Detangling spinal respiratory network responses to cervical epidural stimulation after spinal cord injury

Respiratory insufficiency is the leading cause of mortality after spinal cord injury, yet current pacing strategies override brainstem rhythm generators, limiting adaptability and rehabilitation. Electrical stimulation of the spinal cord in the locomotor system enables volitional patterned movements after injury by activating spinal central pattern generators. However, as the central pattern generators for breathing lie in the brainstem, it is unclear what neural populations are acted upon when rhythmic bursting is reanimated by electrical stimulation of the cervical spinal cord after injury.

Here, in anesthetized rats with cervical injury, we show that inspiratory-triggered, expiratory-triggered, and tonic stimulation all elicit diaphragm motor output, but descending inputs and spinal inhibition are necessary to achieve appropriate endogenous respiratory patterning. Short-latency responses and increasing immediate early gene expression indicate recruitment of local spinal interneurons, including inhibitory populations. This furthers our understanding of the respiratory neural populations epidural stimulation interacts with and highlights the necessity of inspiratory-patterned stimulation.

We would like to thank Dr. David Baekey for technical help and fruitful, intellectual discussions regarding this study. We would also like to thank the animal care staff, veterinarians, and administrative support in the University of Florida Animal Care Services Division.

Finally, we are grateful for the robust and supportive scientific environment created by the Breathing Research and Therapeutics Center. This work was supported by funding from National Institute of Health grant numbers R01HL153102 (to EAD), T32HL134621 (to GSM/AM), and F31HL174079 (to ARM Department of Neuroscience, University of Florida, Gainesville, FL, USA Alyssa R. Mickle, Jesús Peñaloza-Aponte & Erica A.

Dale Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, USA McKnight Brain Institute, University of Florida, Gainesville, FL, USA Department of Physiology and Aging, University of Florida, Gainesville, FL, USA The authors declare no competing interests Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.

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