Figure 13. Neural sheet model of red nucleus. A. In the cat, the poorly-developed neural sheet curves. B. In the macaque, the moderately developed neural sheet curves. C. In the human, the extremely well-developed neural sheet is completely rolled. The human NB is defined as the dorsomedial part of the red nucleus and it projects to the vl of PO via the medial part of the CTT. A strong stream of these well-developed CTT fibers separates the NB from ND. The gray color indicates a ‘‘still uncertain’’ projection. CTT–central tegmental tract, dmpNr–dorsomedial part of parvicellular red nucleus, lb–lateral bend, MAO–medial accessory olive, MTT–medial tegmental tract, NB–nucleus accessorius medialis of Bechterew, ND–nucleus of Darkschewitsch, PO– principal olive, vl–ventral lamella, vlpNr–ventorlateral part of parvicel- lular red nucleus. doi:10.1371/journal.pone.0006623.g013 Three-Dimensional Model of the Cat’s and Macaque’s Red Nucleus (Fig. 14A and B) Our three-dimensional (3D) models (Fig. 14A and B) of the feline and macaque’s red nucleus were enabled through the use of WGA-HRP-labelled serial sections from the cat (Fig. 2) and the macaque (Figs. 5, 6 and 9). The fundamental structure of the macaque’s 3D model was the same as the cat’s 3D model. The macaque’s vlpNr is well-developed compared with the cat’s vlpNr. Larger fiber bundles of the superior cerebellar peduncle penetrated more caudo-lateral parts of the pNr, while smaller fiber bundles penetrated more rostro-medial parts of the pNr. New Model of Human Red Nucleus Rolled-Sheet Model of the Human Red Nucleus (Fig. 14C) The two models of the human red nucleus based on cytoarchitecture and referred to here have been proposed earlier. The first model was introduced by Grofova´ and Marˇsala (1960) [40] and it represents a polyhedron shape that is covered by several irregular zones that have relatively greater cellular density. In the wide, central area of pNr there are rarely-seen scattered neurons that are separated by strong bundles of myelinated fibers. It is impossible always to identify unambiguously the form and extent of the above-mentioned zones in each case, as the criteria useful for the identification of each cellular zone are imprecise. It is useful to keep uppermost in mind that the human red nucleus is covered by a dense cellular layer. The second model was published by Olszewski and Baxter (1982) [41] and it was described as consisting of three subnuclei: pars oralis, pars dorsomedialis and pars caudalis. The pars oralis is the oral pole of the red nucleus. The pars dorsomedialis is separated from oralis by a lamella of myelinated fibers and the cell density of these two parts is higher than in pars caudalis. The pars caudalis is traversed by many fiber bundles within which its constituent cells are loosely and irregularly arranged. We would like to propose a third model we name as ‘‘rolled sheet’’. This is based in part on a combined myelo- and cytoarchitectonic analysis, considered together with the above two preceding models, plus a consideration of the common topographical olivary projection (see Fig. 13). A dense cellular layer of the pNr envelops huge myelinated fiber bundles of the superior cerebellar peduncle. These fiber bundles branch off collateral terminals to the pNr neurons and pass through the center of the red nucleus in a dorsolateral direction. These passing fibers ascend through the dorsolateral opening to the thalamus and descend from the cortex. The caudomedial end of the red nucleus forms a ring-like structure allowing for the entrance of the cerebellar peduncle and the elongated bulge of the ventolateral wall (i.e., caudal end of vlpNr). The dorsomedial part of the rostral red nucleus is a densely packed cell mass that is divided by a lamella of myelinated fibers (see Fig. 11D). We defined this dorsomedial region and its caudal continuation as the NB. The rostral pole of the red nucleus forms a cell mass appearing like a set of lips (see Fig. 11A); dense cellular layers contact each other to look like closed lips and these possess a few penetrating myelinated fiber bundles. The outer surface of the red nucleus is formed by densely packed cells and furthermore is covered by a dense, myelinated fiber capsule; the inner surface of the rolled sheet is formed by loosely and irregularly arranged cells and is penetrated by large collateral fiber bundles of the superior cerebellar peduncle. Therefore the human red nucleus may be considered to be classified as a typical ‘‘closed nucleus’’ just as the cat’s red nucleus is (Mannen, 1988 [2]), although there are other differences between the parvicellular red nucleus for the human and the magnocellular red nucleus for the cat. Both giant and large mNr neurons are located in dorsal and ventral groups caudal to the vlpNr (see Figs. 10 and 12E, F and G). Some large, medium and small mNr neurons also are scattered outside the outer capsule of the red nucleus (Fig. 12A, B and E). These mNr neurons form a semi-lunar shell at the caudal end of vlpNr, and are considered a homologue of the cat’s and macaque’s mNr, judging from their positions (compare Fig. 14A, B and C). In the monkey, neurons with a coarse Nissl pattern (i.e., mNr neurons) extend for a short distance along the lateral side of fine neurons (i.e., pNr neurons) in the rostral part of the red nucleus [42]. This short dorsolateral extension of the monkey’s mNr corresponds to the semilunar shell. The gibbon mNr is laminated and rotated about its major axis [43]. This feature seems equivalent to the semilunar PLoS ONE | www.plosone.org 15 August 2009 | Volume 4 | Issue 8 | e6623