Projections of the cerebellar and dorsal column nuclei upon the inferior olive in the rhesus monkey: an autoradiographic study.

Projections from the cerebellar and dorsal column nuclei to the inferior olive of the rhesus monkey were traced with anterograde autoradiographic methods. The cerebellar nuclei give rise to a massive projection which reaches the contralateral inferior olivary complex by way of the descending limb of the superior cerebellar peduncle. Dentato-olivary fibers project exclusively upon the principal olivary nucleus (PO) and observe a strict topography. The dorsal, lateral, and ventral dentate project respectively to the dorsal, lateral, and ventral lamellae of the PO. Within the lamellae, the dentato-olivary fibers are related point for point in the medio-lateral axis. By contrast, the rostro-caudal topography is reversed so that the rostral pole of the dentate projects to the caudal PO and the caudal dentate to the rostral PO. These connections are predominantly crossed but a small ipsilateral component recrosses the midline at the olivary commissure and mirrors the topography on the opposite side. The anterior interpositus projects only to the medial half of the DAO and the posterior interpositus projects only to the rostral two thirds of the MAO. The ipsilateral component is minor in comparison with the contralateral projection, but appears to be more substantial than the ipsilateral projection to the PO arising from the dentate nucleus. The fastigial nucleus does not project upon the olivary complex. The dorsal column nuclei project topographically upon the contralateral accessory nuclei with the gracile nucleus sending fibers primarily to the lateral half of the DAO and the cuneate nucleus projecting to rostral cell groups of the MAO. The present results when compared with other olivary connections described by previous studies in a variety of species suggest that regions of the MAO and DAO receiving sensory information from the periphery may lie outside the influence of cerebellar feedback loops.     

An autoradiographic study of the rubroolivary tract in the rhesus monkey.

Autoradiographic tracing methods were employed to study the course and distribution of the rubroolivary tract following unilateral injections of tritiated leucine into the rostral red nucleus of seven rhesus monkeys. A topographic organization of projections to the ipsilateral principal nucleus of the inferior olivary complex was demonstrated. Lateral and medial portions of the rostral red nucleus projected to medial parts of the dorsal and ventral laminae of the principal inferior olive respectively; neurons in intermediate lateralities emitted fibers which terminated in lateral parts of the principal olive. Injections involving the oral end of the rostral red nucleus elicited label overlying the medial accessory olive in addition to the principal nucleus. Projections to the medial accessory olive may have arisen from the rostral end of the red nucleus and/or the immediately adjacent tegmentum. There were no projections to the dorsal accessory olive. Fibers of rubral origin also were distributed ipsilaterally to several reticular nuclei including the pedunculopontine, pontis oralis, caudalis, and gigantocellularis.     

Cerebello-olivary projections in the rat: an autoradiographic study

The cerebello-olivary projection was studied in the albino rat using conventional autoradiographic techniques. The results indicated that the cerebello-olivary projection in the rat is topographically organized in a pattern similar to other mammalian species. The anterior interpositus projects to the dorsal accessory olive, the posterior interpositus to the medial accessory olive, and the dentate to both lamellae of the principal nucleus. A point of controversy may arise, however, when one considers the fastigio-olivary projection.     

GABAergic neurons in the mammalian inferior olive and ventral medulla detected by glutamate decarboxylase immunocytochemistry.

Neurons containing glutamic acid decarboxylase (GAD) (presumed GABAergic neurons) were mapped by immunocytochemistry in the ventral medulla of rat, rabbit, cat, rhesus monkey, and human, with emphasis on the inferior olive. In all species, three categories of GABAergic neurons were identified: periolivary neurons in the gray matter and the white matter surrounding the inferior olive, internuclear neurons located in the white matter between the subnuclei of the inferior olive, and intranuclear neurons located within the olivary gray matter. The intranuclear GABAergic neurons of the inferior olive had a characteristic morphology which differed from non-GABAergic olivary neurons; they were usually smaller, and, wherever their processes were stained, they had radiating, sparsely branching dendrites. They were also usually distinguished from the other GABAergic neurons by their smaller size. The intraolivary GABAergic neurons constituted only a minor proportion of the total olivary neuronal population, but they were concentrated in regions of the olive that varied by species. In the rat, they were situated in the rostral tip of the medial accessory olive and in the caudal subdivision of the dorsal accessory olive, while in the rabbit, they were located in the caudal two-thirds of the medial accessory olive, in the dorsal cap, and in the ventral lateral outgrowth. Such neurons were extremely rare in the cat; only a few were found in the rostral parts of the principal olive, the medial accessory olive, and the dorsal accessory olive. In the rhesus monkey, the principal olive and the lateral region of the rostral medial accessory olive contained most of the intranuclear GABAergic neurons, but some were also present in the dorsal accessory olive. In the human, such neurons occurred in the principal olive, the dorsal accessory olive and the rostral medial accessory olive, but as in the rhesus monkey, most were observed in the principal olive.     

Cerebellothalamic projections in the rat: An autoradiographic and degeneration study

The purpose of this study was to determine the topographical organization of cerebellothalamic projections in the rat. Following stereotaxic injections of ³H-leucine or electrolytic lesions in the cerebellar nuclei, efferent fibers were observed to emerge from the cerebellum through two discrete routes. Fibers from the fastigial nucleus decussated within the cerebellum, formed the crossed ascending limb of the uncinate fasciculus, ascended in the dorsal part of the midbrain tegmentum, and entered the thalamus. Cerebellothalamic fibers from the interpositus and dentate nuclei coursed in the ipsilateral brachium conjuctivum, decussated in the caudal midbrain, and ascended to the thalamus via the crossed ascending limb of the brachium conjunctivum. Cerebellar terminations were observed in the intralaminar, lateral, and ventral tier thalamic nuclei as well as in the medial dorsal nucleus. Projections to the intralaminar nuclei were more pronounced from the dentate and posterior interpositus than from the anterior interpositus and fastigial nuclei. The lateral thalamic nuclei received a projection from the dentate and posterior interpositus nuclei while the fastigial nucleus projected to the medial dorsal nucleus. Within the rostral ventral tier nuclei fastigiothalamic terminations were localized in the medial parts of the ventral medial and ventral lateral nuclei, whereas dentatothalamic projections were concentrated in the lateral parts of the ventral medial nucleus and the medial half of the ventral lateral nucleus. Terminations from the posterior interpositus nucleus were observed ventrally and laterally within the caudal two-thirds of the ventral medial nucleus and throughout the ventral lateral nucleus, where they were densest in the lateral part of its lateral wing and within the central part of its cap. The anterior interpositus nucleus also projected to the central and lateral parts of the ventral lateral nucleus, but these terminations were considerably less dense than those from the posterior interpositus. A few fibers from the interpositus nuclei terminated in the medial part of the rostral pole of the ventral posterior nucleus. A prominent recrossing of cerebellothalamic fibers from the fastigial, posterior interpositus, and dentate nuclei occurred through the central medial nucleus of the internal medullary lamina. These terminated within the ipsilateral ventral lateral and intralaminar nuclei. These results show that each of the cerebellar nuclei project to the thalamus and that their terminations are topographically organized in the rostral ventral tier nuclei. The clustering of autoradiographic silver grains or terminal degeneration observed in the thalamic nuclei suggests a medial-to-lateral organization of this cerebellothalamic system.     

Olivocerebellar projections to paramedian lobule in tree shrew (Tupaia glis): a horseradish peroxidase study

Horseradish peroxidase (HRP) was used as a retrograde tracer to identify the distribution pattern of labeled cells in the inferior olivary nucleus (IO) of Tupaia. Crystallized HRP was implanted into dorsal (DPML) and ventral (VPML) divisions of the paramedian lobule (PML) and, following appropriate survival times, the tissues were processed using diaminobenzidine and tetramethylbenzidine as chromogens. Subsequent to implants into lateral DPML and VPML, HRP-labeling is seen in rostral subgroup a of the medial accessory olive (MAO) and in the medial part of the dorsal accessory olive (DAOm) and ventral lamellae of the principal olive (VLPO) close to their rostral poles. The lateral bend and adjacent dorsal lamella of the principal olive and rostral subgroup c of MAO also contain HRP-reactive somata following lateral DPML implants. Subsequent to implants in central DPML, labeling is seen in rostral DAOm and subgroup a of MAO. Central VPML implants result in additional clusters of labeled cells in VLPO, the lateral bend of the principal olive (PO), and subgroup c of MAO. Following implants of HRP into medial PML reactive somata are found in dorsomedial VLPO and DLPO, and clusters of labeled cells are present in caudal subgroup a of MAO and DAOm. In contrast to implants in central and lateral PML, rostral DAOm and PO are devoid of reactive neurons. These results show that olivocerebellar projections to PML of Tupaia are exclusively contralateral and topographically organized. Collectively these olivocerebellar data corroborate the existence of zones C1, C2, C3 and D in PML of Tupaia and show that their patterns are similar, in their essential features, to those seen in the corticonuclear pathway in this species.     

The trigemino-olivary projection in the cat: contributions of individual subnuclei

Anterograde autoradiographic methods were used to determine the projection of the principal sensory trigeminal nucleus and of each of the three spinal trigeminal subnuclei to the inferior olivary complex in the cat. Our data reveal that the principal sensory trigeminal nucleus does not contribute to the trigemino-olivary pathway. Each spinal trigeminal subnucleus has a unique contribution to this pathway: pars oralis projects sparsely to the border between the dorsal accessory and principal olives (DAO-PO), pars interpolaris projects mostly to the rostral medial DAO, and pars caudalis projects mostly to the rostral medial part of the ventral leaf of PO and slightly to the caudal medial accessory olive. In the light of recent physiological and anatomical findings, our data indicate that information from each spinal trigeminal subnucleus reaches a different segment of the contralateral inferior olivary complex, which in turn distributes differentially to the cerebellar cortex.     

Projections from the inferior olive to the cerebellar nuclei in the cat demonstrated by retrograde transport of horseradish peroxidase

The method of intracerebral injections of horseradish peroxidase has been applied to demonstrate a projection from the inferior olivary nucleus to the intracerebellar nuclei in the cat. Cells labeled by the transported enzyme can be observed in different regions of the olive according to the localization of the injection. The caudal half of the medial and dorsal accessory subdivisions, the dorsal cap and nucleus β project to the fastigial nucleus. In the rostral half of the olive, the accessory subdivisions of that nucleus and the dorsomedial cell column send fibers to the interposed nuclei while the principal olive and the ventrolateral outgrowth are connected with the dentate nucleus. It is likely that these fibers are collaterals of the climbing fibers.     

The organization of cerebellar afferent projections to the paramedian lobule in neonatal cats

This study sought to determine whether cerebellar afferent pathways, that are topographically organized in adult cats, are similarly ordered during the postnatal development and maturation of the cortex, or whether the projections are first distributed randomly in the cortex before becoming organized. Injections of wheat germ agglutinin-horseradish peroxidase were made into dorsal (dPML) or ventral (vPML) divisions of the paramedian lobule (PML) in neonatal (0- to 21-days-old) and adult cats and the ensuing distributions of retrogradely labeled neurons in the lateral reticular nuclei, the inferior olive and the pontine nuclei were compared. Magnocellular and parvicellular neurons in the dorsomedial and dorsolateral parts of the ipsilateral lateral reticular nuclei project respectively to dPML and vPML in all neonatal and adult cats. Olivocerebellar projections were entirely crossed, in most cases, with neurons projecting to the dPML more rostral and medial in the dorsal and medial accessory nuclei and in the principal olive than neurons which project to the vPML. A parasagittal zonal organization of olivocerebellar projections was present in newborn cats. Neurons were labeled in the ipsilateral inferior olive following dPML injections in 1- to 4-day-old kittens, but not in older kittens or in adult cats. Pontocerebellar projections were bilateral with a contralateral predominance. In adult and neonatal cats, labeled neurons were clustered together and formed rostral-caudal oriented columns dorsomedial and ventromedial to the pyramidal tract after injections in the contralateral dPML and vPML and bilaterally in the dorsolateral pons after dPML injections. These results show that lateral reticulo-, olivo- and pontocerebellar projections to the PML which are topographically organized in adult cats are organized similarly in newborn cats. Studies in prenatal cats are required in order to determine whether these cerebellar afferents are ever randomly distributed in the cerebellar anlage or whether these projections are ordered as they grow into the cerebellum.     

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.     

The inferior olive of Saimiri sciureus: Olivocerebellar projections to the anterior lobe

Olivocerebellar projections to lobules IV and V of the anterior lobe of the squirrel monkey (Saimiri sciureus) cerebellum were studied using a wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP). Placements of WGA-HRP in the cerebellar cortex, labeled neurons in different subgroups of the contralateral inferior olive depending on the position of the injection site. Injections in medial aspects of lobules IV and V labeled cells in subgroups a and b of the caudal medial accessory olive (MAO) and in the lateral dorsal accessory olive. Rostral parts of subgroup a of MAO and medial dorsal accessory olive contained labeled neurons when injections were made in intermediate areas of the cerebellar cortex. Subsequent to involvement of more lateral parts of lobules IV and V, labeled cells were found in the dorsal lamella and lateral bend of the principal olive. When the position and size of injection sites were compared to distribution of retrogradely labeled olivary somata, it was clear that zones A, B, C1, C2, C3 and D were present in lobules IV and V of squirrel monkey. The general pattern of olivary labeling in this study is similar to that reported for other species.     

Olivary projections from the mesodiencephalic structures in the cat studied by means of axonal transport of horseradish peroxidase and tritiated amino acids

By means of horseradish peroxidase (HRP) and autoradiographic methods, olivary projections from mesodiencephalic structures were studied in the cat. Following HRP injections in various parts of the inferior olive, many cells were labeled ipsilaterally in the nucleus of Darkschewitsch, the nucleus accessorius medialis of Bechterew, the nucleus of the fields of Forel, and the subnucleus dorsomedialis and ventrolateralis of the parvocellular red nucleus. Some labeled cells also occurred ipsilaterally in the suprarubral reticular formation and a few labeled cells in the interstitial nucleus of Cajal. After injection of tritiated amino acids in different parts of the mesodiencephalic region mentioned above, labeled fibers were found in different parts of the inferior olive, presenting a high degree of the topographic correlation within the mesodiencephalo-olivary projection, which was exclusively ipsilateral. That is, the nucleus of Darkschewitsch was found to project to the rostral half of the medial accessory olive and the dorsomedial cell column. There was mediolateral topographic relation in this projection. The nucleus accessorius medialis of Bechterew was found to project to the ventral lamella and the lateral part of the dorsal lamella as well as to a small rostromedial part of the caudal half of the medial accessory olive. The subnucleus dorsomedialis and ventrolateralis of the parvocellular red nucleus projected to the rostral and caudal halves, respectively, of the medial part of the dorsal lamella. The subnucleus ventrolateralis of the parvocellular red nucleus also sent fibers to the lateral part of the ventrolateral outgrowth. The nucleus of the fields of Forel, suprarubral reticular formation, and interstitial nucleus of Cajal appeared to project to the caudal half of the medial accessory olive, the medial part of the ventrolateral outgrowth, the rostral part of the dorsal cap, and the caudal part of the dorsal accessory olive.     

The cerebellar nucleo-olivary and olivocerebellar nuclear projections in the cat as studied with anterograde and retrograde transport in the same animal after implantation of crystalline WGA-HRP. III. The interposed nuclei

The bidirectional connections between the inferior olive and the cerebellar nuclei were investigated by means of anterograde and retrograde transport after implantation of crystalline wheat germ agglutinin-horseradish peroxidase complex in the interposed nuclei. The projections from the interposed nuclei to the inferior olive show a detailed topical arrangement. The main projection from the anterior interposed nucleus reaches the rostral two thirds of the dorsal accessory olive, while the main projection from the posterior interposed nucleus reaches the rostral half of the medial accessory olive. The projections from the inferior olive to the interposed nuclei show a more widespread distribution and appear to be less precisely organized. Both interposed nuclei receive afferents from the medial and dorsal accessory olives, the dorsomedial cell column, nucleus beta and the dorsal cap. Our findings give evidence that the olivo-interposed and interposito-olivary projections are in part reciprocally organized. Our observations are discussed and related to previous investigations on the cerebello-olivary and olivocerebellar pathways. Some methodological comments are made. It appears from our results that anterograde transport in some of our cases has occurred only from a restricted part of the stained area at the implantation site.     

Neurotransmitter-specific uptake and retrograde transport of [3H]glycine from the inferior colliculus by ipsilateral projections of the superior olivary complex and nuclei of the lateral lemniscus.

Neurotransmitter-specific uptake and retrograde axonal transport of [3H]glycine were used to identify glycinergic projections to the inferior colliculus in chinchillas and guinea pigs. Six h after injection of [3H]glycine in the inferior colliculus, autoradiographically labeled cells were found ipsilaterally in the ventral nucleus of the lateral lemniscus, the lateral superior olive and the dorsomedial periolivary nucleus. These 3 regions accounted for 95% of the labeled projection neurons, with the remainder scattered elsewhere in the ipsilateral superior olivary complex. No labeled cells were found contralaterally even after survival times as long as 24 h. Retrograde transport of HRP from the inferior colliculus in these same cases confirmed the presence of additional projections that did not accumulate [3H]glycine. These included ipsilateral projections from the medial superior olive and cochlear nucleus and contralateral projections from the inferior colliculus, dorsal nucleus of the lateral lemniscus, lateral superior olive, periolivary nuclei and cochlear nucleus. The results implicate uncrossed projections from the ventral nucleus of the lateral lemniscus, lateral superior olive, and dorsomedial periolivary nucleus as the principal sources of inhibitory glycinergic inputs to the inferior colliculus.     

Physiopathology of the cerebellum in the monkey. I. Origin of cerebellar afferent nervous fibers from the spinal cord and brain stem

Complete cerebellectomy is associated with almost total cell loss in the reticulotegmental, lateral reticular and pontine nuclei and in the principal and accessory olivary nuclei but not in the perihypoglossal and reticular paramedian nuclei in the monkey. The latter structure which is a prominent structure in the cat is underdeveloped or absent in this species. It also results in important retrograde degenerating changes of the neurons of the lateral cuneate nucleus, the dorsal nucleus of Clarke and the border cells of Cooper and Sherrington as disclosed in 1 monkey with a short-term cerebellectomy. A few neurons of the principal cuneate nucleus also undergo retrograde degeneration in the immediate postoperative period. The present findings suggest that the caudal part of the medial accessory olive and its “dorsal cap” are anatomically related to the contralateral nodulus and flocculus, respectively, whereas the rostral part of the medial accessory olive is more directly related to the neovermis. The dorsal accessory olive appears to be related to the contralateral cerebellar nuclei and more specifically, the fastigial nucleus. These results also favour the existence of cerebellopetal fibers from the principal cuneate nucleus and of a few non-cerebellopetal fibers from the lateral cuneate nucleus. The present findings support the suggestion of Cooper and Sherrington pointing to the existence of spinocerebellar fibers originating in the border cells of the ventral horn at the level of the low thoracic and lumbar segments of the cord. However the possibility that such “spinocerebellar” fibers may distribute collateral endings to the dorsolateral area of the medulla or even terminate in this area cannot be entirely ruled out on the basis of the present material. A similar feature possibly explains the fact that most (if not all) cells of the dorsal nucleus of Clarke resist the interruption of their axons at cerebellar level as suggested by the findings in monkeys with long standing lesions.     

Organization of projections from the inferior olive to the cerebellar nuclei in the rat

The detailed organization of projections from the inferior olive to the cerebellar nuclei of the rat was studied by using anterograde tracing. The presence of a collateral projection to the cerebellar nuclei could be confirmed, and a detailed organization was recognized at the nuclear and subnuclear level. Olivary projections to the different parts of the medial cerebellar nucleus arise from various parts of the caudal half of the medial accessory olivary nucleus. The interstitial cell groups receive olivary afferents from the intermediate part of the medial accessory olive and from the dorsomedial cell column. A mediolateral topography was noted in the projections from the rostral half of the medial accessory olive to the posterior interposed nucleus. Olivary projections to the lateral cerebellar nucleus are derived from the principal olive according to basically inversed rostrocaudal topography. Projections from the dorsomedial group of the principal olive to the dorsolateral hump were found to follow a basically rostrocaudal topography. The anterior interposed nucleus receives olivary afferents from the dorsal accessory olive. Its rostromedial parts are directed to the lateral part of the anterior interposed nucleus and its caudolateral part reach the medial anterior interposed nucleus. No terminal arborizations in the cerebellar nuclei were found to originate from (1) the dorsal fold of the dorsal accessory olive, which resulted in projections to the lateral vestibular nucleus and (2) the dorsal cap of Kooy. It was noted that the olivary projection to the cerebellar nuclei is strictly reciprocal to the nucleo-olivary projection as described by Ruigrok and Voogd (1990). Moreover, it is suggested that the olivonuclear projection adheres to the organization of the climbing fiber projection to the cerebellar cortex and to the corticonuclear projection, thus, establishing and extending the detailed micromodular organization of the connections between inferior olive and cerebellum.     

Morphology of the inferior olivary complex of the rhesus monkey (Macaca mulatta)

The morphology of the inferior olivary complex was determined in the rhesus monkey (Macaca mulatta). The position, configuration, and relations of each of its components were ascertained in serial transverse sections extending from caudal through rostral poles of the complex. The medial accessory nucleus was divided into seven cell groups (labeled a through g). The principal nucleus consisted of well-developed dorsal, ventral, and lateral lamellae and a criterion was established for distinguishing the boundaries of each. This distinction was based upon the pattern of invagination that developed in the principal nucleus in progressing rostrally from its caudal pole. The dorsal and lateral lamellae each presented a characteristic pattern of major invaginations, while the ventral lamella did not. Finally, a detailed comparison was made of the inferior olivary complex of the monkey with that of the cat as determined by other investigators. It was shown that the medial and dorsal accessory nuclei of the two species appeared similar and that the major difference between these species concerns the principal nucleus.