Anatomic relationships of the human nucleus paragigantocellularis lateralis: a DiI labeling study

The nucleus paragigantocellularis lateralis (PGL) is located in the rostral ventrolateral medulla (RVLM), a brainstem region that regulates homeostatic functions, such as blood pressure and cardiovascular reflexes, respiration, central chemosensitivity and pain. In the present study, we examined anatomic relationships of the human nucleus paragigantocellularis lateralis using a bidirectional lipophilic fluorescent tracer, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), in nine postmortem human fetal midgestational brainstems. The areas which were labeled by diffusion of DiI from the nucleus paragigantocellularis lateralis included the arcuate nucleus (ARC) of the medulla, caudal raphe (nucleus raphe obscurus and pallidus), hilum and amiculum of the inferior olive, bilateral “reticular formation” (including the nucleus paragigantocellularis lateralis, nucleus gigantocellularis and the intermediate reticular zone (IRZ)), vestibular and cochlear nuclei, cells and fibers at the floor of the fourth ventricle with morphologic features of tanycytes, parabrachial nuclei (PBN), medial lemniscus, lateral lemniscus, inferior cerebellar peduncle and cerebellar white matter, central tegmental tract, and the capsule of the red nucleus. This pattern of DiI labeling bears many similarities with the pattern of connections of the nucleus paragigantocellularis lateralis previously demonstrated by tract-tracing methods in experimental animals, and is consistent with the role of the nucleus paragigantocellularis lateralis in central regulation of homeostatic functions. In contrast to the animal studies, however, we did not demonstrate connections of the nucleus paragigantocellularis lateralis with the nucleus of the tractus solitarius (nTS) (only connections with the rostral subdivision were examined), locus coeruleus, or the periaqueductal gray (PAG) in the human midgestational brainstem. In our previous studies, six medullary areas showed reduced serotonin receptor binding in a subset of victims of sudden infant death syndrome (SIDS). The present study demonstrated DiI labeling in all of these six areas, suggesting that they are interconnected.