Motor, Vestibular, and Mnemonic Interactions in Directional Heading Perceptions

描述（由申请人提供）：一种通常被认为是理所当然的认知功能是在环境中移动时保持方向感和位置感的能力。这种意识对于在世界上正常活动和运作至关重要。当我们的空间定向感受到中枢神经系统或前庭疾病的损害时，这种疾病的严重性和破坏性对患者和临床医生来说都是显而易见的。常见的问题包括头晕、平衡和空间定向障碍。为了开发有效的治疗方法，我们需要了解空间定向的神经过程，以及这些过程中出现的错误导致定向障碍。因此，这项建议的长期目标是更好地了解有助于空间感知的神经机制。使用动物模型和电生理技术，我们将记录从一类神经元在大鼠编码的动物的定向标题在allocentric坐标。这些神经元被称为“头部方向（HD）细胞”，并已在非人类灵长类动物中鉴定。我们的目的是了解头部方向细胞如何在各种条件下，涉及到空间定位和定向障碍的问题。实验研究1）HD细胞在三维中的响应-特别是，当动物在执行空间记忆任务时倒置和倒置运动时它们如何响应，2）前庭系统（半圆管和耳石器官两者）在产生HD细胞响应中的作用，3）运动/本体感受线索在头部角速度细胞放电中的作用，4）边缘系统电路在纹状体中产生头部方向细胞反应中的作用，以及5）在定向障碍期间HD细胞的反应。总之，我们获得的结果将提供必要的信息，了解空间定向障碍的神经生理学基础，并加强我们的理解空间信息是如何组织和处理在哺乳动物的大脑。这些实验的结果将为理解空间定向的基本神经机制提供关键信息。最终，我们希望对定向障碍有更好的神经生理学理解，并利用这些信息来开发有效的治疗空间障碍的方法，如眩晕，晕动病，导航障碍。此外，对于患有前庭障碍的患者、老年患者和患有阿尔茨海默病（通常与边缘系统结构中的显著病理学相关的疾病）的患者来说，经历空间定向障碍到需要持续监督的程度是常见的。了解空间信息在大鼠大脑中的处理方式将为人类空间过程的复杂性提供线索。

DESCRIPTION (provided by applicant): One cognitive function often taken for granted is the ability to maintain a sense of direction and location while moving about in the environment. This awareness is essential for getting around and functioning normally in the world. When our sense of spatial orientation is compromised by central nervous system or vestibular disease, the seriousness and devastation of the disorder becomes readily apparent both to the patient and clinician. Common problems include dizziness, balance, and spatial disorientation. To develop effective treatments for these disorders, we will need to understand the neural processes underlying spatial orientation and what goes awry with these processes that brings about disorientation. Thus, the long-term goal of this proposal is to better understand the neural mechanisms contributing to spatial perception of one's orientation. Using an animal model and electrophysiological techniques we will record from a class of neurons in rats that encodes the animal's directional heading in allocentric coordinates. These neurons are referred to as 'head direction (HD) cells' and have been identified in non-human primates. Our aim is to understand how head direction cells respond under a variety of conditions that pertain to issues of spatial orientation and disorientation. The experiments investigate 1) the response of HD cells in three dimensions - in particular, how they respond when the animal is inverted and locomotes upside-down while performing a spatial memory task, 2) the role of the vestibular system, both the semi-circular canals and the otolith organs, in generating HD cell responses, 3) the role of motor/proprioceptive cues in the discharge of angular head velocity cells, 4) the role of limbic system circuitry in generating head direction cell responses in the striatum, and 5) the response of HD cells during periods of disorientation. In sum, the results we obtain will provide essential information for understanding the neurophysiological basis for spatial orientation disorientation, and enhance our understanding of how spatial information is organized and processed in the mammalian brain. PUBLIC HEALTH RELEVANCE The results from these experiments will provide key information in understanding the basic neural mechanisms underlying spatial orientation. Ultimately, we would like to develop a better neurophysiological understanding of disorientation and use this information to develop effective treatments for spatial disorders such as vertigo, motion sickness, navigational disorders. Further, it is common for patients with vestibular disorders, elderly patients, and patients with Alzheimer's disease, a disease often associated with marked pathology in limbic system structures, to experience spatial disorientation to the extent that constant supervision is required. Learning how spatial information is processed in the rat brain will provide clues about the complex nature of spatial processes in humans.