Pre-phrenic interneurons: Characterization and role in phrenic pattern formation and respiratory recovery following spinal cord injury

The phrenic motor system receives excitatory inspiratory bulbospinal drive from inspiratory pre-motor neurons in the rostral ventral respiratory group and descending inhibition from bulbospinal Bötzinger complex units in the brainstem. While phrenic motoneurons have been extensively studied, a thorough understanding of the role of pre-phrenic interneurons in respiratory pattern formation is only beginning to emerge. Pre-phrenic interneurons are located at upper cervical spinal cord levels, as well as within and around the phrenic nucleus at mid-cervical levels. We speculate they may be involved in polysynaptic bulbospinal relays to phrenic motoneurons and/or may operate independently to modulate respiratory motor outputs. Additionally, pre-phrenic interneurons may serve as a neuroanatomic substrate for a putative spinal respiratory rhythm/pattern generator. Lastly, pre-phrenic interneurons also appear to play an important role in respiratory recovery following spinal cord injury. These various roles subserved by pre-phrenic interneurons are reviewed and discussed.