# Acquiring resistance to anoxia in neural circuit function

> **NIH NIH R15** · UNIVERSITY OF NORTH CAROLINA GREENSBORO · 2020 · $354,603

## Abstract

Abstract
The goal of this project is to understand how to prevent neurological dysfunction caused by metabolic
stress in the brain. Metabolic stress triggered by impaired oxygen delivery is well known to damage
the brain in devastating health issues such as stroke, opioid overdose, and traumatic brain injury. The
best case scenario after an insult is often permanent disability and, at worst, premature death. When
oxygen flow to the brain stops in these conditions, normal neuronal function fails which leads to
pathological activity in neural networks. We hypothesize that synergistic improvements in three
aspects of neuronal function that cause vulnerability during energetic stress—cellular metabolism,
electrical signaling, and ion regulation— will lead to a state of neuroprotection. To test this
hypothesis, we use a model circuit with a dramatic ability to shift between states of very low and very
high tolerance to energetic stress as a part of adult life, a central pattern generating circuit in the
brainstem of frogs. This model is attractive because it allows us to understand how the same group of
neurons can modify vulnerable biological processes to transform their function to resist energetic
insults that damage the brain in human diseases. We will test our hypothesis with three specific aims:
(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 an integrative technical approach that includes high-throughput
single-cell molecular biology, patch clamp and circuit-level electrophysiology, and fluorescence
imaging microscopy. Thus, the aims of this AREA (R15) proposal will afford diverse training
opportunities to undergraduate and graduate students. In sum, as the mechanisms underlying circuit
function and metabolism are widely shared across vertebrate animals, we expect our findings to build
a framework that informs how to improve neural function during energetic stress in the mammalian
brain.

## Key facts

- **NIH application ID:** 9965323
- **Project number:** 1R15NS112920-01A1
- **Recipient organization:** UNIVERSITY OF NORTH CAROLINA GREENSBORO
- **Principal Investigator:** Ayalew Ligaba Osena
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,603
- **Award type:** 1
- **Project period:** 2020-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965323

## Citation

> US National Institutes of Health, RePORTER application 9965323, Acquiring resistance to anoxia in neural circuit function (1R15NS112920-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965323. Licensed CC0.

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