Ryan M. Yoder, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): The present proposal is an important step in discovering the neural mechanisms underlying spatial navigation, which requires continual updating of an individual's body position and movements relative to the location of a desired goal. The head direction (HD) signal, which includes spatial landmark and self- movement information, is thought to be the neural representation of an individual's direction. The network of brain structures involved in HD signal generation and control have been discovered in previous studies but the nature of information contributed by each brain structure remains unclear. The proposed experiments are designed to assess several key aspects of the HD signal, including: 1) the contribution of the postsubiculum (PoS) to the HD signal: 2) the type(s) of vestibular information included in the HD signal; and 3) the mechanism responsible for disruption of the HD signal during inverted locomotion. Specifically, HD activity will be assessed in rats following PoS lesion; HD activity will be assessed in mice lacking gravireceptors during upright and inverted locomotion. Results will provide a greater understanding of the HD signal's information content and may enable more effective treatments for disorders related to vestibular dysfunction. [unreadable] [unreadable] [unreadable]

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.

? DESCRIPTION (provided by applicant): Accurate navigation is thought to depend on neural representations of location and directional heading, which are carried by head direction cells, place cells, and grid cells. Head direction cells depend more heavily [than place cells] on signals from the otolith organs, but no studies have investigated the otolithic contribution to grid cell activity. Spatial deficits associated with otolith dysfunction may therefore result from disrupted head direction and/or grid cell activity. The proposed studies will test the otolithic contributionto entorhinal cortical grid cell activity during visual and non-visual navigation tasks. Results will provide important insight into the roles of vestibular information in neural representations of space, and the roles of these representations in navigation. A thorough understanding of the vestibular contribution to neural representations of space may enable new treatment approaches for cognitive deficits resulting from vestibular pathology.