Otolith-Dependent Cognition in Mice

描述(申请人提供)：准确的导航被认为依赖于定向的神经表示，定向由遍布边缘系统的头部方向细胞的上升电路携带。这种头部方向信号似乎严重依赖于前庭系统，因为前庭损伤会扰乱头部方向信号和导航能力。然而，前庭损伤也会扰乱其他大脑信号，如海马区的Place细胞信号，因此这种侧枝损伤可能会导致导航障碍。作为补充，拟议的研究将使用耳石缺陷小鼠，这些小鼠的头部方向信号已经退化，以评估头部方向信号在里程碑式导航和路径整合中的作用。这项拟议的研究将为前庭信号在空间神经表征中的作用以及这些表征在导航中的作用提供重要的见解。彻底了解前庭对空间的神经和认知表征的贡献可能会为前庭病理的治疗提供新的方法。 与公共卫生相关：定向障碍可发生在许多病理中，包括痴呆症、阿尔茨海默病和药物滥用等。了解导致定向障碍的大脑机制将提高我们治疗或预防这些疾病的这一衰弱部分的能力。

DESCRIPTION (provided by applicant): Accurate navigation is thought to depend on a neural representation of directional heading, which is carried by an ascending circuit of head direction cells located throughout the limbic system. This head direction signal appears to depend critically on the vestibular system, as the head direction signal and navigation abilities are disrupted by vestibular damage. However, vestibular lesions also disrupt other brain signals, such as the place cell signal of hippocampus, and navigation deficits may therefore result from this collateral damage. As a complementary approach, the proposed studies will use otoconia-deficient mice, which have degraded head direction signals, to evaluate the role of the head direction signal in landmark navigation and path integration. The proposed studies will provide important insight into the roles of vestibular signals in neural representations of space and the roles of these representations in navigation. A thorough understanding of the vestibular contribution to the neural and cognitive representations of space may allow new approaches to the treatment of vestibular pathologies. PUBLIC HEALTH RELEVANCE: Disorientation can occur in many pathologies, including dementia, Alzheimer's disease, and drug abuse, among others. Understanding the brain mechanisms that contribute to disorientation will advance our ability to treat or prevent this debilitating component of these disorders.