Quantitative re-evaluation of descending serotonergic and non-serotonergic projections from the medulla of the rodent: evidence for extensive co-existence of serotonin and peptides in the same spinally projecting neurons, but not from the nucleus raphe magnus.

A quantitative analysis of serotonin (5-HT) and spinally-projecting neurons was re-evaluated in the rodent. The findings indicate that most (nearly 90%) of the medullary 5-HT neurons projected to the lumbar spinal cord, and most (up to 85%) of the spinally projecting neurons within the distribution of the serotonergic neurons contained 5-HT immunoreactivity. However, in nucleus raphe magnus (NRM) only about two-thirds of the projection cells were 5-HT immunoreactive. These data support two general conclusions: (1) the raphe-spinal system consists primarily of an extensive 5-HT pathway with neuronal subsets containing the co-localized peptides. Only the NRM contains a major non-5-HT projection. (2) As most of the medullary 5-HT neurons project to the caudal spinal segments of the rodent, collateralization of individual 5-HT neurons is extensive and widespread, existing to different spinal cord levels, as well as to other medullary nuclei, e.g., cranial nerve and inferior olivary nuclei. These findings argue that although differences are present within the 5-HT distributions, the raphe-spinal system as a whole should be considered to be a relatively homogeneous pathway containing 5-HT as the common element rather than as separate populations containing major projections of 5-HT alone, 5-HT co-localized with peptides and peptides without 5-HT.