Postnatal development of brainstem serotonin-containing neurons projecting to lumbar spinal cord in rats

We quantified postnatal changes in brainstem serotonin (5-hydroxytryptamine, 5-HT)-containing neurons projecting to lumbar spinal cord. The medulla-spinal cord descending neurons were identified by a retrograde neurotracer, choleratoxin B subunit (CTb), and 5-HT neurons were stained by immunohistochemistry. Double-labeled neurons were assumed to be 5-HT neurons projecting to the lumbar spinal cord, and were quantitatively analyzed in each raphe nucleus in the medulla. The following results were obtained: (1) At PND 3, numerous CTb-labeled neurons (CTLN) were already present in the raphe pallidus (B1), while few CTLN were seen in raphe obscurus (B2) and raphe magnus (B3). CTLN then rapidly increased in number and were separately distributed after PND 7 in B3 and after PND 14 in B2. (2) At PND 3, numerous 5-HT-containing neurons were already present in B1–B3, with 23.4% and 14.0% of them labeled with CTb in B1 and B2, respectively, while there were few double-labeled neurons in B3. From PND 3 to 28, although the proportion of double-labeled to 5-HT neurons remained unchanged in B1 and B2, that in B3 rapidly increased from 5.8% at PND 7 to 28.8% at PND 14. Previous studies have shown that the 5-HT neurons in B3 send fibers mainly to the dorsal horn, while those in B1 and B2 send fibers mainly to the ventral horn at all spinal cord levels. Taken together, the present findings suggest that the brainstem 5-HT systems influence the ventral horn of the spinal cord, where spinal motoneurons exist earlier than in the dorsal horn. The functional significance of these early 5-HT systems in motor development and/or disabilities is discussed.