中产生的。我们将使用产生翻译错觉的刺激，而不实际传递任何翻译刺激来检验以下假设：(1)Nu Purkinje细胞活动代表了长期假设的重力和平移加速内部模型的输出；(2)重力和平移加速信号的神经关联都在Nu Purkinje细胞的不同群体中发现；(3)这两组Nu Purkinje细胞的群体活动是互补的，因此它们的净和等于GIA，正如理论预测的那样；(4)在稳态旋转过程中，可以使用视觉信号而不是管驱动信号来计算更可靠的重力估计，从而防止错误的倾斜和平移信号的产生；以及(5)只有顺向激活的Nu靶神经元才具有平移选择和重力选择反应特性，而反向激活的Nu投射神经元则不存在，所有这些神经元都是仅对通道激活(即对翻译没有反应)或GIA编码的细胞。总之，这些实验构成了必要的基础研究，以建立Nu-VN-CN电路作为惯性多感觉加工的关键区域，用于自我运动感知和空间定位，这对分心定位和惯性导航至关重要。一个 目前研究的主要创新是使用非自然刺激，这些刺激已知会导致倾斜和翻译错觉，以挑战系统并揭开潜在计算的面纱。这些实验将为长期假设的理论概念的神经关联提供新的定量证据，如内部模型和贝叶斯先验。因此，这项工作对于揭开小脑及其电路功能作用的复杂谜团具有重大而广泛的影响。

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.