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.     

The anatomical organization of the cerebello-olivary projection in the cat.

The cerebello-olivary pathway in the cat has been examined using orthograde and retrograde neuroanatomical tracing techniques. The orthograde transport of 3H-leucine from injection sites in the deep cerebellar nuclei labeled dentate and interpositus projections to the rostral two-thirds of the contralateral inferior olivary complex. These projections are topographically organized, with the dentate nucleus projecting to the principal olivary nucleus and the posterior and anterior interpositus nuclei projecting to the medial and dorsal accessory olives respectively. Fibers from the ventral half of the dentate nucleus terminate in the lateral bend and ventral lamina of the principal olive, whereas the medial and lateral parts of the dorsal half of the nucleus project to the medial and lateral regions of the dorsal lamina respectively. It is apparent that the more caudal parts of the interpositus nuclei project to areas of the medial and dorsal accessory olives near the caudal end of the principal olivary nucleus, whereas neurons in the more rostral parts of the interpositus nuclei project to the more rostral areas of the accessory olivary nuclei. A connection between the fastigial ncleus and the inferior olive could not be demonstrated. The retrograde transport of horseradish peroxidase (HRP) from injections sites in the inferior olive labeled cells throughout the contralateral dentate and interpositus nuclei. The labeled cells were especially numerous in the ventral parts of the dentate and posterior interpositus nlclei. These HRP-positive neurons were consistently small (10--15 mu) ovoid or spindle-shaped cells, with relatively large nuclei and light-staining Nissl substance. This evidence strongly suggests that the cerebello-olivary pathway originates from a population of small neurons in the dentate and interpositus nuclei and projects to specific, topographically defined areas in the contralateral inferior 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.     

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.     

Vestibular afferents of the inferior olive and the vestibulo-olivo-cerebellar climbing fiber pathway to the flocculus in the cat

The projection of the vestibular nuclei to the inferior olive was investigated by means of anterograde transport of tritiated leucine. Following injections in the medial and descending vestibular nuclei, terminal labeling was found ipsilaterally in the dorsomedial cell column, subnucleus beta and the caudal medial accessory olive, while the latter also received afferents from the nucleus prepositus hypoglossi. At the contralateral side termination in the dorsomedial cell column and the medial accessory olive was found after injections in the nucleus vestibularis superior and group Y. The ventrolateral outgrowth and different parts of the principal olive also received afferents from these two nuclei and also from ventral parts of the lateral cerebellar nucleus. The dorsal cap was labeled exclusively from the contralateral nucleus prepositus hypoglossi. The termination in the inferior olive of the vestibular afferents is compared with the projection from a number of pretectal nuclei. Furthermore the consequences of the divergence and convergence of both types of projections at the level of the inferior olive is discussed in relation to the subsequent climbing fiber projection to the flocculus.     

The dorsal column nuclear projections to the nucleus ventralis posterior lateralis thalami and the inferior olive in the cat: an autoradiographic study.

This autoradiographic study demonstrates a topical projection of the dorsal column nuclei to the contralateral nucleus ventralis posterior lateralis thalami and the accessory part of the inferior olive. In contrast to earlier anatomical studies the projections of the gracile nucleus and the internal cuneate nucleus proved to be independent and entirely contralateral. Fibers from the gracile nucleus terminate only in the lateral part of the nucleus ventralis posterior lateralis (VPL1) and from the internal cuneate nucleus only in the medial part of this nucleus (VPLm). Projections of the gracile nucleus to the contralateral inferior olive are restricted to the caudal one-third of the medial accessory olive and the ventrolateral part of the dorsal accessory olive. The internal cuneate nucleus is only connected with the dorsomedial part of the rostral two-thrids of the dorsal accessory olive. Our material does not allow conclusions about projections from the dorsal column nuclei to other thalamic nuclei and about rostrocaudal point to point relationships between the dorsal column nuclei and the thalamus or the inferior olive.     

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.     

Somatosensory Trigeminal Projections to the Inferior Olive,Cerebellum and other Precerebellar Nuclei in Rabbits

We have analysed the pathways through which somatosensory information from the face reaches the inferior olive and the cerebellum in rabbits. We used wheatgerm agglutinin - horseradish peroxidase (WGA-HRP) to trace projections from all parts of the somatosensory trigeminal system to the olive, cerebellar cortex, the cerebellar deep nuclei and the pontine nuclei. Projections to the cerebellar cortex and inferior olive were verified using retrograde transport of WGA-HRP. Two regions of the inferior olive–the medial dorsal accessory olive and the ventral leaf of the principal olive–receive inputs from pars interpolaris (Vi) and rostral pars caudalis (Vc) of the spinal trigeminal nucleus and from the principal trigeminal nucleus (Vp). Another area in the caudal medial accessory olive receives inputs from rostral Vo (pars oralis of the spinal trigeminal nucleus), caudal Vi and Vc. There are trigemino-olivo-cortical inputs to lobule HVI via all these olivary areas and to the paramedian lobe via the principal olive only. Cerebellar cortex–lobules HVI, crus I and II, paramedian lobe and IX–receives direct mossy fibre inputs from Vp, Vo and rostral Vi. The pontine nuclei receive an input only from rostral Vi. We saw no trigeminal projections to other precerebellar nuclei or to the deep cerebellar nuclei. The concentration of face somatosensory cortical inputs, via several pathways, upon lobule HVI may underlie its important role in the regulation of learned and unlearned eyeblinks.     

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.     

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.     

Axonal branching of the olivocerebellar projection in the rat: a double-labeling study

Collateralization of olivocerebellar (climbing) fibers was studied in the rat by means of the fluorochrome double-labeling technique. Most of the olivocerebellar projection is crossed except for a minimal ipsilateral component which arises from the most rostal part of the inferior olivary nucleus (ION). ION neurons in the caudolateral part of the medial accessory olive (MAO) and the dorsal accessory olive (DAO) give off axons that branch to supply both hindlimb areas of the contralateral cerebellar cortex, i.e., the rostral anterior lobe and the caudal paramedian lobule. In addition, neurons in the middle one-third of the contralateral MAO and DAO send axons that divide to terminate in both the caudal part of the anterior lobe and the rostral part of the paramedian lobule (forelimb receiving areas). Neurons within the caudal part of the MAO, the lateral part of the DAO, the ventral lamella of the principal olive (PO), and the dorsomedial cell column (DMCC) send axonal branches that terminate within at least two different areas of the same sagittal zones throughout the contralateral cerebellar cortex. Thus, the ION contains specialized cells that provide a divergence of integrated information from the ION to at least two cerebellar regions.     

HRP study of the organization of auditory afferents ascending to central nucleus of inferior colliculus in cat

The ascending auditory projections to central nucleus of inferior colliculus its ventrolateral and dorsomedial subdivisions (IC_VI, and IC_DM) have been studied in cat using both pressure and electrophoretic injections of horseradish peroxidase (HRP). The results indicate that the predominant ascending projections to inferior colliculus orginate in (1) contralateral cochlear nucleus, (2) contralateral and ipsilateral lateral superior olive, (3) ipsilateral medial superior olive, (4) ipsilateral ventral nucleus of the lateral lemniscus, (5) ipsilateral and contralateral dorsal nucleus of the lateral lemniscus, and (6) contralateral inferior colliculus. In addition, ipsilateral cochlear nucleus, ipsilateral and contralateral intermediate nucleus of the lateral lemniscus, ipsilateral, and to a lesser extent contralateral, periolivary nuclei project to inferior colliculus. Of these nuclei, the lateral superior olive projects exclusively to IC_VL and ipsilateral cochlear nucleus and contralateral inferior colliculus project mostly, if not exclusively, to IC_DM. Many of these projections demonstrate a cochleotopic organization and frequently a nucleotopic organization as well. A cochleotopic organization of the projections is apparent for cochlear nucleus and superior olivary complex. A nucleotopic organization suggests that the heaviest terminations of contralateral inferior colliculus are medial and dorsal in inferior colliculus, of medial superior olive are dorsal and lateral, of superior olivary complex are rostral, of cochlear nucleus are caudal, and of ventral nucleus of the lateral leminiscus are caudal.     

Zonal organization of climbing fiber projections to the uvula in the cat

Climbing fiber projections from the inferior olive to the uvula of the cerebellum were studied in the cat by using retrograde axonal transport of horseradish peroxidase. Following large and small injections into various parts of the uvula, the distribution of labeled cells in the inferior olive was investigated. The findings indicate six longitudinal zones extending throughout the dorsal and ventral uvula: the caudal part of the nucleus beta projects to a most medially located zone (caudal beta zone) with a width of about 0.4 mm; the rostral part of the nucleus beta projects to a zone located at about 0.6 mm from the midline (rostral beta zone); the caudal part of the medial accessory olive (MAO) projects to a zone (caudal MAO zone) located lateral to the rostral beta zone; the dorsomedial cell column projects to a zone (dorsomedial cell column zone) located in the intermediate part of the uvula at about 1.2 mm from the lateral edge of the uvula; the ventral lamella of the principal olive (PO) projects to a zone (ventral lamella of PO zone) about 0.7 mm from the lateral edge of the uvula; finally, the rostral part of the MAO projects to the most lateral zone (rostral MAO zone). These conclusions are in general agreement with those of earlier studies and also provide a more detailed zonal configuration of climbing fiber projections to the uvula.     

The organization of olivo-cerebellar projections in the opossum, Didelphis virginiana, as revealed by the retrograde transport of horseradish peroxidase

The retrograde transport of horseradish peroxidase was utilized to map olivo-cerebellar projections in the Virginia opossum. The spinal cerebellum (anterior lobe, paramedian lobule and pyramis) receives input from several separate regions in the dorsal accessory nucleus, the medial accessory nucleus and portions of the principal nucleus. Evidence is present for a topographical organization whereby specific regions of the olive project to restricted longitudinal zones. The visual-auditory region of the posterior vermis receives input from small areas within the caudal part of the medial accessory nucleus. From a distinctly separate region of the caudal medial accessory nucleus (as well as the principal nucleus), axons project to the uvula. The vestibulo-cerebellum is the recipient of axons from the cap of Kooy and from two spatially separate regions of the medial accessory nucleus. The cerebellar hemisphere (Crus I and II, lobus simplex) is the target of axons from parts of all three olivary nuclei and it is possible that the projections from the different nuclei are targeted upon separate zones. The paraflocculus was found to receive an input from the rostral part of the medial accessory nucleus and from the principal nucleus. The present results suggest that a distinct olivary region may project to several widely separate areas of the cerebellum, and that one cerebellar region may receive input from several areas of the olive. The organization of the olivocerebellar projection is highly complex, but when considered in light of known inputs to the olive, certain patterns emerge.     

The structure and connections of the developing inferior olivary nucleus of the rhesus monkey (Macaca mulatta)

Structural and morphological changes were examined in the inferior olivary complex of 25 rhesus monkeys that were 60 days gestation to three months after parturition. At different ages, one-half brain stem was sectioned sagittaly, and when possible the symmetrical half was sectioned in either the coronal or the horizontal plane. Serial sections were stained by the silver reduction method of Stotler ('51). The olivary complex undergoes its major development between 60 and 129 days gestation when its length, cellular morphology, and afferent patterns resemble those of the adult organ. Structurally, the three major divisions—the principal nucleus, the dorsal accessory nucleus, and the medial accessory nucleus—can be identified at 60 days gestation. At that time, the medial accessory nucleus, the largest of the three, can be subdivided into a ventrolateral and a dorsomedial section; as it develops, it extends caudally and acquires a small cap of cells on its dorsomedial part. By 80 days, the dorsal lamella of the principal nucleus, initially smaller than the ventral, equals the ventral lamella in size and continues to enlarge until by 100 days it has developed two large sulci. The dorsal accessory nucleus, the smallest of the three divisions, initially has a distinct connection with the caudal part of the dorsal lamella of the principal nucleus but it is lost by 92 days. Major afferents to the inferior olive could easily be identified in the early fetal tissue—before the development of the dense neuropil. Afferents first arise from the lateral funiculus of the spinal cord at 60 days and project primarily onto the ventrolateral part of the medial accessory. As they develop, they gradually project more rostrally along the ventrolateral section, onto the dorsomedial section of the medial accessory, onto the caudal part of the ventral lamella, and along the caudomedial part of the dorsal accessory. At 92 days gestation the central tegmental fasciculus, most of which originates from the red nucleus projects into the rostral and later into the middle section of the dorsal lamella, into the rostral ventral lamella, and a few into the rostrolateral part of the dorsal accessory and to the rostral third of the medial accessory. A few fibers arising from the corticospinal tract enter the caudal section of medial accessory, and a few fibers project vertically from the dorsomedial tegmental region of the medulla into the medial section of the dorsal accessory.     

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.     

An autoradiographic study of the cerebellopontine projections from the interposed and lateral cerebellar nuclei in the rat

The projections from the cerebellar lateral and interposed nuclei onto the basilar pontine gray and nucleus reticularis tegmenti pontis (NRTP) have been studied in the rat by the use of the autoradiographic technique. Projections from both nuclei are mainly contralateral. Fibers from the lateral nucleus cover most of the NRTP, except its medial, parvocellular portion. In the pontine gray proper, fibers from the lateral nucleus are distributed to three rostrocaudally oriented columns: (i) in the medial nucleus, (ii) in the ventral nucleus, and (iii) in the dorsolateral and lateral nuclei. The projection is topographically arranged, so that caudal parts of the lateral cerebellar nucleus tend to project to more rostral regions than rostral parts of the lateral nucleus. The interposed nucleus gives rise to a sparser projection, apparently limited to the ventral NRTP and immediate peripeduncular zones. The functional implications of these results are discussed, with particular emphasis on the convergence of corticopontine afferents to the pontine regions involved, and on the reciprocal pontocerebellar pathways from these same regions.     

Projections of the lateral terminal accessory optic nucleus of the common marmoset (Callithrix jacchus)

The connections of the lateral terminal nucleus (LTN) of the accessory optic system (AOS) of the marmoset monkey were studied with anterograde ³H-amino acid light autoradiography and horseradish peroxidase retrograde labeling techniques. Results show a first and largest LTN projection to the pretectal and AOS nuclei including the ipsilateral nucleus of the optic tract, dorsal terminal nucleus, and interstitial nucleus of the superior fasciculus (posterior fibers); smaller contralateral projections are to the olivary pretectal nucleus, dorsal terminal nucleus, and LTN. A second, mejor bundle produces moderate-to-heavy labeling in all ipsilateral, accessory oculornotor nuclei (nucleus of posterior commissure, interstitial nucleus of Cajal, nucleus of Darkschewitsch) and nucleus of Bechterew; some of the fibers are distributed above the caudal oculomotor complex within the supraoculornotor periaqueductal gray. A third projection is ipsilateral to the pontine and mesencephalic reticular formations, nucleus reticularis tegmenti pontis and basilar pontine complex (dorsolateral nucleus only), dorsal parts of the medial terminal accessory optic nucleus, ventral tegmental area of Tsai, and rostral interstitial nucleus of the medial longitudinal fasciculus. Lastly, there are two long descending bundles: (1) one travels within the medial longitudinal fasciculus to terminate in the dorsal cap (ipsilateral > > contralateral) and medial accessory olive (ipsilateral only) of the inferior olivary complex. (2) The second soon splits, sending axons within the ipsilateral and contralateral brachium conjunctivum and is distributed to the superior and medial vestibular nuclei. The present findings are in general agreement with the documented connections of LTN with brainstem oculomotor centers in other species. In addition, there are unique connections in marmoset monkey that may have developed to serve the more complex oculomotor behavior of nonhuman primates. © 1995 Wiley-Liss, Inc.