NEURAL ORGANIZATION AND FUNCTION OF THE VESTIBULO-CEREBELLUM

前庭小脑的神经组织和功能

• 批准号: 8063904
• 负责人: Dora Angelaki
• 金额: $ 67.45万
• 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 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063904
• 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; Health; 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; 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）：中线前沿 - 脑，由Nodulus（Vermis Lobule X）和Uvula（Vermis Lobule IX）组成，长期以来一直与空间取向和视觉vestibular相互作用有关，但知之甚少。这些研究的长期目标是了解前庭信息和皮层视觉/前庭相互作用的小脑处理。提出的目标是由惯性运动检测模型和最新发现，即Nodulus/Uvula Purkinje细胞反映了必要的运河/耳石相互作用，这些相互作用是将净净引力加速分解为重力和翻译成分所必需的。在这里，我们建议进一步探测前庭核，小脑核和nodulus/uvula之间的信号加工，并探索Nodulus/Uvula Purkinje细胞的性质及其与前庭和fastibial核的连通性。我们假设：（i）在Nodulus/Uvula皮质电路中计算出来自运河/耳石收敛的惯性前庭运动信号及其与前庭/小脑核的互连； （ii）这些相同区域还实施了以低频区分倾斜和翻译所需的视觉/前庭收敛； （iii）Purkinje细胞的复杂尖峰活性具有系统校准所需的视觉翻译信号。此外，我们将在反射性眼动和自我运动方向歧视任务中介绍鼻孔固有核的功能相关性。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，包括单位记录，对生理特征的神经元的正质/抗肿瘤鉴定，行为分析和化学灭活。总之，这些研究将为假说提供至关重要的检验，即前庭和小脑核中的NU和NU-TARGET神经元代表了惯性多感官处理以进行自我运动感知和空间取向的主要渠道。此类信号对于同类方向和惯性导航至关重要。结果和结论对于理解通常伴随NU病变的空间取向缺陷很重要。他们还将为皮层神经活动与感知之间的直接联系提供第一个证据，并将弥合传统前庭系统分析与现代功能相关的，相关分析技术与动物行为选择有关的差距。公共卫生相关性：后vermis中的前庭脑及其与脑干核的互连对于空间取向和运动检测至关重要。涉及这些区域的临床和实验病变导致临床眼球震颤，并降低视力，姿势不稳定和空间取向的丧失。中央前庭疾病的神经相关性仍然是一个谜，在定义有效的治疗策略方面构成了一个重大障碍。这里提出的实验旨在填补知识的非常明显的差距，对于理解和治疗基本的姿势和反思性缺陷以及空间感知的认知缺陷很重要。