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Photo of Joseph Santin
Photo of Joseph Santin

Dr. Joseph Santin (Biology) received new funding from the Department of Defense for the project “A novel model to improve neural performance during oxygen deprivation.”

The goal of this project is to understand how to prevent neurological dysfunction caused by low oxygen (hypoxia) in the brain. Hypoxia impairs cognitive and motor performance in pilots at altitude and damages the brain in a host of health issues that impact the lives of military personnel and civilians alike. Brain hypoxia is now the leading cause of military air catastrophes, and the best-case scenario after an insult in clinical scenarios is often permanent disability and, at worst, premature death. When oxygen flow to the brain stops, neural performance fails which leads to pathological activity in neural networks.

A better understanding of how to improve the performance of neural circuits during hypoxia will be needed to improve motor function of pilots at altitude and offset damage caused by disrupted oxygen flow to the brain in clinical conditions. The researchers hypothesize that synergistic improvements in three aspects of neuronal function that cause vulnerability during energetic stress—cellular metabolism, electrical signaling, and ion regulation— will improve neuronal function during hypoxia.

To test this hypothesis, researchers use an innovative system that has the striking ability to improve its function from zero activity without O2 to normal activity without O2, a central pattern generating circuit in the brainstem of frogs. This model is attractive because it allows researchers to understand how the same group of neurons can modify vulnerable biological processes to transform their function to resist hypoxic stress that disrupts brain performance in humans.

Through three specific aims, researchers exploit this model to understand how circuits can alter multiple cellular and molecular components to overcome energetic insults: (1) identify metabolic processes that maintain network function during oxygen lack and simulated stroke, (2) determine mechanisms that promote healthy neuronal signaling during energetic stress, and (3) identify changes in ion channels that contribute to ion balance in stress-tolerant neurons.

These aims will be carried out with a cutting-edge technical approach that combines single-cell RNA sequencing, patch clamp and circuit-level electrophysiology, and fluorescence imaging microscopy. Thus, the aims of this proposal will support an integrative training environment in neurobiology to the diverse undergraduate and graduate student population at the UNCG. In sum, as the mechanisms underlying circuit function and metabolism are widely shared across vertebrate animals, our findings may inform how to reconfigure these conserved processes to eventually improve the performance of the human brain during hypoxia.

 
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