Hypoglossal motor output is altered by C4 epidural electrical stimulation via ascending spinal and peripheral feedback pathways.

After cervical spinal cord injury (cSCI), upper airway dysfunction is highly prevalent, including a dramatically increased incidence of obstructive sleep apnea and swallowing dysfunction. While these deficits have often been attributed to secondary sources such as damage from complications of injury management or anatomical changes, there has recently been a greater appreciation for the modulatory role of spinal populations in upper airway behaviors that are disrupted by injury. Here, we illustrate in a rodent model of cSCI that epidural spinal stimulation (ESS) of the phrenic motor nucleus at spinal segment C4 alters motor output at the hypoglossal motor nucleus through activation of excitatory ascending spinal pathways and inhibitory peripheral sensory feedback mechanisms. These findings highlight the importance of spinal-brainstem communication in shaping the motor program of upper airway musculature and suggest that stimulation of the cervical spinal cord may be a viable therapeutic target for augmenting upper airway motor output after spinal injury.