New Model of Human Red Nucleus Figure 11. Human parvicellular red nucleus. Photomicrographs showing the distribution of Nissl-stained pNr cells in A(1), B(3), C(4), E(7), and F(10) which correspond to sections 1, 3, 4, 7 and 10 of Fig. 10 and the distribution of myelinated fiber bundles stained by myelin stain in D which corresponds to section Fig. 10B. The number in the left corner of each photomicrograph is the rostrocaudal distance (in micrometers) from the rostral tip of the red nucleus. CTT–central tegmental tract, dmpNr–dorsomedial part of parvicellular red nucleus, EW–Edinger-Westphal nucleus, FR–fasciculus retroflexus, MLF–medial longitudinal fasciculus, MTT–medial tegmental tract, NB–nucleus accessorius medialis of Bechterew, ND– nucleus of Darkschewitsch, Nint–interstitial nucleus of Cajal, vlpNr–ventorlateral part of parvicellular red nucleus. Scale bar = 200 mm in F (also applies to A–E). doi:10.1371/journal.pone.0006623.g011 the same topographical pattern of the projection from the subnuclei of pNr to the dl of PO. However, the possibility that dmpNr and vlpNr project to vl- and dl of PO, respectively still remains. We also showed the point to point projection between the ND and the rostral half of MAO: i.e., in the cat, the medial part of the ND projects to the lateral part of the rostral MAO and the lateral part of the ND to the medial part of the rostral MAO (Onodera and Hicks, 1995 [33]). The present data from the macaque show a new rostro- caudal relationship between the ND and rostral MAO. In macaque, the rostral and caudal part of the ND project to the caudal and rostral part of the rostral MAO, respectively. Therefore the topographical relationship of projections connecting the ND and the rostral MAO is inversely related. Based on these considerations it appears reasonable to propose that the mesodiencephalo-olivary projections of cat and macaque have essentially the same pattern, although there is a difference in the pNr of the cat. Therefore we conclude that fundamentally, quadrupeds have a similar topo- graphical olivary projection from the mesodiencephalic nuclei as we know is the case for the cat (compare Fig. 13A and B). By contrast, the human red nucleus as well as that of the chimpanzee shows other specialized features, i.e., an anatomically isolated ND alongside a well-developed, egg-shaped red nucleus. Comparative neuroanatomical studies of primates have shown that the separation of ND and NB began at the divergence point between ape and monkey [34]. The marmoset and macaque possess a continuous zone consisting of the ND, NB and pNr, similar to the cat. The gibbon represents a transition species with respect to the connection between ND and its prominently well-developed NB. Such a well-developed NB and dmpNr may have been related to the evolutionary development of the frontal cortex containing the FEF, since the NB and its adjacent dmpNr receives a projection from the FEF and its adjacent frontal cortex in macaque [35,36,37,5,38]. As with the human, the chimpanzee exhibits a complete separation between ND and its well-developed red nucleus [34]. Actually the human red nucleus does not present the same appearance as the neural sheet-like appearance of the cat’s and monkeys red nucleus. However the human red nucleus likely has fundamentally the similar topographical relationship as that of the PLoS ONE | www.plosone.org 13 August 2009 | Volume 4 | Issue 8 | e6623