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 Botzinger 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 inter neurons 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 inter-neurons 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.