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PubMed1998

Lugaro cells target basket and stellate cells in the cerebellar cortex.

Lugaro cells are fusiform neurons located just beneath the Purkinje cell layer. Their axon projects profusely in the molecular layer and emits some collaterals in the granular layer. We have analysed the molecular layer postsynaptic targets of a Golgi-impregnated Lugaro cell, using the electronmicroscopic gold-toning procedure and post-embedding anti-GABA immunocytochemistry. All the gold-labeled neuritic and somatic profiles were GABA-positive, thus confirming that the Lugaro cell is an inhibitory interneuron. The axonal varicosities of this cell form multiple symmetrical synaptic junctions with basket and stellate cell somata and proximal dendrites, and, perhaps, with the molecular layer dendrites of Golgi interneurons. Lugaro cells thus seem to exert a feed-back inhibitory control on Purkinje cells.

Animals↗

PubMed1982

The effects of chlorpromazine and phenobarbital on vasculogenesis in the cerebellar cortex.

The morphological effects of two chemically different neuroactive drugs (chlorpromazine and phenobarbital) on vasculogenesis in rat cerebellum were examined to determine the presence of vascular alterations. Therapeutic dosages of both drugs were chronically administered to separate groups of maternal rats beginning on days 10, 13, 15, 18, and 21. In chlorpromazine-treated animals the specific length of blood vessels was most severely reduced in the Purkinje cell layer. Animals treated with phenobarbital demonstrated an initial reduction in specific length in the Purkinje cell layer but returned to control values by day 21 postnatal (p.n.). Blood vessels in the molecular and granular layers showed little change. The observed changes have been discussed in relation to possible mechanisms and their relationship to neurogenesis.

Animals↗

PubMed2004

Displaced granule cells in the molecular layer of the cerebellar cortex in mice treated with methylazoxymethanol.

To study the effect of a reduced granule cell number on the development of the cerebellum, mice were administered with methylazoxymethanol (MAM) at birth and examined histologically at 21 days of age. In these mice, green fluorescent protein had been knocked in within the glutamic acid decarboxylase 67 gene, resulting in fluorescent GABAergic neurons. In severe cases, granule cells were greatly reduced in number and mixed with Purkinje cells instead of forming layers. In about 10% of the MAM-treated mice, an ectopic cell layer consisting of granule cells was observed within the molecular layer. Concomitantly, basket cells disappeared. The transient interruption of granule cell production in the external granular layer presumably resulted in their incomplete migration through the molecular layer.

Animals↗

PubMed1980

[Glioarchitectonics of the cerebellar cortex and medulla of cows during postnatal development].

For the studies 2 cerebella of newborn calves and 4 cerebella of 4-week-old calves, and 1-, 3-, 6-, 10- and 14-year-old cows were used at a time. Paraffin cerebellum sections cut with a microtome were stained with hematoxylin and eosin and after Klüver Barrer's method as well as impregnated after the method of Klatzo, Ramon Moliner and Robain. In the material studied, glioarchitectonics of the cortex and medullary substance of the cerebellum was described. Morphological features of astrocytes, oligodendrocytes (light, medium stained, and dark) and microglia cells (round and pericytes) were described in the glia occurring in these parts of the cerebellum. In the particle layer and in that of purkinje cells morphological features of Fananas and Bergman cells, representing a variety of astrocytes, were described. Because of a great similarity of glia cells to granular, basket and stellate cells of the cerebellum, morphological features of these neurons were also described, giving a particulate attention to the differences in the structure of the latter and glia cells.

Aging↗

PubMed2002

Pontine and lateral reticular projections to the c1 zone in lobulus simplex and paramedian lobule of the rat cerebellar cortex.

Spatial localization and axonal branching in mossy fiber projections to two rostrocaudally-separated regions of the 'forelimb' c1 zone in lobulus simplex and paramedian lobule were studied in rats using a retrograde double-labelling tracer technique. In four animals the two cortical regions were localized electrophysiologically and each was micro-injected with tracer material, yielding a total of eight different cases. Single- and double-labelled cell bodies were plotted in the basal pontine nucleus (BPN), nucleus reticularis tegmenti pontis (NRTP), and the lateral reticular nucleus (LRN). As a control, cells labelled in the contralateral inferior olive were also counted. The parts of the c1 zone in lobulus simplex and the paramedian lobule were found to receive mossy fiber inputs from similar regions of BPN, NRTP and LRN. Double-labelled cells were not found in NRTP but were present in BPN and LRN (on average 6% and 25% of the smaller single-labelled population, respectively). The incidence of double-labelled cells in the olive and LRN was positively correlated, but no relation was found between olive and BPN, suggesting a zonal organization within the mossy fiber projections from LRN, but not from the pons. In quantitative terms, the c1 zone in lobulus simplex received a greater density of mossy fiber projections from BPN, NRTP and LRN than the c1 zone in the paramedian lobule. This suggests that the two parts of the same cerebellar cortical zone differ, at least partially, in regard to their inputs from three major sources of mossy fibers. This is consistent with the modular hypothesis and could enable a higher degree of parallel processing and integration of information within different parts of the same zone.

Animals↗

PubMedDate not supplied

Menkes disease: a Golgi and electron microscopic study of the cerebellar cortex.

A neuropathological study of a case of Menkes disease is reported, illustrating the involvement of different types of neuronal cells. The cerebellum showed the most striking abnormalities: severe lack of internal granule cells. Purkinje cells with weeping willow pattern, numerous segmental enlargements of dendritic trunks and secondary branches, and presence of numerous eosinphilic spherical bodies in the molecular layer were the most conspicuous features. Using electron microscopy, the dendritic enlargements were observed to be made of both proliferated and enlarged mitochondria, and of saccules of smooth endoplasmic reticulum. The spheroid bodies in the molecular layer were mainly made of concentric lamellar structures which seemed to be proliferated smooth endoplasmic reticulum. The relationship between these morphological abnormalities and the metabolic disorder of Menkes disease is discussed.

Brain Diseases, Metabolic↗

PubMed1986

Anatomical evidence for enkephalin immunoreactive climbing fibres in the cerebellar cortex of the opossum.

Enkephalin immunoreactivity is present in the cerebellum of the adult opossum within axonal arbors that resemble mature climbing fibres. In the developing cerebellum, enkephalinergic axons form pericellular nests around the perikarya of Purkinje cells in a manner which resembles developing climbing fibres seen in Golgi impregnations. Serial electron micrographs of adult climbing fibres reveal elongate enkephalin immunoreactive profiles that contain synaptic vesicles and make contact with the thorns and shafts of Purkinje cell dendrites. These results suggest that a peptide, enkephalin or an enkephalin-like substance may mediate synaptic interactions between certain populations of climbing fibres and Purkinje cells in the cerebellum of the opossum. Enkephalin immunoreactive axonal arbors, present in the molecular layer, are localized in restricted areas of vermal lobules II-VIII and X. The intermediate cortex and hemispheres are devoid of enkephalinergic climbing fibres except in restricted areas of the paramedian lobule, paraflocculus and the flocculus. In an attempt to establish the origin of enkephalin axons in the cerebellum, a double labelling technique that combines retrograde labelling of cells with horseradish peroxidase and enkephalin immunohistochemistry has been employed. Enkephalin immunoreactive neurons within specific portions of the medial accessory olive are retrogradely labelled in this paradigm. The presence of enkephalin immunoreactivity in selected climbing fibres provides evidence for chemical heterogeneity within one of the major afferent systems to the cerebellum previously thought to be uniform in its transmitter content.

Animals↗

PubMed2002

Learning-induced multiple synapse formation in rat cerebellar cortex.

Strengthening of synaptic connections has been proposed to underlie information storage in the brain, and experience-dependent increases in synapse number have been observed. However, the effect of these new synapses on the specific connectivity, and thus function, of a given brain area remains largely unknown. We report here that motor learning specifically induces the formation of multiple synapses--two post-synaptic contacts at a single pre-synaptic varicosity--in the cerebellum. Rats undergoing motor learning had more multiple synapses (two Purkinje cell spines contacting a given parallel fiber varicosity) per Purkinje cell than did active or inactive controls. The formation of multiple synapses provides an additional connection between a given parallel fiber and Purkinje cell, thereby enhancing particular pathways, and may constitute a fundamental mechanism of neural encoding.

Animals↗

PubMed1991

Nuclear and axonal localization of Ca2+/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex.

The granule cell-enriched Ca2+/calmodulin-dependent protein kinase (CaM kinase-Gr) is a recently discovered neuron-specific enzyme. The kinase avidly phosphorylates synapsin I and contains a polyglutamate sequence, which suggests an association with chromatin as well. A possible role in synapsin I phosphorylation and in nuclear Ca2+ signaling was supported by immunochemical and ultrastructural examination of CaM kinase-Gr distribution. CaM kinase-Gr immunoreactivity was present in the molecular and granule cell layers of the rat cerebellum. This pattern corresponded to the occurrence of the enzyme in the granule cell axons and nuclei, respectively. Immunoblots confirmed these findings. Thus, CaM kinase-Gr may mediate and coordinate Ca2(+)-signaling within different subcellular compartments.

Animals↗

PubMed1983

Somatotopy of climbing fiber branching to the cerebellar cortex in cat.

The study was aimed at determining the distribution and incidence of the inferior olive axonal branching as related to the somatotopic organization of the climbing fiber system in cat. Multiple fluorescent tracing was used. In a first set of experiments, spectrally different fluorescent tracers were injected into somatotopically defined areas of the anterior lobe-pars intermedia and of the paramedian lobule. Retrogradely labeled cells were found to be localized in well-segregated face-forelimb or hindlimb olivary domains, within the various subdivisions. A large and consistent number of the olive cells were found to send axonal branches to face-forelimb or hindlimb regions of the anterior lobe-pars intermedia and of the paramedian lobule. It was also found that inferior olive branching is restricted to somatotopically corresponding areas of the two lobes. In a second set of experiments the same technique was used to check whether the inferior olive neurons which project to the forelimb areas of the anterior lobe-pars intermedia and the paramedian lobule also send collaterals to the face-forelimb areas of crus II (medial crus II). The data show that different sets of neurons projecting either to the face-forelimb areas of crus II and anterior lobe-pars intermedia or of crus II and paramedian lobule coexist within the face-forelimb related olivary domains with the set of neurons projecting to the face-forelimb areas of the anterior lobe-pars intermedia and paramedian lobule. Neurons branching to the 3 cerebellar regions were observed only occasionally. Therefore, at least for the face-forelimb-related cerebellar areas, the climbing fiber branching can be said to originate in sets of inferior olive neurons that connect different pairs of somatotopically homologous cerebellar cortical areas. The branching pattern is present in all the cortical zones studied, namely C1-C3, C2, D1 and D2, and appears to be a general feature of the olivocerebellar system.

Afferent Pathways↗

PubMed1980

Neonatal neuronal necrosis: its relationship to the distribution and maturation of oxidative enzymes of newborn cerebral and cerebellar cortex.

Seventeen brains showing neuronal necrosis after severe perinatal 'asphyxia' were re-examined. In particular the distribution of lesions, which generally involved all layers of the cerebral cortex and was only occasionally laminar, was contrasted with the laminar pattern of maturation of oxidative enzymes in comparable regions of normal newborn brains. In the cerebellum, where necrosis of neurones of the vermis was prominent compared with relative sparing of neurones of the lateral hemispheres, a closer correlation with the pattern of maturation of oxidative enzymes was noted. The rarity of laminar necrosis in the cerebral hemispheres suggests that factors other than pure hypoxic-hypoxia are important in most cases in determining the distribution of lesions, whereas in the cerebellum the earlier maturation of neurones and hypoxic-hypoxia per se are important in determining the localization of lesions.

Asphyxia Neonatorum↗

PubMed1981

[Morphometric study of the Purkinje cells of the canine cerebellar cortex].

A differential morphometric analysis of the Purkinje cell (PC) population in 3 functional zones of the cerebellum was performed in 7 intact mongrel dogs of both sexes. The number of normal (light, dark, intermediate) and morphologically changed neurons was counted per 1 mm of the PC layer. It was shown that the medial, intermedial and lateral zones of the cerebellum did not differ in the number of dark and intermediate PC. The number of light PC in the medial zone was significantly less than in the intermedial and lateral ones. Consequently the difference also arose in the total PC number. It was discovered that PC distribution was not uniform either in the superior or inferior parts of cerebellum gyri. The morphological differences in the composition of the PC population of the medial, intermedial and lateral zones of the cerebellum are likely to reflect the functional inconsistency of these zones.

Animals↗

PubMed1990

Morphological changes of astroglia in the cerebellar cortex of developing mice after neonatal administration of cytosine arabinoside.

Neonatal administration of cytosine arabinoside (Ara-C) induced marked hypoplasia of the mouse cerebellum. In 17-20-day-old mice with neonatal Ara-C injections, the external granular layer was still preserved as an irregular cell laminae in the superficial part of the cerebellum, in contrast to its complete disappearance in normal animals at these stages. Immunohistochemical examination using anti-glial fibrillary acidic protein and monoclonal antibody-1D11 (Ono et al: Dev. Brain Res., 50:154-159, 1989) demonstrated malformation of a palisade-like arrangement of labeled glial fibers in the superficial part of the Ara-C treated mouse cerebellum. Furthermore, the immunoreactive astroglia were observed just beneath the pial membrane and their processes were oriented to the deeper part of the molecular layer.

Animals↗

PubMed1992

Differential subcellular distribution of the alpha 6 subunit versus the alpha 1 and beta 2/3 subunits of the GABAA/benzodiazepine receptor complex in granule cells of the cerebellar cortex.

The distribution of the alpha 6 subunit of the GABAA receptor has been established in rat cerebellum and compared to the distribution of the alpha 1 (cat) and the beta 2/3 (rat, cat) subunits, using immunocytochemistry. The synapses established by Golgi cell terminals on the dendrites of granule cells were immunoreactive for the alpha 6, alpha 1 and beta 2/3 subunits in virtually all glomeruli, indicating that two variants (alpha 1 and alpha 6) of the same subunit are co-localized at the same synapses. The somatic membranes of the granule cells, which receive no synapses, were immunopositive for the alpha 1 and beta 2/3 subunits, but not for the alpha 6 subunit. Thus, the alpha 1 and the beta 2/3 subunits are located at both synaptic and extrasynaptic sites, but the alpha 6 subunit is detectable only at synaptic sites.

Animals↗

PubMed1996

High expression of Bcl-x protein in the developing human cerebellar cortex.

The gene bcl-x, which is related to a bcl-2, regulates programmed cell death. bcl-x may function in the development of the nervous system. We raised a polyclonal antibody against human Bcl-x protein, and investigated its distribution in the developing human cerebellum. Western blotting revealed that Bcl-x expression in the cerebellum is higher in the fetal, than in the postnatal period. Immunohistochemical studies of fetal brains localized intense Bcl-x immunoreactivity in the granule cell processes at 13-22 gestational weeks and in the Purkinje cell bodies at 24-38 weeks. The immunoreactivity decreased after birth, but was retained in the Purkinje cells at a low level until adulthood. These results suggested that Bcl-x expression in the cerebellum is developmentally regulated and involved specifically in the development of neuronal subpopulations.

Adult↗

PubMed1988

Development of parasagittal zonation in the rat cerebellar cortex: MabQ113 antigenic bands are created postnatally by the suppression of antigen expression in a subset of Purkinje cells.

Monoclonal antibody mabQ113 recognizes a polypeptide antigen that, in the adult cerebellum, is confined to a subset of Purkinje cells that are clustered together to form parasagittal bands interposed by similar nonimmunoreactive bands. The Purkinje cell compartments are congruent with bands of climbing fibers projecting from subregions of the inferior olivary complex (IOC). The array of mabQ113 parasagittal bands appears late in the development of the cortex. Weak mabQ113 immunoreactivity is first seen at postnatal day 6 (P6) in the Purkinje cells of the posterior lobe of the vermis. From the earliest stages there are signs of differential expression of the mabQ113 antigen in clusters of Purkinje cells: four mabQ113+ clusters are clearly present in the posterior lobe of the vermis at P6-P7. Their relation to the adult band display remains uncertain. During the next few days immunoreactivity spreads rostrally throughout the rest of the vermis and laterally to include the Purkinje cells in the hemispheres, until by P12 all the Purkinje cells in the cerebellum are mabQ113+. Nevertheless, signs of the adult band display are seen already in the vermis where the cells destined to become the vermal mabQ113+ bands (P1+, P2+ and P3+) stain more intensely than their neighbours. Following the stage of global mab113 epitope expression, bands are created by the selective suppression of immunoreactivity by Purkinje cells in the P- regions. By P15 the mabQ113+ and mabQ113- bands are clearly differentiated in the vermis and selective staining has begun to appear in the hemispheres also. The band pattern matures gradually during the third and fourth postnatal weeks until the adult appearance is attained by P30. The cerebellar afferent projections were lesioned to explore the interplay of cerebellar input and mabQ113 expression. The olivocerebellar projection was lesioned bilaterally by using 3-acetylpyridine in the adult and unilaterally in the newborn by electrolytic lesion and unilateral inferior cerebellar pedunculectomy. Mossy fibers from the dorsal and ventral spinocerebellar tracts were lesioned surgically both in adults and in newborn and trigeminal projections to the cerebellum were removed in the newborn by unilateral ablation of the spinal trigeminal nucleus. The consequences of total blockage of vibrissal and hindlimb inputs were also explored in both adults and neonates. None of these treatments led to a modification in the pattern of mabQ113 epitope expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1980

Guanosine triphosphate: an endogenous compound in the rabbit cerebellar cortex which couples the beta-adrenergic receptor to adenylate cyclase.

The guanyl nucleotides GTP and GDP are endogenous factors in the rabbit cerebellum which contribute to the in vitro coupling of the beta-adrenergic receptor to adenylate cyclase. Repeated washing of the particulate material removes these endoactivity to beta-adrenergic agonists. The endogenous GTP and GDP, isolated by high pressure liquid chromatography, mimic the ability of the supernatant both to restore the coupling of receptor and enzyme and to increase basal enzyme activity. The effectiveness of GDP reflects its conversion to GTP during the assay. GTP does not affect either the number of [3H]dihydroalprenolol binding sites or the affinity of these sites for L-isoproterenol; furthermore, GTP does not cause a shift in activation affinity of enzyme activity for isoproterenol. Thus, the guanyl nucleotides are endogenous constituents of the mammalian brain which are essential for the functional 'coupling' of beta-adrenergic receptors to adenylate cyclase.

Adenylyl Cyclases↗

PubMed1981

Developmental changes of synapses in the cerebellar cortex of the rat. A quantitative analysis.

Synaptogenesis in the molecular layer of the vermis cortex in Wistar rats between 1 and 25 days after birth was investigated. After staining with OSO4, the following parameters were measured: the density of synaptic profiles; the percentage of the neuropil area occupied by synapses; the mean diameter of the boutons; and the numerical density of synapses in a defined volume. The detailed topographical analysis enabled us to show the following: the first synapses appear diffusely in the molecular layer; after the 10th day a synaptic gradient is present between the depth and the surface area (this gradient can be found by the count of the synapses and by studying the spatial distribution of the synaptic area); this gradient is no longer seen at the 25th day, when the density of synapses is relatively uniform throughout the whole molecular layer.

Aging↗