NEURAL ORGANIZATION AND FUNCTION OF THE VESTIBULO-CEREBELLUM

前庭小脑的神经组织和功能

• 批准号: 7653561
• 负责人: Dora Angelaki
• 金额: $ 68.45万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7653561
• 关键词: Acceleration; Address; Animals; Area; Automobile Driving; Behavior; Behavioral; Bilateral; Brain Stem; Calibration; Cell Nucleus; Cells; Cerebellar Nuclei; Cerebellar vermis structure; Cerebellum; Chemicals; Clinical; Code; Cognitive deficits; Complex; Data; Detection; Discrimination; Disease; Eye Movements; Force of Gravity; Frequencies; Goals; Head; Knowledge; Lead; Lesion; Link; Lobule; Modeling; Monkeys; Motion; Motion Perception; Movement; Muscimol; Neurologic; Neurons; Nucleus fastigii; Parietal; Pathologic Nystagmus; Pattern; Perception; Probability; Process; Property; Purkinje Cells; Relative (related person); Reporting; Role; Rotation; Saccades; Semicircular canal structure; Signal Detection Analysis; Signal Transduction; Simulate; Space Perception; System; Systems Analysis; Techniques; Testing; Thalamic structure; Therapeutic; Translations; Vestibular nucleus structure; Vestibule; Visual; Visual Acuity; computerized data processing; information processing; multisensory; neurophysiology; optic flow; otoconia; public health relevance; relating to nervous system; research study; response; uvula; vestibulo-ocular reflex; virtual reality; visual-vestibular

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.

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，但对其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的小脑处理和皮质下视觉/前庭相互作用。所提出的目标是由惯性运动检测模型和最近的发现所激发的，即结节/悬雍垂浦肯野细胞反映了必要的耳管/耳石相互作用，这些相互作用是将净重力惯性加速度分离为重力和平移分量所必需的。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，并探索结节/悬雍垂浦肯野细胞的特性及其与前庭和顶核的连接。我们假设：（i）来自耳管/耳石汇聚的惯性前庭运动信号是在结节/悬雍垂皮质电路及其与前庭/小脑核的互连内计算的； (ii) 这些相同区域还实现了区分低频倾斜和平移所必需的视觉/前庭会聚； (iii) 浦肯野细胞的复杂尖峰活动携带系统校准所需的视觉翻译信号。此外，我们将解决反射性眼球运动和自我运动方向辨别任务期间头顶核的功能相关性。为了解决这些目标和假设，我们提出了一种使用多种技术的多方面方法，包括单单元记录、生理特征神经元的顺向/逆向识别、行为分析和化学灭活。总之，这些研究将为以下假设提供重要的检验：前庭和小脑核中的 NU 和 NU 目标神经元代表了自我运动感知和空间定向的惯性多感觉处理的主要通道。这些信号对于非中心定向和惯性导航至关重要。结果和结论对于理解通常伴随 NU 病变的空间定向缺陷非常重要。他们还将提供支持或反对皮层下神经活动和感知之间直接联系的第一个证据，并将弥合传统前庭系统分析和现代功能相关的相关分析技术之间的差距，这些技术将神经活动与动物的行为选择联系起来。公共卫生相关性：蚓部后部的前庭小脑及其与脑干核团的互连对于空间定向和运动检测至关重要。涉及这些区域的临床和实验性病变会导致临床眼球震颤、视力下降、姿势不稳定和空间定向丧失。中枢前庭疾病的神经学相关性仍然是一个谜，这给制定有效的治疗策略带来了主要障碍。这里提出的实验旨在填补知识上的一个非常显着的空白，这对于理解和治疗基本姿势和反射缺陷以及空间知觉的认知缺陷很重要。