Stimulating V2a Neurons Improves Breathing in Mice After Spinal Cord Injury

Research By: Victoria Jensen, PhD | Steven Crone, PhD

Post Date: March 5, 2024 | Publish Date: March 5, 2024

Neurosurgery | Top Scientific Achievement

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High-level spinal cord injuries disrupt connections between the brainstem and respiratory motor neurons in the spinal cord, which can severely impair the ability to breathe. When such injuries occur, mechanical ventilation and diaphragm pacing is typically required.

In this study, a research team led by first author Victoria Jensen, PhD, and corresponding author Steven Crone, PhD, demonstrates that V2a neurons, which are not required for breathing in healthy rodents at rest, play a crucial role in the recovery of breathing following injury. In fact, increasing the excitability of V2a neurons restores bursting activity to a previously paralyzed diaphragm within hours, days or weeks following injury.

“Our findings suggest that therapies to alter the excitability of V2a neurons could significantly improve breathing following spinal cord injury,” Crone says. “The data also indicate that therapies targeting V2a neurons would be most beneficial during the early stages of recovery or in severe injuries, but would likely be less effective if robust inspiratory activity has already been achieved.”

Pinning down the unexpected role of V2a neurons required Jensen to become skilled at performing electromyography (EMG) recordings of the diaphragm in transgenic mouse models in which it is possible to alter the firing activity of V2a neurons. This form of measurement is now an established technique in the Crone lab.

Future experiments will use surgically implanted radio transmitters to measure recovery of diaphragm function over time while V2a neurons are chronically activated. In addition, the Crone lab is investigating a variety of alternative methods that could potentially activate V2a neurons in humans after injury, including identifying drugs that target molecules expressed by V2a neurons and developing novel electrical stimulation methods to target spinal neurons.

Cincinnati Children’s co-authors included Sarah Baumgartner and Ian Walling. Collaborators also included experts with the University of Kentucky and Texas A&M University.