NEURAL ORGANIZATION AND FUNCTION OF THE VESTIBULO-CEREBELLUM

描述（由申请人提供）：中线前庭-小脑由结节（蚓小叶X）和悬雍垂（蚓小叶IX）组成，长期以来一直与空间定向和视觉-前庭相互作用有关，但对潜在的神经生理学知之甚少。这些研究的长期目标是了解前庭信息和皮质下视觉/前庭相互作用的小脑处理。所提出的目标是出于惯性运动检测模型和最近的研究结果，结节/悬雍垂浦肯野细胞反映了必要的通道/耳石相互作用，是必要的分离净重力惯性加速度到重力和平移组件。在这里，我们建议进一步探讨前庭核，小脑核和结节/悬雍垂之间的信号处理，并探讨结节/悬雍垂浦肯野细胞的性质及其与前庭和顶核的连接。我们假设：（i）在结节/悬雍垂皮质电路及其与前庭/小脑核的互连内计算来自耳道/耳石会聚的惯性前庭运动信号;（ii）这些相同的区域还实现区分低频倾斜和平移所需的视觉/前庭会聚;以及（iii）浦肯野细胞的复杂尖峰活动携带系统校准所需的视觉平移信号。此外，我们将讨论在反射性眼球运动和自我运动方向辨别任务的喙顶核的功能相关性。为了解决这些目标和假设，我们提出了一个多方面的方法，使用多种技术，包括单单位记录，顺向/逆向识别的生理特征的神经元，行为分析和化学灭活。总之，这些研究将提供一个重要的测试的假设，即NU和NU-靶神经元在前庭和小脑核的惯性多感觉处理自我运动知觉和空间定向的主要管道。这些信号对于非同心定向和惯性导航至关重要。结果和结论将是重要的，在理解空间定向缺陷，通常伴随NU病变。他们还将提供第一个证据支持或反对皮层下神经活动和感知之间的直接联系，并将弥合传统的前庭系统分析和现代的，功能相关的，相关分析技术与动物的行为选择的神经活动之间的差距。公共卫生相关性：后蚓部的前庭小脑及其与脑干核团的相互连接对于空间定位和运动检测至关重要。涉及这些区域的临床和实验性病变导致临床眼球震颤和视力下降、姿势不稳定和空间定向丧失。中枢性前庭障碍的神经学相关性仍然是一个谜，在确定有效的治疗策略中构成了一个主要障碍。这里提出的实验旨在填补一个非常显着的知识空白，重要的理解和治疗基本的姿势和反射缺陷以及空间知觉的认知缺陷。

DESCRIPTION (provided by applicant): The midline vestibulo-cerebellum, consisting of the nodulus (vermis lobule X) and uvula (vermis lobule IX), has been long implicated in spatial orientation and visual-vestibular interactions but little is known about the underlying neurophysiology. The long-term goal of these studies is to understand the cerebellar processing of vestibular information and subcortical visual/vestibular interactions. The proposed aims are motivated by a model of inertial motion detection and recent findings that nodulus/uvula Purkinje cells reflect the necessary canal/otolith interactions that are necessary to separate net gravitoinertial acceleration into gravitational and translational components. Here we propose to further probe the signal processing between the vestibular nuclei, the cerebellar nuclei and the nodulus/uvula and to explore the properties of nodulus/uvula Purkinje cells and their connectivity with the vestibular and fastigial nuclei. We hypothesize: (i) that inertial vestibular motion signals from canal/otolith convergence are computed within the nodulus/uvula cortical circuitry and its interconnections with the vestibular/cerebellar nuclei; (ii) that these same areas also implement the visual/vestibular convergence necessary for distinguishing tilt and translation at low frequencies; and (iii) that complex spike activity of Purkinje cells carry visual translation signals needed for system calibration. In addition, we will address the functional relevance of the rostral fastigial nuclei during both reflexive eye movements and a self-motion direction discrimination task. To address these aims and hypotheses, we propose a multi-faceted approach using multiple techniques, including single unit recording, orthodromic/antidromic identification of physiologically-characterized neurons, behavioral analysis and chemical inactivation. Together, these studies will provide a vital test of the hypothesis that NU and NU-target neurons in the vestibular and cerebellar nuclei represent the main conduit of inertial multisensory processing for self-motion perception and spatial orientation. Such signals are vital for allocentric orientation and inertial navigation. Results and conclusions would be important in understanding spatial orientation deficits that typically accompany NU lesions. They will also provide the first evidence for or against a direct link between subcortical neural activities and perception and will bridge the gap between traditional vestibular system analysis and modern, functionally-relevant, correlation analysis techniques relating neural activities with animal's behavioral choices. PUBLIC HEALTH RELEVANCE: The vestibulo-cerebellum in the posterior vermis and its interconnections with brainstem nuclei are vital for spatial orientation and motion detection. Clinical and experimental lesions involving these areas lead to clinical nystagmus and reduced visual acuity, postural instability and loss of spatial orientation. Neurological correlates of central vestibular disorders are still a mystery, posing a major hurdle in defining effective therapeutic strategies. The experiments proposed here aim at filling a very notable gap in knowledge, important for understanding and treating both basic postural and reflexive deficits as well as cognitive deficits of spatial perception.