Contralateral Cerebellar Nuclei Research Articles

The relationship between MI and SMA afferents and cerebellar and pallidal efferents in the macaque monkey

The purpose of the present study was to determine the interrelationship between the thalamic afferents arising from the cerebellum (Cb) and the internal segment of the globus pallidus (GPi) with the neurons projecting to the primary motor cortex (MI) and to the supplementary motor area (SMA). We combined fluorescent retrograde tracers with a double anterograde labeling technique. Multiple injections of a combination of Diamidino Yellow and Fast Blue were made into either the MI or SMA hand/arm representation as determined by intracortical microstimulation. In the same animal, biotinylated dextran amine was injected into the GPi and horseradish peroxidase conjugated to wheat germ agglutinin was injected into the contralateral cerebellar nuclei. The results revealed that the cerebellar and pallidal thalamic territories are largely separate. The ventral anterior nucleus (VA) and the ventral lateral nucleus pars oralis (VLo) contained a greater density of pallidal labeling while a greater density of cerebellar label was observed more caudally in the ventral posterior lateral nucleus pars oralis (VPLo) as well as in nucleus X (X). Moreover, we observed that the greatest coincidence of retrograde cell labeling was within the pallidal thalamic territory following the SMA injections and within the cerebellar thalamic territory following the MI injections. However, interdigitating foci of pallidal and cerebellar label were also observed particularly in the ventral lateral nucleus pars oralis (VLo) and the ventral lateral nucleus pars caudalis (VLc). In both VLo and VLc, we additionally observed coincidence between the cerebellar labeling and SMA projection neurons as well as between pallidal labeling and MI projection neurons. These data suggest that while MI primarily receives inputs originating from Cb and SMA primarily receives inputs originating from GPi, it also appears that MI and SMA receive secondary afferents arising from GPi and Cb, respectively.

Segregation of cerebrorubral and cerebellorubral synaptic inputs on rubrospinal neurons of fetal cats as demonstrated by intracellular recording

Cerebrorubral and cerebellorubral inputs are localized to distal dendrites and somata of red nucleus neurons in adult cats, respectively. To examine if this segregation is established early in development, we performed intracellular recording from rubrospinal neurons of fetal cats aged from embryonic day 58 to 65. Stimulation of the contralateral cerebellar nuclei evoked excitatory postsynaptic potentials (EPSPs). EPSPs were also induced by stimulation of the ipsilateral pericruciate cortex but they were much slower in time course and smaller in amplitude compared to cerebellar ones. We suggest that cerebrorubral and cerebellorubral synapses are segregated on soma-dendritic membrane of rubrospinal neurons early in development.

Distribution of cerebellothalamic and nigrothalamic projections in the dog: a double anterograde tracing study.

The distribution of nigrothalamic and cerebellothalamic projections was investigated in the dog by a double labeling strategy combining the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and tritiated amino acids. Following tritiated amino acid injections into the substantia nigra pars reticulata (SNr) and WGA-HRP injections into the contralateral cerebellar nuclei, we found that the nigrothalamic and cerebellothalamic afferents distribute to three main targets: the central portion of the ventral anterior nucleus (VA) and the ventral lateral nucleus (VL), the internal medullary lamina (IML) region, which includes the paralaminar VA, the mediodorsal nucleus (MD) and the central lateral nucleus (CL), and finally the ventromedial nucleus (VM). We observed three distribution patterns of labeled fibers: a) Dense single label was observed in the central portion of VA following the SNr injections and in VL following the cerebellar nuclei injections. b) A complementary pattern consisting of alternating foci of nigral and cerebellar label was found in the IML region. This pattern was also observed in the caudal intralaminar nuclei where cerebellar label predominated in the centrum medianum (CM), while the parafascicular nucleus (Pf) primarily contained nigral label. c) An overlapping pattern of autoradiographic and WGA-HRP label was found in the lateral half of the VM. Overall, the distribution of nigrothalamic and cerebellothalamic projections was widespread throughout much of rostrocaudal thalamus. However, the pattern of projections varied along a continuum from lateral to medial thalamus. In lateral thalamus, nigral and cerebellar projections distributed to separate nuclei while in medial thalamus, the projection pattern changed to focal and complementary in the IML and overlapping in VM. Taken together, these thalamic projections may constitute crucial links in different functional channels involved in alerting and orienting mechanisms associated with motor behavior. Our findings also suggest that the organization of motor thalamic afferents in the dog shares similarities with the segregated and parallel circuitry characteristic of primates as well as with the overlapping and converging circuits of rodents and other carnivores.

Plastic synaptic reorganization in the sensorimotor cortex of adult cats after lesioning of the contralateral cerebellar nucleus interpositus

Intact cats and animals undergoing lesioning of the contralateral cerebellar nucleus interpositus between one and six months previously were used in this research, employing intracellular recording techniques and investigating the response of corticospinal neurons (CSN) to stimulating the aforementioned nucleus, the ipsilateral cerebellar nucleus interpositus, and the ventrolateral thalamic nucleus. A reduction was found in the stage of rise to peak in monosynaptic thalamocortical EPSP in CSN of operated animals, with a low axonal conduction velocity, pointing to distant terminal dendrosomatic sprouting and formation of new synapses at proximal sections of the CSN somatodendritic membrane. Findings are presented on formation of ipsilateral interpositothalamocortical projections duplicating similar contralateral projections in intact animals. Contralateral cortico-interposital collaterals were found in intact animals and similar sprouting of ipsilateral origin in those which had undergone surgery.

Cerebellar nuclear afferents from the lateral reticular nucleus in the cat

Cerebellar afferent fibers were anterogradely stained throughout their length after injections of horseradish peroxidase labeled wheat germ agglutinin in the lateral reticular nucleus in cats. Most fibers ascended through the ipsilateral restiform body, but a few fibers ran on the contralateral side. Some anterogradely stained fibers crossed the midline in cerebellum. Terminal fibers were present in the granular layer and in the cerebellar nuclei. Plexuses of nuclear terminal fibers were found in the ipsilateral interposed and dentate nuclei and were dense in the former. A smaller number of presumably terminal fibers were observed in the ipsilateral fastigial nucleus and in the contralateral cerebellar nuclei. The findings give further evidence for the lateral reticular nucleus being an important source of cerebellar nuclear afferents.

Inhibitory nigral influence on cerebellar evoked responses in the rat ventromedial thalamic nucleus.

The ventral medial nucleus of the thalamus (VM) has been shown in rats and cats to constitute a common target for nigro- and cerebello-thalamic pathways. In the present study the responses of VM neurons to ipsilateral substantia nigra (SN) and contralateral cerebellar nuclei stimulation were analyzed in the rat. The typical response of VM neurons to SN stimulation consisted of a pure short-latency (1.1-3 ms), short-duration (7-17 ms) IPSP. Latencies of these responses were accorded well with the conduction velocity of the nigro-thalamic fibers as measured on the basis of antidromic activation of this pathway. A high percentage (58%) of the thalamic neurons receiving the inhibitory nigral effect were also affected by cerebellar stimulation. The cerebellar effect consisted of a short-latency depolarizing potential which could trigger an action potential. These responses were invariably blocked during the course of SN evoked inhibition. Such convergence was found with fastigial as well as interpositus/dentatus evoked responses. The demonstration of an interaction between the processing of SN and cerebellar output at thalamic level provides an important clue for the understanding of the neurophysiologic mechanisms by which SN acts on motor behavior.

Cerebellar cortical efferent fibers of the paraflocculus of tree shrew (Tupaia glis).

Efferent projections from the paraflocculus of the tree shrew (Tupaia glis) were studied utilizing the Fink and Heimer ('67) method. Cerebellar corticonuclear fibers of both dorsal (Dpf) and ventral (Vpf) divisions of the paraflocculus terminate in the lateral cerebellar nucelus (NL) and in the posterior interposed nucleus (NIP). These fibers are ipsilateral, topographically organized and arranged into at least two zones. Following injury to either the Dpf or Vpf, degenerated axons are found in lateral and caudal regions of the NIP respectively. Consequently, these two portions of the paraflocculus have relatively exclusive terminal fields with overlap only at the periphery. Preterminal debris is seen in basically similar areas of the NL (caudolateral, caudal, ventral) after damage to either the Dpf or Vpf. This observation leads to the conclusion that the terminal fields for these areas of parafloccular cortex are largely coextensive in the NL. In addition to the topographical representation of the Dpf and Vpf in both the NL and NIP, there is evidence that these corticonuclear fibers are also organized into the general zonal pattern hypothesized by Voogd ('69). Persistent and numerous degenerated axons from both the Dpf and Vpf end in lateral and caudal NIP, respectively, corroborating the presence of a relatively wide zone C2 in both divisions of the paraflocculus. The Dpf and Vpf also project into the NL to a terminal field that appears to consist of two portions. One part located in caudal, ventral and/or caudoventral areas of the NL and a second at slightly more rostral and rostrolateral areas. The presence of a cortical region which is affiliated with two areas of the NL substantiates not only the existence of zone D in the paraflocculus, but gives experimental evidence that it may consist of two parts as previously suggested (Voogd, '69). From the Dpf many fibers enter the NL while few are seen in this nucleus after damage to the Vpf. This suggests that zone D is wider in the Dpf and narrower in the Vpf. The results of this study do not support previous suggestions that the paraflocculus projects to either only the NL or to most of, or all of, the ipsilateral cerebellar nuclei. No projections to any contralateral cerebellar nuclei are seen. There is also no conclusive proof that the parafloccular cortex of Tupaia projects into the vestibular complex or to any other brainstem relay nuclei.

The organisation of the cerebellorubral projection: an experiment study in the rat.

AbstractThe organization, distribution and extent of the cerebellorubral projection in the rat was investigated employing silver impregnation techniques. Cerebellar lesions of varying size were introduced stereotaxically into the deep cerebellar nuclei in a series of 32 rats and the midbrains were stained with the method of Fink and Heimer. Following large lesions which involved all of the cerebellar nuclei and their emerging fibres, numerous degenerating fibres of passage were observed to course within the brachium conjunctivam, to decaussate at the level of the inferior colliculus, and to enter the ventromedical aspect of the contralateral red nucleus. The red nucleus of the rat consists of a caudal magnocellular portion in which giant and large cells predominate and a rstral parvocellular part consisting mainly of small and medium sized cells. Within the red nucleus, coarse preterminal and terminal degeneration was distributed throughout the magnocellular portion, particularly in relation to the cell bodies and proximal dendrites. Degeneration within the parvocellular part of the nucleus was less abundant, finer in calibre and was parvocellular part of the nucleus was less abundant, finer in calibre and was scattered throughout the neuropil. Following discrete lesions of the nucleus interpositus, preterminal and terminal degeneration was restricted to the magnocellular red nucleus and it was similar in calibre and distribution to that observed in the same area following total lesions. No terminal degeneration was encountered in the parvocellular region at any time following lesions of the nucleus interpositus and only degenerating fibres of passage were seen coursing through the parvocellular region en route to thalamic levels. After lesions restricted to the nucleus lateralis, degenerating fibres were again observed coursing within the brachium conjuctivum and entering the red nucleus. In cases with nucleus lateralis lesions a pattern opposite to that observed following nucleus interpositus lesions was evident. Only passing fibres occurred within the magnocellular region and terminal degeneration was limited to the parvocellular part where it was randomly distributed, moderate in amount and fine in calibre.This investigation has shown that the nucleus in the rat receives a major projection from the contralateral cerebellar nuclei and that a differential distribution of fibres from the nucleus interpositus and the nucleus lateralis terminates within the rubrospinal and rubroolivary portions of the red nucleus respectively.

Afferents to the cerebellar lateral nucleus. Evidence from retrograde transport of horseradish peroxidase after pressure injections through micropipettes.

HRP was injected by pressure from glass capillary micropipettes unilaterally into the lateral nucleus of rat so as to encompass the entire nucleus, but without spread into the interpositus nuclei. The cells of origin of the afferents to the lateral nucleus were studied after retrograde transport of the HRP. The reticulotegmental nucleus of the pons was labelled bilaterally and is the major source of crossed and uncrossed reticular imputs. The pontine nuclei also provide extensive crossed and uncrossed afferents. The inferior olive gives a large crossed olivo-lateral nucleus projection and a minor uncrossed input. The trigeminal nuclear complex--the nucleus of the spinal tract and the mesencephalic, principal sensory, and motor nuclei--all provide uncrossed afferents. The rostral portion of the lateral reticular nucleus gives a small crossed and uncrossed projection while the perihypoglossal nuclei and the dorsal parabrachial body give crossed afferents to the lateral nucleus. The norepinephrine afferent system from the locus coeruleus is represented by one or two heavily labelled cells and the serotonin raphe systems come from at least five raphe subgroups, the dorsal, superior centralis, pontis, obscurus and magnus nuclei. No evidence was found for commissural fibers between ipsilateral or contralateral cerebellar nuclei, or afferent axons from the spinocerebellar nuclei and the paramedian retricular nucleus. The significance of these sources of afferent imputs to the lateral cerebellar nucleus is discussed. The question is raised of the direct relationship between size of terminal axonal arborization and the quantity of HRP granules present in a cell retrograde transport. The limitations of the HRP method for detecting subtle local differences in the distribution of afferents within the heterogeneous groups of neurons in the lateral nucleus are discussed.

Physiopathology of the cerebellum in the monkey: Part 1. 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.

On the organization of cerebellar efferent pathways in the nurse shark (Ginglymostoma cirratum).

AbstractThe organization of the efferent fiber systems of the nurse shark cerebellum was studied with the Nauta and Fink‐Heimer techniques. Lesions of the cerebellar cortex produce a pattern of terminal degeneration restricted to select regions of the cortex, as well as ipsi‐ and contralateral cerebellar nuclei. We found no evidence of cortical axons projecting beyond the nuclei, to the medulla and spinal cord as has often been reported.Lesions involving the cerebellar nucleus reveal three efferent pathways. The ipsilateral descending cerebello‐bulbar (IDC) pathway extends as far caudal as the first spinal segment and issues fibers to the lateral parts of the reticular formation. The brachium conjunctivum splits into a larger ascending limb (BCA) and a smaller descending one (BCD). The latter descends to the caudal medulla terminating along its course in the medial reticular formation. The ascending limb provides an input to (1) a nucleus we have tentatively labelled the “red nucleus,” (2) the trochlear nucleus, (3) the oculomotor nuclei, (4) the midbrain central gray, and (5) a poorly differentiated nucleus in the dorsal thalamus.