Medial Nucleus Of Cerebellum


The present review summarizes and discusses the morphology of five central excitatory synapses that are quantitatively well described: (1) a giant synapse, the so-called Calyx of Held, in the medial nucleus of the trapezoid body in the auditory brain stem, (2) the mossy fiber terminal establishing synapses with multiple cerebellar granule cell dendrites, (3) the mossy fiber bouton in the hippocampus predominantly terminating on proximal dendrites of CA3 pyramidal neurons, (4) the climbing fiber-Purkinje cell synapse in the cerebellum, and (5) cortical input synapses on the basal dendrites of layer 5 pyramidal cells.  

Similar specializations with pronounced coclustering of the Kv4.2 and 4.3 subunits were observed between nerve cells in the medial nucleus of the habenula.  

There were focal dense regions of fibers immunoreactive to calbindin in the medial and inferior nuclei, with an especially dense region of label at the border of the medial nucleus and the nucleus prepositus hypoglossi.  

Kv3.1 is expressed in a tonotopic gradient within the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem, where Kv3.1 levels are highest at the medial end, which corresponds to high auditory frequencies.  

NA application depressed the neuronal firing rate more in the medial nucleus (MN) than in the interpositus (IN) and in the lateral nucleus (LN).  

In RMN, many neurons exhibited definite alpha(1A) subunit-staining in the medial nucleus, interposed nucleus, and lateral nucleus of deep cerebellar nuclei.  

A signal for the short PDE4A1 isoform was found in regions in which the two long isoforms were both expressed, with the exception of the medial nucleus of the amygdala where weak signals for PDE4A5 and PDE4A10 were detected but PDE4A1 was absent.  

After localized injection of BDA into the Mx, labeled CT axons were found ipsilaterally in the thalamic reticular nucleus (TRN), the ventroanterior-ventrolateral complex (VA-VL), the central lateral nucleus (CL), the central medial nucleus, and the centromedian nucleus, but with the primary focus in the VA-VL.  

Labeled terminals of uncrossed projections were seen in the middle, dorsal, and ventrolateral parts of the middle subdivision and in the ventral part of the caudomedial subdivision of the medial nucleus. The terminals of crossed projections from the CCN were distributed ventrally in medial to ventrolateral parts of the middle subdivision of the medial nucleus. Some terminals were seen in the caudomedial subdivision of the medial nucleus.  

In Purkinje cell degeneration, subunit transcripts decreased below control levels in olivary neurons; however, alpha1, beta2, and gamma2 transcript levels were slightly increased in the medial nucleus of the deep cerebellar nuclei.  

Labeled thalamocortical neurons overlapped cerebellar inputs in the VLd and VApc and overlapped pallidal inputs in the VLa and the ventral medial nucleus.  

The 1.5-kb 5'-upstream region drove reporter gene expression in the olfactory bulb, dorsal cortex and hippocampus, while the regulatory element for the expression in the amygdaloid nucleus, septum, habenula medial nucleus, choroid plexus, substantia nigra, inferior colliculus, pontine nucleus and cerebellum was located in the 5'-upstream sequence between 1.5 kb and 6.3 kb.  

In the medial nucleus, labeled terminals were distributed in medial, ventral, and ventrolateral parts of the middle subdivision and ventral parts of the caudomedial subdivision.  

Labeled terminals were bilaterally seen in the medial nucleus and the anterior and posterior interpositus nucleus. In the medial nucleus, labeled terminals were seen in limited rostromedial parts of the middle and the caudomedial subdivision. The present study shows that the spinocerebellar fibers originating from the lowest lumbar and sacral-caudal segments project to specific areas of the anterior interpositus and the medial nucleus.  

In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus.  

Labeled axons entered the medial nucleus from its rostromedial aspect and terminated widely in medial and ventral parts of the middle subdivision.  

Labeled terminals were distributed to dorsal and medial parts of the middle subdivision at its rostral levels and to medial parts of the caudomedial subdivision of the medial nucleus. Single axons were seen to course rostrocaudally in the medial nucleus and give off terminal axons to both subdivisions. A few labeled terminals were seen in the dorsolateral protuberance of the medial nucleus, and in the anterior interpositus and the posterior interpositus nuclei. The present study demonstrates that spinocerebellar neurons in laminae VI and VII of the cervical enlargement project to dorsomedial areas of the medial nucleus at rostral levels, bilaterally but predominantly ipsilaterally.  

The prearcuate cortex projects to several brainstem areas which also receive projections from the caudal fastigial nucleus, including the supraoculomotor periaqueductal gray matter, superior colliculus, medial nucleus reticularis tegmenti pontis, dorsomedial basilar pontine nucleus, dorsolateral basilar pontine nucleus, nucleus reticularis pontis caudalis, pontine raphe, and nucleus prepositus hypoglossi.  

Retrograde transport of lectin-conjugated horseradish peroxidase and Fluoro-Gold was used in an attempt to obtain data to confirm the existence, predicted from physiological studies, of a direct, monosynaptic projection from the medial nucleus of the cerebellum (MN) to the paraventricular nucleus of the hypothalamus (PVH) in the rat. However, injections confined to the PVH and regions of the hypothalamus adjacent to it, or to the PVH alone, produced no retrograde neuronal labeling in the medial nucleus, indicating that the MN does not project directly to the PVH.  

In the vestibular nuclei complex the location of the tertiary branches of various end-organs exhibited considerable overlap within the major vestibular nuclei (SN, superior nucleus; LN, lateral nucleus; MN, medial nucleus; DN, descending nucleus).  

Most neurons were in the caudal half of the descending vestibular nucleus, the remainder at corresponding levels of the medial nucleus or the medial-descending border.  

In addition, sensory regions of the forebrain and brain stem (e.g., nucleus gracilis and ventral posterior medial nucleus of the thalamus) had a lower basal metabolic rate than control animals.  

Labeled terminals were distributed from the medial to the ventrolateral part of the middle subdivision of the medial nucleus throughout its rostrocaudal extent. Labeled terminals were also seen in the lateral part of the medial nucleus and in the border region between the medial nucleus and the interpositus nuclei, which corresponds to the rostromedial extension of the posterior interpositus nucleus. No labeled terminals were seen in the caudomedial subdivision and the dorsolateral protuberance of the medial nucleus, the dorsolateral hump region and the lateral nucleus.  

The pathway arises from all four cerebellar nuclei on the contralateral side; mainly from the posterior interpositus nucleus and lateral nucleus and to a lesser extent from the medial nucleus and anterior interpositus nucleus. The fibers arising from the medial nucleus and the posterior interpositus nucleus terminate mainly in the deeper zone of layer IV and in layer VI throughout the entire rostrocaudal extent of the contralateral superior colliculus.  

Terminals from the posterior interposed nucleus were located slightly rostral and lateral to those from the lateral nucleus, mainly around the border between the ventral lateral nucleus and the ventral posterior medial nucleus.  

In addition, the medial nucleus receives projections from the superior central nucleus, the nucleus raphe obscurus, the nucleus raphe magnus, and the periolivary reticular formation.  

After HRP injection confined to the rostral half of the lateral valvula, labeled neurons were also found ipsilaterally in the octavolateral and trigeminal cell groups: the eminentia granularis, the medial nucleus of the octavolateralis column, and the isthmic primary sensory trigeminal nucleus. On the other hand, the lateral valvula receives vestibular and lateral line inputs indirectly, via the eminentia granularis and the medial nucleus of the octavolateralis column, respectively..  

On the other hand, non-dopaminergic fibers projecting from the ventral tegmental area to the deep cerebellar nuclei were seen to terminate mainly in the lateral nucleus, to a lesser extent in the interpositus nucleus, but not at all in the medial nucleus.  

Cells in the medial nucleus of the mutant rats had significantly increased spontaneous firing rates in comparison with cells from normal rats. There was no reliable change in the average firing rate or rhythmicity of cells in the medial nucleus of the dystonic rats, although previous studies have shown that harmaline activates neurons in the inferior olive in the mutants.  

Puncta density was decreased in the medial nucleus only in 25-day-old dt rats in comparisons with normal littermates.  

The afferent projection to the lateral part of the eminentia granularis is more dense than the projection to the medial nucleus, as shown by image processing of the HRP labeling.  

The largest group of labelled neurons (811 +/- 65) constituted a neuronal band located contralaterally in the medial nucleus and rostral part of the descending nucleus.  

In cerebellum, F1/GAP-43 hybridization was detected in granule cells but not Purkinje cells; in olfactory bulb, mitral cells but not internal granule cells; in habenula, cells in the lateral but not medial nucleus; in substantia nigra, pars compacta cells but not cells in pars reticulata.  

Injection of horseradish peroxidase (HRP) into the parvocellular reticular formation resulted in labeled neurons in the dorsolateral protuberance of the contralateral medial nucleus and bilaterally in the dorsolateral hump region and the large celled subgroup of the lateral nucleus. A small number of labelled cells were found in the middle part of the contralateral medial nucleus. No labeled neurons were observed in the caudomedial portion of the medial nucleus or the small-celled region of the lateral nucleus..  

Immunoreactive terminal axons and terminals were distributed in the medial nucleus, and the anterior interpositus and the posterior interpositus nucleus.  

Using immunocytochemical methods, both calbindin and GABA were found to be colocalized in the somas of all the cells of the medial nucleus of the trapezoid body (NMTB) of the rat auditory system.  

For example, the medial nucleus of the inferior olive and most cerebellar nuclei contained diffuse non-fibrillar receptor immunoreactivity.  

In the cerebellar nuclei, portions of the medial nucleus and magnocellular portion of the lateral nucleus had moderately dense networks of immunoreactive fibers, whereas loose networks of fibers were observed in the posterior interposed nucleus.  

The medial portion of the tuber vermis projects to the dorsal part of the caudomedial subdivision of the medial cerebellar nucleus (MNcm), whereas the lateral portion of the tuber vermis projects to the dorsal part of the MNcm and the caudal part of the middle subdivision of the medial nucleus.  

The cerebellar nuclei, especially medial nucleus, were stimulated electrically and the induced eye movements were observed. The horizontal nystagmus towards the ipsilateral to the stimulated side was observed when the caudal portion of the medial nucleus was stimulated. On the other hand, the horizontal nystagmus towards the contralateral to the stimulated side was observed when the rostral portion of the medial nucleus was stimulated.  

The specific staining was also found in some other CNS structures, including brain-stem reticular formation; amygdala; medial nucleus of inferior olive but not the rest of inferior olive, external granule cell layer and Purkinje's cells of cerebellum, and deep cerebellar nuclei.  

Moderate binding was found in the lateral caudate-putamen, medial nucleus accumbens, olfactory tubercle, vertical and horizontal diagonal bands of Broca, and basolateral amygdala.  

However, some preferential distribution of the contralateral projections to the ventral medial nucleus appears to exist. The ventral medial nucleus receives bilateral input from the fastigial nucleus which originates from about one quarter of the thalamus projecting neurons in this nucleus. Of all other cerebellar nuclei only the dentate nucleus projects to the ventral medial nucleus and this projection is exclusively contralateral..  

Anterior lateral line nerve afferents terminate throughout the neuropil of the electroreceptive dorsal nucleus and in the lateral neuropil of the mechanoreceptive medial nucleus. Primary afferents in the posterior lateral line nerve project to the medial neuropil of the ipsilateral medial nucleus, continue rostrally into the cerebellum and cross to the central neuropil of the contralateral medial nucleus.  

The main stages of neuronal dendritic differentiation occur between E16 and E20, indicating that the ingrowth of afferent in puts to the medial nucleus most probably occurs rather early and is concomitant with dendritic development..  

More rostrally at the level of the superior colliculus, terminal fields are found in the medial nucleus of the medial geniculate body, the suprageniculate, pretectal, and mesencephalic reticular nuclei, marking the end of the LAC.  

Responses of neurons in the medial nucleus of cerebellum (CBM) were studied on stimulation of ipsilateral and contralateral homonymous muscles, in decerebrated cats.  

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.  

For example, in the medial nucleus the sites of origin of fibers to the flocculus and uvula are different.  

In the thalamus, AII-stained cells were found in the paraventricular nucleus, the central medial nucleus, the nucleus reuniens, and rostral parts of the zona incerta. Two cell groups in the basal telencephalon, in the dorsal part of the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala, lay at either end of an AII-stained pathway coursing through the stria terminalis.  

Furthermore, double labeling revealed neurons in both cerebellar nuclei (especially the medial nucleus) that project to both the mesencephalon and the cervical spinal cord.  

Labeled cells were occasionally seen in the medial mammillary nucleus (parafloccular cases) and among fascicles of the mammillothalamic tract (all posterior lobe cases) immediately above the medial nucleus.  

Further, this projection also supplies input to the medial nucleus of the periaqueductal gray matter, bilaterally in the rabbit and rat, and in the rabbit also to the ipsilateral superior and lateral vestibular nuclei.  

The present results, taken in conjunction with data on the embryogenesis of the rat IOC, suggest that the avian dorsal lamella represents, from lateral to medial, the dorsal olivary nucleus, the principal olivary nucleus, and the rostral and a small part of the caudal medial nucleus (MO) of mammals, while the ventral lamella represents a larger part of the caudal MO of mammals..  

In the pontine gray, the bulk of the projection concerns the dorsal aspect of the medial nucleus.  

The results showed that the cerebello-tectal projections arise from two different regions of the cerebellar nuclei: the caudal half of the medial nucleus and the ventrolateral part of the posterior interposed nucleus. Fibers arising from the medial nucleus distribute bilaterally in the superficial zone of the intermediate gray layer in the superior colliculus, while those originating from the posterior interposed nucleus terminate contralaterally in the deeper aspect of the intermediate gray layer and in the deep gray and white layers.  

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.  

Many of the neurons in the lateral, the interpositus as well as the caudal half of the medial nucleus project to the diencephalon. in the medial part of the interpositus nucleus and the adjoining part of the medial nucleus, distribute divergent axon collaterals to the diencephalon and the spinal cord.  

Lesions in the cerebellar cortex of the anterior lobe and in anterior parts of the posterior lobe result in terminal degeneration, mainly in the nucleus Deiters dorsalis, but also scantily, in peripheral regions of the superior nucleus, the nucleus Deiters ventralis, the ventrolateral part of the medial nucleus and, mainly medially, in the descending nucleus. Lesions in the medial cerebellar nucleus result in degeneration bilaterally in the vestibular complex, most heavily affecting the nucleus Deiters ventralis and cell group B, but also affecting peripheral regions of the superior nucleus, the medial nucleus- mainly in dorsomedial regions, lateral and caudal parts of the descending nucleus and, very scantily, in the nucleus Deiters dorsalis.  

In addition, the localization of ELI-containing perikarya is reported for the first time in the following areas: the olfactory bulb, the olfactory tubercle, the lateral preoptic nucleus, several nuclei within the amygdaloid nuclear complex, the hippocampus, the neocortex, the cingulate cortex, the posterior mammillary nucleus, the medial nucleus of the optic tract, the brachium of the inferior colliculus, the ventral tegmental nucleus, the locus ceruleus, the sub-ceruleal region, the lateral trapezoid nucleus, the nucleus reticularis lateralis, and lamina VII of the cervical spinal cord.  

Double-labeled cells were more numerous in the caudal part of the medial nucleus than in the other cerebellar nuclei.  

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. 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.  

Both sets of data indicate that several neurons in the medial nucleus, which project to mesencephalon and thalamus, also distribute collaterals to medulla oblongata and spinal cord. These branching neurons were principally located in the caudal and intermediate portions of the medial nucleus. The electrophysiological data in addition indicate that the branching point of the neurons in the medial nucleus is located relatively close to the cell soma.  

About 17% of these responding neurons received monosynaptic excitation, most frequently from the rostral medial nucleus.  

In the medial nucleus (M) labeled neurons were distributed in the central to the caudal portions, and there was a conspicuous group of labeled small neurons extending from the ventrolateral part to the intermediate zone between the M and the anterior interpositus nucleus.  

Axons from the cerebellar cortex distribute mainly to vestibular areas which receive no primary afferent projections, e.g., the dorsal part of the lateral vestibular nucleus, the dorsolateral margin of the inferior vestibular nucleus as well as cell groups comparable to "f" and "x." In contrast, fastigial fibers show considerable overlap with primary vestibular input, particularly in the ventral part of the lateral nucleus, the central part of the inferior nucleus and the medial nucleus. In Part I of our study we have shown that the major targets of primary vestibular fibers are the central part of the superior nucleus, a portion of the parabrachial complex possibly comparable to subnucleus "y"," the ventral part of the lateral nucleus and the medial nucleus. The ventral part of the lateral nucleus, and perhaps the medial nucleus, also relay to the spinal cord.  

In the ipsilateral nuclei strong projections were found to rostral portions of the medial nucleus (M) and the caudal two thirds of the anterior interpositus nucleus (IA) with predominance in the lateral part of the latter.  

The vestibular nerve fibers were found to terminate within central regions of the superior nucleus, in the cell group A, the nucleus Deiters ventralis, the nucleus tangentialis, the cell group B, the dorsomedial part of the medial nucleus and the descending nucleus.  

The medial nucleus contains three major subdivisions (labelled a, b, c after Bowman and Sladek, '73) and a group of neurons which is comparable to the cap of Kooy.  


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