Motor, Vestibular, and Mnemonic Interactions in Directional Heading Perceptions

描述（由申请人提供）：一种经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的能力。这种意识对于在这个世界上四处走动和正常运作是必不可少的。当我们的空间方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这些疾病的方法，我们需要了解空间定向的神经过程，以及这些过程出了什么问题导致了定向障碍。因此，这项建议的长期目标是更好地理解有助于一个人的方向的空间感知的神经机制。利用动物模型和电生理技术，我们将记录大鼠的一类神经元，这些神经元在异心坐标中编码动物的方向方向。这些神经元被称为“头部方向（HD）细胞”，已经在非人类灵长类动物中发现。我们的目的是了解头部方向细胞在与空间定向和定向障碍有关的各种条件下的反应。实验研究了1)HD细胞在三维空间上的反应，特别是当动物在执行空间记忆任务时倒立和倒立运动时它们是如何反应的；2)前庭系统，包括半圆形管道和耳石器官，在产生HD细胞反应中的作用；3)运动/本体感觉线索在角头速度细胞放电中的作用。4)边缘系统回路在纹状体中产生头向细胞反应中的作用，以及5)HD细胞在定向障碍时期的反应。总之，我们获得的结果将为理解空间定向障碍的神经生理学基础提供重要信息，并增强我们对哺乳动物大脑中空间信息的组织和处理方式的理解。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一个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，如眩晕、晕动病、导航障碍。此外，前庭功能障碍患者、老年患者和阿尔茨海默病患者（阿尔茨海默病患者通常与边缘系统结构的明显病理相关）通常会经历空间定向障碍，以至于需要持续的监督。了解空间信息在大鼠大脑中是如何处理的，将为了解人类空间处理的复杂本质提供线索。

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.