Detangling the spinal respiratory network’s 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 by electrical stimulation of the cervical spinal cord. In anesthetized rats with cervical injury, we compared inspiratory-triggered, expiratory-triggered, and open-loop stimulation under varying descending inputs. All stimulation patterns elicit diaphragm motor output, but descending inputs and spinal inhibition are necessary to achieve appropriate endogenous respiratory patterning. Short-latency responses and increased immediate early gene expression indicated 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.