NEURAL ORGANIZATION AND FUNCTION OF THE VESTIBULO-CEREBELLUM

描述(申请人提供)：中线前庭-小脑，由结节(蚯蚓小叶X)和悬垂(蚯蚓小叶IX)组成，长期以来一直与空间定位和视觉-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小脑对前庭信息的处理以及皮质下视觉/前庭的相互作用。拟议目标的动机是惯性运动探测模型和最近的研究结果，即小结/悬垂浦肯野细胞反映了必要的耳道/耳石相互作用，这是将净重力惯性加速度分离为重力和平移分量所必需的。本文拟进一步探讨前庭核、小脑核和小结/悬垂之间的信号处理，并探讨小结/悬垂浦肯野细胞的性质及其与前庭和顶核的联系。我们假设：(I)来自管/耳石会聚的惯性前庭运动信号是在小结/悬垂皮质回路及其与前庭/小脑核的相互连接中计算的；(Ii)这些相同区域也执行必要的视觉/前庭会聚，以区分低频下的倾斜和平移；以及(Iii)浦肯野细胞的复杂棘波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中，吻侧顶核的功能相关性。为了解决这些目标和假设，我们提出了一种多方面的方法，使用多种技术，包括单一单位记录，生理特征神经元的顺向/逆序识别，行为分析和化学失活。总之，这些研究将为前庭和小脑核团中的Nu和Nu靶神经元代表惯性多感觉加工的主要通道的假设提供一个至关重要的检验。这样的信号对同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将是重要的。它们还将提供支持或反对皮质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，这些分析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：前庭-小脑位于后蚯蚓，其与脑干核团的相互联系对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损害会导致临床眼球震颤、视力下降、姿势不稳定和空间定向力丧失。中枢性前庭疾病的神经学相关性仍然是一个谜，在确定有效的治疗策略方面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著的知识空白，这对理解和治疗基本姿势和反身性缺陷以及空间知觉的认知缺陷都很重要。

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.