Dorsal and ventral aspects of the most caudal medullary reticular formation have differential roles in modulation and formation of the respiratory motor pattern in rat

The respiratory pattern generator of mammals is anatomically organized in lateral respiratory columns (LRCs) within the brainstem. LRC compartments serve specific functions in respiratory pattern and rhythm generation. While the caudal medullary reticular formation (cMRF) has respiratory functions reportedly related to the mediation of expulsive respiratory reflexes, it remains unclear whether neurons of the cMRF functionally belong to the LRC. In the present study we specifically investigated the respiratory functions of the cMRF. Tract tracing shows that the cMRF has substantial connectivity with key compartments of the LRC, particularly the parafacial respiratory group and the Kölliker-Fuse nuclei. These neurons have a loose topography and are located in the ventral and dorsal cMRF. Systematic mapping of the cMRF with glutamate stimulation revealed potent respiratory modulation of the respiratory motor pattern from both dorsal and ventral injection sites. Pharmacological inhibition of the cMRF with the GABA-receptor agonist isoguvacine produced significant and robust changes to the baseline respiratory motor pattern (decreased laryngeal post-inspiratory and abdominal expiratory motor activity, delayed inspiratory off-switch and increased respiratory frequency) after dorsal cMRF injection, while ventral injections had no effect. The present data indicate that the ventral cMRF is not an integral part of the respiratory pattern generator and merely serves as a relay for sensory and/or higher command-related modulation of respiration. On the contrary, the dorsal aspect of the cMRF clearly has a functional role in respiratory pattern formation. These findings revive the largely abandoned concept of a dorsal respiratory group that contributes to the generation of the respiratory motor pattern.