New Model of Human Red Nucleus Figure 6. Distribution of WGA-HRP-labelled cells in mesodiencephalic structures (case 4). Drawings are arranged rostrocaudally; section A is the most rostral. One dot represents one labelled cell. Large dot shows a large labelled cell. dmpNr–dorsomedial part of parvicellular red nucleus, FR–fasciculus retroflexus, mNr–magnocellular red nucleus, NB–nucleus accessorius medialis of Bechterew, ND–nucleus of Darkschewitsch, Nint– interstitial nucleus of Cajal, vlpNr–ventorlateral part of parvicellular red nucleus, III–oculomotor nucleus. doi:10.1371/journal.pone.0006623.g006 the NB, but few were observed in the ND, the Nint, the lateral part of the vlpNr or the mNr (Fig. 9). In the contralateral side a few labeled terminal arborizations were observed only in the NB (Fig. 9E and F). The more caudo-lateral parts of vlpNr were penetrated by larger fiber bundles of the superior cerebellar peduncle, judging from the size of the unlabelled area (compare Fig. 9C and G). This case demonstrates that in the macaque, dmpNr and NB are targeted by the middle premotor and FEF regions, however projection to the ND has yet to be definitively shown. Owing to the unlabeled area, the leg-foot region of the premotor area can be said to project to the lateral part of the vlpNr, and F5 to the NB. Myelo- and Cytoarchitecture of the Human Red Nucleus (Figs. 10,11,12) Using a series of sections prepared with a myelin (Figs. 10 and 11D), and Nissl (Figs. 10, 11 and 12) stain, we observed the mesodiencephalic nuclei consisting of the ND and the red nucleus. Myelin staining of brain sections shows that the fiber bundles of the superior cerebellar peduncle penetrate the center of the red nucleus at an angle from a caudo-medial to rostro-lateral direction and also wrap around the outer surface of the red nucleus like a capsule (Fig. 10). The FR penetrates and contacts the dorsomedial part of the red nucleus (sections 2–4 in Fig. 10). This dorsomedial part of the red nucleus is considered as corresponding to the human NB because this oval area shows microscopical-level features (i.e., more densely packed cells) that correspond more to the periaquaductal gray matter than they do to the reticular formation, similar to what is seen in the feline NB (see also Fig. 11D). Furthermore, fine myelinated fibers vertically rose from the NB and joined the medial part of the CTT (Fig. 11D). We conclude that the FR takes a radically different course with respect to the NB compared to cat and macaque: i.e., in the human the FR passes through the medial side of the NB, whereas in the cat and macaque, the FR passes through the lateral side of the NB and dmpNr. At this level, the ND is separated from the red nucleus by fiber bundles consisting of the superior cerebellar peduncle, CTT, MTT and MLF and is thus isolated in the ventral central gray (Figs. 10B–D, sections 4–8 in Fig. 10). At the level of the oculomotor nucleus, oculomotor nerve fibers run along the surface of the red nucleus whereas caudally the many fiber bundles of the superior cerebellar peduncle penetrate the tail of the red nucleus (Figs. 10E–G, sections 10–14 in Fig. 10). Some rubral neurons remain at the ventrolateral part (Fig. 10G, section 12 in Fig. 10) of the tail of the red nucleus; this corresponds to the caudal part (section N in Fig. 2) of the cat’s vlpNr. Efferent fibers from rubral neurons emerge from the dorsomedial part of the red nucleus, penetrate the cellular layer and its outer capsule of the fiber bundle, and then descend as the CTT to the inferior olive. The medial part PLoS ONE | www.plosone.org 8 August 2009 | Volume 4 | Issue 8 | e6623