Brainstem network controlling descending drive to phrenic motoneurons in rat

Abstract

Contraction of the diaphragm is controlled by phrenic motoneurons that receive input from sources that are not fully established. Bulbospinal (second-order) neurons projecting to phrenic motoneurons and propriobulbar (third-order) neurons projecting to these bulbspinal neurons were investigated in rat by transsynaptic transport of the neuroinvasive pseudorabies virus. Bulbospinal neurons were located predominantly in the medullary lateral tegmental field in two functionally described regions, the ventral respiratory group and Bötzinger complex. An intervening region, the pre-Bötzinger complex, contained essentially no phrenic premotoneurons. Bulbospinal neurons were also located in ventral, interstitial, and ventrolateral subnuclei of the solitary tract, and gigantocellular, Kölliker-Fuse, parabrachial, and medullary raphe nuclei. A monosynaptic pathway to phrenic motoneurons from the nucleus of the solitary tract was confirmed; monosynaptic pathways from upper cervical spinal cord, spinal trigeminal nucleus, medical and lateral vestibular nuclei, and medial pontine tegmentum were not verified. Locations of third-order neurons were consistent with described projections to the ventral respiratory group, from contralateral ventral respiratory group, Bötzinger complex, A5 noradrenergic cell group, and the following nuclei; solitary, raphe, Kölliker-Fuse, parabrachial, retrotrapezoid, and paragigantocellular. Novel findings included a projection from locus coeruleus to respiratory premotoneurons and the lack of previously described pathways from area postrema and spinal trigeminal nucleus. These second- and third-order neurons from the output network for diphragm motor control which includes numerous behaviors (e.g., respiration, phonation, defecation). Of the premotoneurons, the rostral ventral respiratory group is the primary population controlling phrenic motoneurons.