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.     

Projections of the central cerebellar nuclei to the intralaminar thalamic nuclei in cats

Projections of the central cerebellar nuclei to the intralaminar thalamic nuclei were studied in cats with the use of light and electron microscopy. Almost all intralaminar nuclei were shown to obtain cerebello-thalamic projections. The entire complex of the central cerebellar nuclei serves as a source of such projections; yet, involvement of different nuclei is dissimilar. Destruction of the central and, especially, caudal regions of the fastigial nucleus evoked in the intralaminar thalamic nuclei degenerative changes in the nerve fibers (from swelling and development of varicosities up to total fragmentation). Pathological phenomena could be noticed in the most caudal regions of the above thalamic nuclear group, including the medial dorsal nucleus. Projections of the cerebellar interpositus nucleus were directed toward nearly the same regions of the intralaminar nuclei; degeneration was more intensive (covered thecentrum medianum) when posterior regions of the interpositus nucleus were destroyed. Destruction of the lateral cerebellar nucleus evoked a similar pattern of pathological changes, but degeneration was also observed in some structures of the ventral and anterior nuclear groups of the thalamus. Electron microscopic examination showed that degeneration of dark and light types developed in the fiber preterminals and terminals. It can be concluded that the central cerebellar nuclei project not only to the ventral complex of the thalamic nuclei, but also to the anterior, medial, and intralaminar nuclear groups (rostral and caudal portions).     

Brief communication: Proportions of the ventral half of the cerebellar dentate nucleus in humans and great apes

In a previous study about volume comparisons of the cerebellar complex in some hominoid species (1997), progressive development of only the lateral zone group of nuclei was found in the human cerebellar complex. This development was considered to be related not to bipedalism, but to versatile and coordinated finger movement, evolving after bipedalism was established. It was also considered a prerequisite for the evolution of human language. The lateral zone groups of nuclei are represented by the dentate nucleus. Therefore, the present study reports the development of the dentate nucleus in humans in comparison with that in some great apes. One finding is that the average value of ratios for nucleus size of the ventral half (v) to the dorsal half (d) (v/d) was found to be 2.11 in humans, while it was 1.64 in great apes. This finding shows that the greater part of progressive development of the dentate nucleus in humans is due to the development of its ventral half. Therefore, the fiber connection to the frontal association area from the cerebellar cortex, which is involved in the performance of higher cerebellar functions such as cognitive and language functions, would be mediated by the ventral half of the dentate nucleus.     

The morphology of the cerebellar nuclei of Galago and Tupaia

The cerebellar nuclei of the lesser bushbaby (Galago senegalensis) and the tree shrew (Tupaia glis) were studied. The cerebellar nuclear grey of Galago is divisible into a medial nucleus, a nucleus interpositus anterior, a nucleus interpositus posterior, and a lateral nucleus. The lateral nucleus is slightly concave medially suggestive of a primitive hilus. The interpositus nucleus is divided into anterior and posterior portions by a delicate lamina of fibers. The medial cerebellar nucleus is an irregular mass of cells located dorsal to the fourth ventricle. The cerebellar nuclear grey of Tupaia is also divisible into a medial nucleus, a nucleus interpositus anterior, a nucleus interpositus posterior, and a lateral cerebellar nucleus. The medial cerebellar nucleus is located dorsal to the fourth ventricle. The nucleus interpositus anterior and nucleus interpositus posterior are joined together and with the lateral nucleus in the caudo-ventral region. The NIA and NIP have an anterior-posterior relationship to each other and the lateral nucleus has no apparent undulations suggestive of early sacculations. The configuration of the cerebellar nuclei of Tupaia more closely resembles the more primitive patterns of the rat, hedgehog, and mole than those of Galago or other primates.     

Reorganization of the vestibular-thalamic projections following injury of the cerebellar interpositus and deiters vestibuar nuclei

Plastic reorganization of the vestibular-thalamic system was studied in adult cats. It was shown, that preliminary (3 months before) injury of the cerebellar contralateral nucleus interpositus or lateral vestibular nucleus of Deiters leads to reorganization of vestibular-thalamic projections. Ipsilateral projections to the ventrolateral nucleus of thalamus arised from vestibular nuclear complex since the pattern of normal representations to mentioned thalamic nucleus were changed. The peculiarities of distribution and morphological structure of vestibular neurons forming new projections to the ventrolateral thalamic nucleus were studied as well.     

Separate populations of neurons in the oculomotor nucleus project to the cerebellum and the abducent nucleus. A retrograde fluorescent double-labelling study in the cat

Retrograde transport of fluorescent substances was used in order to investigate possible branching of axons from neurons in the oculomotor nucleus in the cat. Rhodamine-B-isothiocyanate (RITC) was injected into the cerebellar hemisphere, while Fluoro-Gold was implanted into the abducent nucleus. Neurons single-labelled with either of the dyes were found in the oculomotor nucleus in all cases, but no double-labelled neurons were found. The labelled cells were smaller than motoneurons and located in partly overlapping areas along the dorsal border of the oculomotor nucleus, with the RITC labelled cerebellar projecting cells concentrated medially and the Fluoro-Gold labelled neurons projecting to the abducent nucleus concentrated laterally. The RITC labelled cells were found throughout the rostrocaudal extent of the nucleus, while the Fluoro-Gold labelled cells were mainly found caudally. The present findings demonstrate that oculomotor neurons projecting to the feline cerebellum and abducent nucleus represent separate cell populations.     

On the pars cerebellaris loci coerulei within the cerebellum of man

A flat cerebellar nucleus of melanin containing cells in the vicinity of the nucleus fastigii of man is described as part of the nucleus coeruleus.     

Cerebellar projections to the somatic pretectum in the cat

Neurons in the somatic pretectum receive input from the dorsal column nuclei (DCN) and project to a comparable "somatic" portion of the dorsal accessory nucleus of the inferior olive (DAO). This somatic DAO is reciprocally connected with the anterior interpositus nucleus of the cerebellum. One question that arises is whether this circuitry is further controlled by an output specifically from the anterior interpositus nucleus to the somatic pretectum. Wheatgerm agglutinin conjugated to horseradish peroxidase was injected into various parts of the cat pretectum. Injection sites were interpreted as including the somatic pretectum if neurons in the DCN were retrogradely labeled and if anterograde terminal labeling occurred in somatic DAO. The locations of retrogradely labeled neurons within the deep cerebellar nuclei were then compared in cases in which the injection sites included or excluded the somatic pretectum. In all cases in which the injection site included the somatic pretectum, retrogradely labeled neurons were observed in the anterior interpositus nucleus as well as in the lateral cerebellar nuclei. In some of these cases, neurons in the posterior interpositus and medial nuclei were also labeled. In contrast, in cases in which the pretectal injection site was located outside or at the border of the somatic pretectum, retrogradely labeled neurons were observed only in the lateral, posterior interpositus, and medial nuclei. Thus, the somatic pretectum appears to receive input primarily from neurons in the anterior interpositus nucleus, along with some input from neurons in the lateral nucleus. These results provide additional evidence for a pathway through the DCN in which sequentially processed somatic information has access to and is modulated by cerebellar circuitry. The existence of such a pathway supports the conclusion that neurons in the DCN convey somatic information important not only for cutaneous, kinesthestic, and other bodily sensations, but also for the control of movement.     

Rearrangement of parameters of efferent activity in generators of cyclic motor response produced by electrical stimulation of cerebellar inputs in cats

Rearrangement of the parameters of scratch and locomotor generators produced by electrical stimulation of the inferior olive and nucleus reticularis lateralis as well as the cerebellar fastigial nucleus and nucleus interpositus was investigated in decerebrate immobilized cats. Results showed that a comparable rearrangement of the time course of activity in both locomotor and scratch generators was produced by altering the nature of signals proceeding along mossy and climbing fibers alike. Maximum rearrangement of scratch and locomotor generator activity, as induced by electrical activation of the inferior olive and lateral reticular nucleus, is observed during the first half of flexor half-center operation in these generators. The scratch (unlike the locomotor) generator typically shows considerably rearranged efferent activity following electrical activation of nuclei of the cerebellum and cerebellar afferents. The article discusses mechanisms of cerebellar origin which may be responsible for exerting a corrective action on scratch and locomotor generators during change in the phase and amplitude parameters of cerebellar input signals.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vol. 24, No. 2, pp. 131–140, March–April, 1992.     

Comparative analysis of the neuronal organization of the corticocerebellar relay formations of the pons

Under nembutal narcosis on cats, intracellular electrophysiological studies have been made of common properties and differences in the neuronal organization of the nucleus reticularis tegmenti pontis and intrinsic pontine nuclei. Reciprocal connections of all the nuclei with the cerebellum and sensorimotor cortex were revealed. It was shown that the cerebellar peduncles are involved to a different extent in the transmission of cerebellofugal signals from the nucleus reticularis tegmenti pontis and the pontine nuclei; all these nuclei have different projections to the central cerebellar nuclei and receive different descending cortical impulsation. Functionally, the investigated cortico-cerebellar pontine relay structures supplement and duplicate each other.     

Correction of changes induced by toluene in the cortical and subcortical structures of albino rat brain

The number and weight of cells in the cortical and subcortical structures of the cerebral and cerebellar motor system in albino rats after a long-term exposure to toluene were determined. Toluene intoxication proved to kill projection neurons and interneurons in the sensorimotor cortex, ventrolateral thalamic nucleus, caudate nucleus, pallidum, red nucleus, and inferior olivary complex. The decreased number of cerebellar cells was mediated by atrophic changes as indicated by the decrease in the area and dry weight of Purkinje cells. The addition of plaferon LB to the diet attenuated the cytotoxic effect of toluene.     

Afferent connections of the dorsal magnocellularis area of the cat red nucleus

Location within the brain of retrogradely labeled neurons putting out projections from the dorsal magnocellularis area of the red nucleus was investigated by means of microiontophoretic injection of horseradish peroxidase into the dorsal magnocellularis area of the cat red nucleus. Projections were found from a number of hypothalamic nuclei, the centrum medianum, parafascicular and subthalamic nuclei, zone incerta, Forel's field, nucleus medialis habenulae, pontine and bulbar reticular formation, and the following midbrain structures: the central gray matter, superior colliculus, Cajal's interstitial nucleus, reticular formation, and the contralateral red nucleus. Projections were also identified proceeding from more caudally located structures: the cerebellar fastigial nucleus, facial nucleus, medial vestibular and dorsal lateral vestibular nuclei, and ventral horns of the spinal cord cervical segments. Connections between the substantia nigra and the red nucleus were clarified. Projections to the red nucleus from the cerebral cortex, interstitial and dentate (lateral) cerebellar nuclei, the nucleus gracilis and cuneate nucleus were found, confirming data presented in the literature. Bilateral trajectories of retrogradely labeled fiber systems are described.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 810–816, November–December, 1987.     

Organization of the sensory and motor nuclei of the glossopharyngeal and vagal nerves in lampreys

Anterograde and retrograde transport of horseradish peroxidase was used to examine the afferent and efferent projections of the glossopharyngeal and vagal nerves in the lamprey, Lampetra japonica. Except for the ganglion cells and motoneurons, the distribution patterns of HRP-positive elements differed little between the two nerves. Afferent fibers mainly terminated in the ipsilateral cerebellar area, medial octavolateralis nucleus, and between the ventral octavolateralis nucleus and descending tract and nucleus of the trigeminal nerve (dV). In the cerebellar area, most of the labeled fibers were located in the molecular zone, but some penetrated into the granular zone. In the rostral part of the medial octavolateralis nucleus, labeled fibers coursed from the middle to the lateral area, and in the caudal part, they were localized in the dorsal area of the nucleus. In the area between the dV and ventral octavolateralis nucleus, labeled fibers coursed near the dorsal margin of the rostral part of the dV, and in the caudal part, they shifted dorsally. Ganglion cells and motoneurons of each nerve were also labeled.     

Neurons in the rat lateral hypothalamic area integrate information from the gastric vagal nerves and the cerebellar interpositus nucleus

Previous investigations have demonstrated that the neuronal activity in the lateral hypothalamic area (LHA) is respectively modulated by afferent inputs from the gastric vagal nerves innervating the upper gastrointestinal tract, as well as the cerebellar interpositus nucleus (IN). The aim of this study was to examine whether the gastric vagal and cerebellar IN inputs converge onto single LHA neurons in rats, especially those sensitive to glycemia. Of the 114 LHA neurons recorded, 60 (52.6%) and 51 (44.7%) responded to gastric vagal and cerebellar IN stimulation, respectively. Of the 60 LHA neurons responsive to gastric vagal stimulation, 30 also responded to the cerebellar IN stimulus, indicating a convergence of gastric vagal and cerebellar inputs onto single hypothalamic cells. When the gastric vagal nerves and cerebellar IN were stimulated simultaneously, a summation of the responses was observed in all 6 neurons tested. Moreover, of 24 neurons that responded to both the gastric vagal and cerebellar IN stimuli, 15 (62.5%) were identified as glycemia-sensitive. These results demonstrate that the visceral information transmitted by the gastric vagal nerves and the somatic information forwarded by the cerebellar IN converge onto single LHA neurons, especially those sensitive to glycemia. The findings also suggest that integration of somatic-visceral responses related to short-term feeding regulation may take place in the LHA.     

Activation of cat pontine nuclei neurons produced by cortico- and cerebellofugal impulses

Extracellular recording techniques were used on cats anesthetized with Nembutal to illustrate antidromic activation of pontine neurons produced by stimulating the medial and occasionally the superior cerebellar peduncle, the cerebellar central nuclei, pyramidal tract, and sensorimotor region of the cortex. Of the pontine nucleus projection, that extending to the lateral cerebellar nucleus was the most clearly defined. Stimulation of the pyramidal tract, central cerebellar nuclei and the superior cerebellar peduncle was found to produce monosynaptic excitation of pontine neurons. The significance and special features of the connections identified are discussed in connection with cortico-pontocerebellar system function.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Amenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 38–48, January–February, 1988.     

Deleting the Arntl clock gene in the granular layer of the mouse cerebellum: impact on the molecular circadian clockwork

The suprachiasmatic nucleus houses the central circadian clock and is characterized by the timely regulated expression of clock genes. However, neurons of the cerebellar cortex also contain a circadian oscillator with circadian expression of clock genes being controlled by the suprachiasmatic nucleus. It has been suggested that the cerebellar circadian oscillator is involved in food anticipation, but direct molecular evidence of the role of the circadian oscillator of the cerebellar cortex is currently unavailable. To investigate the hypothesis that the circadian oscillator of the cerebellum is involved in circadian physiology and food anticipation, we therefore by use of Cre‐LoxP technology generated a conditional knockout mouse with the core clock gene Arntl deleted specifically in granule cells of the cerebellum, since expression of clock genes in the cerebellar cortex is mainly located in this cell type. We here report that deletion of Arntl heavily influences the molecular clock of the cerebellar cortex with significantly altered and arrhythmic expression of other central clock and clock‐controlled genes. On the other hand, daily expression of clock genes in the suprachiasmatic nucleus was unaffected. Telemetric registrations in different light regimes did not detect significant differences in circadian rhythms of running activity and body temperature between Arntl conditional knockout mice and controls. Furthermore, food anticipatory behavior did not differ between genotypes. These data suggest that Arntl is an essential part of the cerebellar oscillator; however, the oscillator of the granular layer of the cerebellar cortex does not control traditional circadian parameters or food anticipation.     

Effect of injury to the lateral reticular nucleus and nuclei of the inferior olive on electrical responses of the cerebellar cortex evoked by vagus nerve stimulation in cats

The role of the lateral reticular nucleus and nuclei of the inferior olive in the formation of cerebellar cortical evoked potentials in response to vagus nerve stimulation was determined in experiments on 28 cats anesthetized with chloralose and pentobarbital. After electrolytic destruction of the lateral reticular nucleus, in response to vagus nerve stimulation, especially ipsilateral, lengthening of the latent period and a decrease in amplitude of evoked potentials were observed; after bilateral destruction of this nucleus, evoked potentials could be completely suppressed. It is concluded that the lateral reticular nucleus relays interoceptive impulses in the vagus nerve system on to the cerebellar cortex. Additional evidence was given by the appearance of spike responses of Purkinje cells, in the form of mainly simple discharges, to stimulation of the vagus nerve. After destruction of the nuclei of the inferior olive, the latent period and the number of components of evoked potentials in response to vagus nerve stimulation remained unchanged but their amplitude was reduced. The role of the nuclei of the inferior olive as a regulator of the intensity of the flow of interoceptive impulses to the cerebellum is discussed.N. I. Pirogov Medical Institute, Vinnitsa. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 290–299, May–June, 1977.     

Synaptic processes produced in cat rubrospinal neurons by stimulating the cerebellar nucleus interprositus

The activity produced in red nucleus rubrospinal neurons by stimulating the cerebellar nucleus interpositus was investigated in cats anesthetized with nembutal. Analysis of field potentials together with summated and single EPSP following paired and frequency stimulation of this structure revealed facilitation at cerebello-rubral synapses. It was found that this facilitation was not mediated by changes in presynaptic volleys. It is suggested that modification of the effectiveness of transmission is determined by characteristic features of the operation of cerebellar synapses on red nucleus neurons.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 630–636, September–October, 1987.     

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

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

Spatial organization of inhibitory control of activity of vestibulospinal Deiters' neurons by Purkinje cells in the anterior lobe of the cerebellum

The topographical distribution of vestibulospinal neurons in Deiters' nucleus was investigated by a microelectrode method. By contrast with observations made in morphological experiments, the localization of antidromically identified vestibulocervical (C-neurons) and vestibulolumbar (L-neurons) cells was found not to be limited to the ventral middle and rostral third of the nucleus (the forelimb region) and caudodorsal part of the nucleus (hind limb region), but to include the whole of the ventral and dorsal half of the nucleus, respectively. The zones of localization of these two groups of neurons are not confined to a single layer: C-neurons are found in the dorsal half of the nucleus and L-neurons in its ventrocaudal part also. Analysis of the distribution of monosynaptic IPSPs arising in response to activation of Purkinje cells in the vestibulospinal neurons showed that C-neurons are controlled chiefly from the forelimb zone of the cerebellar cortex whereas L-neurons are controlled equally by inhibitory influences from the forelimb and hind limb zones of the anterior lobe of the cerebellar cortex.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 11, No. 1, pp. 54–64, January–February, 1979.