A Novel Model to Improve Neural Performance During Oxygen Deprivation
Abstract
The goal of this project is to understand how to prevent neurological dysfunction caused by low oxygen (hypoxia) in the brain. Brain hypoxia impairs cognitive and motor performance in pilots at altitude and is a leading cause of military air catastrophes. Further, hypoxic insults to the brain result in permanent disability and death in a host of clinical scenarios such as stroke and opioid overdose, which impact the lives of military personnel and civilians alike. Thus, novel strategies that improve the performance of neural function during hypoxia are urgently needed to ensure the safety of pilots and to offset damage caused hypoxia in clinical conditions. We hypothesize that improvements to three aspects of neuronal function that cause vulnerability during hypoxiaÑcellular metabolism, electrical signaling, and ion regulationÑ will lead to superior performance. To test this hypothesis, we use an innovative neural circuit that has the striking ability to naturally improve its function from zero activity during hypoxia to normal activity during hypoxia, a neural network in the brainstem of frogs. This model is unique because it provides direct insight into how groups of neurons can modify vulnerable biological processes to overcome hypoxic stress that disrupts brain performance in humans. Through three specific aims, we exploit this model to understand how circuits can transform multiple cellular and molecular components to resist hypoxia: (1) identify metabolic processes that maintain neural function during hypoxia, (2) determine mechanisms that promote healthy neuronal signaling during hypoxia, and (3) identify ion regulation mechanisms that contribute to hypoxia tolerance in neurons. These aims will be carried out with a cutting-edge technical approach that combines single-cell RNA sequencing, bioinformatics, patch clamp and circuit-level electrophysiology, and fluorescence imaging microscopy. Thus, the aims of this proposal will support an interdisciplinary training environment in neurobiology for the diverse undergraduate and graduate student population at the University of North Carolina-Greensboro. In sum, this work will lead to a novel Òbio-inspiredÓ approach that aims to engineer the human brain to improve performance during hypoxia.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 20, 2020
- Source ID
- W911NF2010275
Entities
People
- Joseph M Santin
Organizations
- Army Contracting Command
- Office of the Secretary of Defense
- University of North Carolina at Greensboro