Observations on the secondary vestibulocerebellar projections in the macaque monkey.

The distribution of retrogradely labeled cells in the nuclei of the vestibular nuclear complex following injections of horseradish peroxidase in various parts of the cerebellar cortex (except the nodulus and paraflocculus) has been mapped in the macacus rhesus monkey. In the main the findings correspond to those made in other mammalian species (cf. Table 1). The flocculus receives afferents bilaterally from the superior, medial and descending vestibular nucleus, group y, the interstitial nucleus of the vestibular nerve and also from the abducent nucleus. The projection to the posterior vermis (lobules VIII and IX), especially to lobule IX, is more abundant than that to lobules VI-VII. The projection to the anterior lobe vermis appears to be modest. Evidence for projections to the cerebellar hemispheres was not obtained. Whether the lateral vestibular nucleus projects to the cerebellum in the macaque is uncertain. The regular occurrence of weakly labeled cells among heavily labeled ones suggests that many of the cerebellar projecting cells may have axonal branches passing to other destinations. The findings lend support to the notion that there are precise topical relations within the entire secondary vestibulocerebellar projection. For example, in the medial nucleus the sites of origin of fibers to the flocculus and uvula are different. Surprisingly, many cells in group z were found to project to the uvula and - to a lesser extent - to lobule VIII. The group z may, therefore, not be a pure relay nucleus in a spinothalamic pathway, as generally assumed. The rather marked cerebellar projection of the abducent nucleus, especially to the flocculus, is of interest for the analysis of cerebellar control of eye movements in the macaque.

The vestibular nuclei in the macaque monkey.

The topography and the main features of the cytoarchitecture of the vestibular nuclear complex in the macaque monkey have been studied in serially cut, Nissl-stained, transverse, parasagittal and horizontal sections. In addition to the four main vestibular nuclei, the topographically closely related small cell groups (f, l, x, y, and z), distinguished by Brodal and Pompeiano ('57) in the cat, have been considered and illustrated. The vestibular nuclear complex in the macaque in general corresponds in topography and architecture to the situation described in some other mammals on which information is available, such as opossum, rabbit, cat, Galago, and man. Some dissimilarities in detail are found. For example, in man the lateral vestibular nucleus differs somewhat from the general pattern, especially in its position, and the small group f, fusing with the descending nucleus, appears to be indistinct; likewise the group y. The latter and the group z appear to be particularly well developed and easily distinguished in the macaque. The question of whether cytoarchitectonic areal differences within the vestibular nuclear complex can be correlated with differences in connections is discussed. Also in this respect there appears to be a general similarity between observations in the macaque and in other mammals. A correlation is most evident in the superior vestibular nucleus, and is rather clear in the medial and lateral vestibular nuclei and for the groups f,x,y, and z, whereas no such correlation can be found in the descending (inferior) nucleus. For several reasons it is difficult to draw reliable conclusions about comparative anatomical trends in the phylogenesis of the vestibular nuclear complex.

Observations on the projection from the perihypoglossal nuclei onto the cerebellum in the macaque monkey.

The occurrence and distribution of retrogradely labeled cells in the perihypoglossal nuclei of the monkey were mapped after injections of horseradish peroxidase in various cerebellar cortical regions. In general the findings are in accord with those made in the cat. The flocculus receives a heavy bilateral projection from the nucleus prepositus, particularly from its caudoventral part, and from the nucleus of Roller. There is an apparently scanty projection from the nucleus intercalatus. The uvula receives a rather similar projection, but in the prepositus the cells projecting to the uvula are on the whole situated more dorsally and rostrally than those supplying the flocculus. The projection to lobules VII-VIII is distinct. More scanty projections have been found to the paramedian lobule and the anterior lobe. The different but partially overlapping sites of origin in the prepositus of fibers to the flocculus and uvula indicate the presence of a topical pattern within the perihypoglosso-cerebellar projection, as in the cat (34). In the monkey the two regions of origin appear to coincide with two particular cell collections in the prepositus (12). Both small and middle sized cells project to the cerebellum, as they do in the cat (9, 48). The nucleus supragenualis nervi facialis in the macaque is morphologically different from the corresponding nucleus in most other mammalian species (12), but it contains labeled cells after injections in the flocculus, uvula and other cerebellar regions. A considerable number of cells in the abducent nucleus are labeled after injections in the flocculus and the posterior vermis.

The perihypoglossal nuclei in the macaque monkey and the chimpanzee.

The topography of the perihypoglossal nuclei (nucleus intercalatus, nucleus prepositus, and nucleus of Roller) of the macaque and the chimpanzee was studied in serial Nissl-stained sections through the brainstem. Maps of the nuclei in the two species are presented. Although in both species the perihypoglossal nuclei are organized according to the general mammalian pattern, they show some particular features, reflecting in part, an increasing phylogenetic differentiation. In the chimpanzee the nucleus prepositus is relatively larger, the nucleus of Roller is more of a separate unit, and its cellular composition is more uniform than is the case in the macaque. A cellular connection between the two nuclei is present in the macaque (even more conspicuous in the cat, apparently absent in man), but is barely discernible in the chimpanzee. A conspicuous difference between the chimpanzee and the macaque concerns the nucleus supragenualis nervi facialis, forming a rostral continuation of the prepositus. In the chimpanzee it is a loosely structured region of small cells (as in the cat and in man). In the macaque, however, it appears as a rather well-delimited column of chiefly medium-sized cells. Some comparative anatomical and functional aspects are discussed. Many contingents of afferents to--and efferents from--the nucleus prepositus have their preferential sites of termination or origin in the nucleus, although with considerable overlapping. This indicates the presence of topical patterns in the prepositus. In general the caudal parts appear to be more related to the cooperation with the cerebellum than the rostral part, whereas the latter appears to be more particularly linked with the oculomotor apparatus.

A re-evaluation of the question of ascending fibers in the pyramidal tract.

In 1952 we published a study in the cat with the Glees method, demonstrating the occurrence of degenerating fibers in the pyramidal tract rostral to transections of the tract in the spinal cord. These fibers were interpreted as spinocortical fibers, which have also been described in man. However, other authors have disputed the existence of such fibers. In an attempt to provide more information about this subject, multiple injections of horseradish peroxidase (free and lectin-labeled) were made in the sensorimotor cortex of 4 cats. No retrogradely labeled cells were found in the spinal cord in these cases. Our present and previously reported findings are discussed in the light of other studies of pathological changes in fiber tracts within the central nervous system. Although the present experiments were negative, the degenerating axons previously observed by us in silver sections from the pyramid, pons and internal capsule after lesions of the pyramidal tract in the spinal cord, can not be satisfactorily explained as evidence of retrograde, indirect Wallerian, degeneration of corticospinal fibers.

Further observations on the olivocerebellar projection in the monkey.

The distribution of retrogradely labeled cells in the inferior olive was studied following cerebellar injections of horseradish peroxidase in four experiments in macaque monkeys. The flocculus was found to receive its main projection from the dorsal cap and a minor projection from the medial accessory olive. The uvula receives fibers from the nucleus beta, the dorsomedial cell column and from an area of the medial accessory olive. The paramedian lobule is supplied from the dorsal and ventral lamella of the principal olive and from an area in each of the accessory olives. The findings are considered in the light of our more extensive information of the olivocerebellar projection in the cat and with reference to present knowledge of the longitudinal subdivision of the cerebellum in the cat. In general the principal organization appear to be the same in the cat and the monkey, in spite of some species differences. Thus the olivary area projecting to zone C2 (rostral part of the medial accessory olive) appears to be relatively larger in the monkey than in the cat. The same appears to be the case for the dorsal lamella of the principal olive and its cerebellar projecting zone D (probably zone D1).

The olivocerebellar projection in the monkey. Experimental studies with the method of retrograde tracing of horseradish peroxidase.

Following injections of horseradish peroxidase (HRP) in various lobes and lobules of the macaque cerebellum the occurrence of retrogradely labeled cells in the inferior olive was mapped. Only cortical areas showing staining of the molecular layer were considered as sites of uptake of HRP. To facilitate comparisons between cases and presentation of findings, a diagram of the macaque inferior olive as imagined unfolded was constructed (Fig. 1). Attempts were made to compare the findings made with data on the olivocerebellar projection in the cat and the pattern of a longitudinal zonal subdivision of the cerebellum. In general there appears to be a remarkably close correspondence between the organization of the olivocerebellar projection in the monkey and the cat. The projection is precisely organized and appears to be purely crossed. Within the projections to some of the cerebellar cortical zones a topical pattern can be demonstrated. Olivary afferents to vermal lobules V, VII, and VIII are derived from the caudal half of the medial accessory olive, projecting to Voogd's zone A. The topical pattern resembles that in the cat (Fig. 8). after injections covering the lateral zone of the anterior lobe vermis (zone B), labeled cells are seen in the caudal part of the dorsal accessory olive. In some cases staining of the intermediate part of the anterior lobe and of the paramedian lobule is followed by labeling of cells in the rostral part of the dorsal accessory olive (zones C1 and C3) or in the rostral half of the medial accessory (zone C2). When the injected area covers lateral parts of the cerebellum, there is labeling in the principal olive (projecting to zones D1 and D2). Although not entirely decisive, the findings lend support to the view that the ventral lamella of the principal olive supplies zone D2, whereas the dorsal lamella supplies zone D1. The relatively sparse data in the literature on the afferents to the monkey olive are briefly considered. On may points the projections appear to be as in the cat. However, there is possibly a species difference between cat and monkey as concerns their receipt of afferents from the red nucleus.

The longitudinal zonal pattern in the paramedian lobule of the cat's cerebellum: an analysis based on a correlation of recent HRP data with results of studies with other methods.

In a preceding study of the distribution of retrogradely labeled cells in the inferior olive of the cat after microinjections of horseradish peroxidase (HRP) in the contralateral paramedian lobule (Brodal and Walberg, '77b), three longitudinal zones were distinguished. The zones were assumed to correspond to Voogd's zones C1, C2 and D, receiving their afferents from parts of the dorsal accessory olive, of the medial accessory olive and of the dorsal lamella of the principal olive, respectively. Labeled cells were not found in the ventral lamella of the principal olive, however, although there is no doubt that also this projects to the paramedian lobule. In the present study, iontophoretic ejections, covering the extreme lateral part of the paramedian lobule, gave rise to labeling of cells in the ventral lamella. It is concluded that the zone D in the paramedian lobule can be subdivided into two, a lateral, D2, and a medial, D1, receiving fibers from the ventral and dorsal lamella, respectively. Neither zone extends throughout the entire length of the paramedian lobule. Both are lacking most rostrally and most caudally. This and other findings prompted a renewed analysis of the entire pattern of zonal representation in the paramedian lobule, based on correlations of our observations with the HRP method with data obtained with other methods. The results of this analysis are briefly described and summarized in a diagram (fig. 3B). It is particularly remarkable that zone B is present in some folia medially. A somatotopical arrangement appears to be present within all zones. A full account and documentation will be presented separately (Brodal and Kawamura, '80).

The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase. VII. The projection to lobulus simplex, crus I and II.

The olivocerebellar projection to lobulus simplex, crus I and II in the cat was investigated by means of retrograde axonal transport of horseradish peroxidase (HRP). The distribution of labeled cells in the inferior olive following HRP injections in lobulus simplex, crus I and II confirmed the findings by Brodal ('40b) that the rostral half of the principal olive projects to these areas of the cerebellar hemisphere. However, concerning details there are some differences in so far as the heaviest contribution to crus I comes from the medial parts of the ventral and dorsal lamella, that to crus II from its lateral part, especially the ventral bend. The present findings show that in addition the rostral part of the medial and the rostromedial part of the dorsal accessory olive project to these areas of the cerebellar cortex. Further details in the projection are shown in figure 8B. The findings agree fairly well with the electrophysiological results of Armstrong et al. ('74) and the experimental anatomical data of Groenewegen and Voogd ('77a,b). An attempt is made to correlate the findings with the pattern of longitudinal zonal subdivision of the cerebellum. There is evidence for a topical organization within the projection to crus I and II and parts of their projection areas in the principal olive. The distribution of the labeled cells which project to lobulus simplex, crus I and II is discussed in relation to afferent pathways to the inferior olive.

The pontocerebellar projection of the uvula in the cat.

The occurrence of retrogradely labeled cells in the pontine nuclei was mapped following injections of 0.3-0.4 microliter of a horseradish peroxidase suspension (50% weight/volume) into the uvula (lob. IX of Larsell) in the cat. The uvula was found to receive afferents from three pontine cell collections. One of these is situated in the paramedian pontine nucleus close to the midline. It forms a fairly distinctly outlined longitudinal column of cells and is present at all levels of the pons except most rostrally and caudally. Another group, in the dorsolateral and lateral pontine nuclei, extends as a somewhat shorter cell column in the longitudinal direction. The third region consists of cells within the rostral part of the peduncular nucleus in its dorsomedial region. The pontine projection to the uvula is bilateral, with some preponderance of crossed connections. The projection to the uvula is organized according to the pattern determined previously for pontine projections to other parts of the cerebellum. A single lobule or part of its receives afferents from more than one cell group in the pons. The projecting cells are most often arranged in longitudinal columns. Correlations with data on the termination of afferents to the pons permit some conclusions regarding the sources of information reaching the uvula via the pons. Main sources seem to be the superior and inferior colliculi, the intracerebellar nuclei and the sensorimotor cortices.

The olivocerebellar projection studied with the method of retrograde axonal transport of horseradish peroxidase. V. The projections to the flocculonodular lobe and the paraflocculus in the rabbit.

HRP was injected in the flocculonodular lobe and the paraflocculus in the rabbit to determine the areas of the inferior olive which project onto these cerebellar regions. Following injections in the flocculus labeled cells occurred in the dorsal cap and the rostralmost tip of the medial accessory olive. Following injections in the nodulus labeled cells were likewise found in the dorsal cap, but in addition in the rostralmost part of the dorsomedial cell column and the adjoining part of the medial accessory olive. Injections in the dorsal paraflocculus gave rise to labeling in the rostrolateral part of the medial accessory olive, while injections in the ventral paraflocculus resulted in labeling in the principal olive, mainly in the lateral part of the ventral lamella. Injections in the lateral third of the dentate nucleus gave rise to labeling mainly in the dorsal lamella of the principal olive. The results are discussed with reference to those obtained by previous authors. There are both similarities and discrepancies. It appears from what is known of afferents from areas mediating visual impulses to the inferior olive that the olivary areas projecting onto the flocculonodular lobe, and possibly the dorsal paraflocculus, may mediate visual impulses to these lobules.