Botzinger neurons project towards bulbospinal neurons in the rostral ventrolateral medulla of the rat

Sympathetic nerve activity often fluctuates with the respiratory cycle, but the central neurons that impose this respiratory modulation have not been conclusively identified. In the present study, we used intracellular recording and dye-filling to identify expiratory neurons in the Botzinger complex. Our aim was to see if Botzinger neurons project towards putative cardiovascular neurons in the rostral ventrolateral medulla. In the first series of experiments, histochemistry and immunohistochemistry were used to reveal the labelled Botzinger neurons and neurons immunoreactive for tyrosine hydroxylase. Two out of four Botzinger neurons had axon varicosities that were closely apposed to tyrosine hydroxylase-immunoreactive neurons with cell bodies located within 0.6 mm caudal to the facial nucleus (three and five close appositions, respectively). In a second series of studies, rats were injected with cholera toxin B into the intermediolateral cell column of the spinal cord 4-7 days before the electrophysiological recording. Eight of the fourteen labelled Botzinger neurons had a direct projection towards cholera toxin B-labelled neurons in the rostral ventrolateral medulla. Close appositions were found on both somata and proximal dendrites (5 ± 2 close appositions/neuron, n = 8). The present study supports the idea that a direct projection from Botzinger neurons to presympathetic neurons in the rostral medulla plays a role in the respiratory modulation of sympathetic nerve activity.