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PubMed1999

Remote regional cerebral blood flow consequences of focused infarcts of the medulla, pons and cerebellum.

UNLABELLED: The aim of this study was to evaluate regional and remote diaschisis of inferior brain stem or cerebellar infarcts in 25 patients presenting with relatively limited lesions. Patients presented with medullary, pontine or cerebellar infarction. METHODS: Lesions were evaluated on MRI (0.5 T). Regional cerebral blood flow (rCBF) was assessed by means of SPECT, after injection of 9rmTc-hexamethyl propyleneamine oxime (HMPAO) and, when possible, inhalation of 133Xe in the same session. For each method, asymmetry indices (Als), comparing contralateral to ipsilateral rCBF values, were calculated in four areas of each cerebral hemisphere and in the cerebellum and later compared with values obtained in healthy subjects (P = 0.05). RESULTS: Higher rCBF values were observed in the contralateral cerebellum in 2 of 7 patients with selective lateral medullary lesions, and cerebellar Als were significantly increased. When a cerebellar infarct was associated with a lateral medullary lesion, the cerebellar and contralateral hemispheric asymmetries were more severe. Unilateral paramedian pontine infarcts had more frequent consequences on the cerebellum (2 of 3 cases), with rCBF or tracer uptake being reduced in the ipsilateral or the contralateral lobe. Inverse cerebral hemispheric asymmetry could then be observed. Bilateral pontine lesions were difficult to evaluate. Using 99mTc-HMPAO, discrete cerebellar asymmetry was observed in 3 of 6 cases. Pure cerebellar infarcts in the posterior inferior cerebellar artery territory were always associated with a severe ipsilateral flow drop in the cerebellum, and contralateral hemispheric diaschisis was frequent (3 of 4 patients), predominating in the frontotemporal cortex and subcortical structures. This was also more obvious using 99mTC-HMPAO than 133Xe. Variance analysis showed that hemispheric diaschisis was more severe in mixed brain stem and cerebellar infarcts than in pure cerebellar or brain stem lesions. Furthermore, cerebellar and hemispheric AI values were not correlated with measurements of clinical deficits, disability or handicap. CONCLUSION: Unilateral and limited inferior brain stem lesions can have ipsi- or contralateral consequences on the cerebellum and cerebral hemispheres rCBF. These remote effects are related to lesions of the main pathways joining these structures, resulting in deactivation and, in some cases, overactivation. Contrary to what has been suggested, consequences on cerebral hemispheres are more severe in mixed cerebellar and brain stem infarcts than in pure cerebellar lesions.

Adult↗
PubMed2002

Artificial gravity and functional plasticity of nerve system. L-[14C]-glutamate uptake by nerve terminals from rat cerebellum and cerebral hemispheres under hypergravity stress.

We have investigated the effects of altered gravity on the kinetic parameters of glutamate transport activity. We observed no differences in Km values for cerebellum and cerebral hemisphere nerve terminals (synaptosomes) between control rats- 18,2 +/- 7,6 micromoles (cerebellum), 10,7 +/- 2,5 micromoles (cerebral hemispheres) and animals exposed to hypergravity- 23,3 +/- 6,9 micromoles (cerebellum), 6,7 +/- 1,5 micromoles (cerebral hemispheres). The similarity of this parameter for the two studied groups of animals showed that affinity of glutamate transporter to substrate in cerebellum and cerebral hemispheres was not sensitive to hypergravity stress. The maximal velocity of L-[14C]-glutamate uptake (Vmax) reduced for cerebellum synaptosomes from 9,6 +/- 3,9 nmol/min/mg of protein in control group to 7,4 +/- 2,0 nmol/min/mg of protein in animals, exposed to hypergravity stress. For cerebral hemisphere synaptosomes the maximal velocity significantly decreased from 12,5 +/- 3,2 nmol/min/mg of protein to 5,6 +/- 0,9 nmol/min/mg of protein, respectively.

Journal Article↗
PubMed1997

Distribution of tyrosine hydroxylase-immunoreactive afferents to the cerebellum differs between species.

The indirect antibody peroxidase-antiperoxidase technique was used to determine the laminar and lobular distribution of catecholaminergic afferents in the adult mouse, opossum, and cat cerebellum. A monoclonal antibody to tyrosine hydroxylase (TH) revealed a plexus of thin varicose fibers that exhibited a different density and distribution pattern for each species. In the cat, TH-immunoreactive fibers were sparsely distributed to all laminae, lobules, and nuclei of the cat cerebellum except for an area of elevated density in the ventral folia of lobules V and VI. In the opossum, TH-positive fibers were uniformly and densely distributed in the granule and Purkinje cell layers; they were more abundant in vermal lobules V-VI than in more anterior and posterior lobules, particularly I and X. Numerous TH-immunoreactive fibers were found in all four cerebellar nuclei of the opossum. In the mouse, TH-positive fibers formed a dense plexus within all cerebellar lobules, laminae, and nuclei. The mouse also exhibited numerous TH-immunoreactive Purkinje cells that were localized predominantly within vermal lobules VI-X, the paraflocculus, and flocculus. In addition to the interspecies differences in the distribution of catecholaminergic fibers within the cerebellum, comparison of this plexus to that previously described for serotonin in these species reveals that the relative densities and distribution patterns of catecholaminergic and serotoninergic fibers also vary between species. It is thus hypothesized that in each species a given monoamine has a unique net effect on cerebellar output that is determined by its effects on different neuronal populations within the cerebellum.

Afferent Pathways↗
PubMed1998

NMDA receptor-dependent nitric oxide and cGMP synthesis in brain hemispheres and cerebellum during reperfusion after transient forebrain ischemia in gerbils: effect of 7-Nitroindazole.

In this study, the N-Methyl-D-Aspartate (NMDA) receptor-dependent nitric oxide and cyclic GMP (cGMP) synthesis in the course of reperfusion after 5 min of ischemia in gerbil brain hemispheres and cerebellum were investigated. Moreover, the role of the neuronal isoform of nitric oxide (NO) synthase (nNOS) in liberation of NO in postischemic brain and the involvement of NO in membrane lipoperoxidations activated during reperfusion were evaluated. Enhancement of Ca2+/calmodulin-regulated NOS activity and cGMP level in brain hemispheres and in cerebellum during reperfusion was found to be coupled to the activation of the NMDA receptor. cGMP concentration 40% above the control level was observed to persist up to 7 days after ischemia. The amount of conjugated double bounds in membrane lipids and the level of thiobarbituric acid reactive substances were increased exclusively in brain hemispheres, indicating activation of lipid peroxidation. The NMDA receptor antagonist, MK-801, eliminated, and a rather selective nNOS inhibitor, 7-Nitroindazole (7-NI) attenuated, NMDA receptor-evoked enhancement of NOS activity and cGMP level in brain hemispheres and in cerebellum during reperfusion. Moreover, 7-NI decreased significantly membrane lipid peroxidation during the early time of reperfusion. Histological examination demonstrated that 7-NI protects against death a selected population of neuronal cells in CA1 layer of hippocampus. It is suggested that NMDA receptor dependence of NO release during reperfusion is responsible for the degeneration of some populations of neurons and that the effect is mediated by activation of free radical formation and lipid peroxidation. Moreover, in cerebellum, ischemia-evoked activation of glutamatergic system stimulates NO-dependent signal transmission. Our results indicated that 7-NI has a significant ameliorating effect on biochemical alterations evoked by ischemia, suggesting nNOS inhibitors as a potential therapeutic agents in reperfusion injury.

Animals↗
PubMed2000

Involvement of GIRK2 in postnatal development of the weaver cerebellum.

We demonstrate that the homozygous weaver granule neurons cultured on a laminin substratum fail to express inwardly rectifying potassium currents, including a functional G-protein coupled inwardly rectifying potassium (GIRK)2 potassium channel. By contrast, both normal and weaver Purkinje cells express inwardly rectifying potassium currents, and normal granule cells exhibit inwardly rectifying potassium currents inducible with GTP-gamma-S. In protein extracts of the vermal postnatal day (P)5-9 weaver cerebellum, the GIRK2 protein could not be detected by Western analysis, although the GIRK2 protein was detectable in extracts of the normal vermis. Northern analysis indicated that during early postnatal cerebellar development, the GIRK2 mRNA is expressed at extremely low levels being detectable at P18-23 in the normal but not yet in the homozygous weaver cerebellum. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the GIRK2 mRNA was detected in both normal and weaver cerebella, but quantitative PCR confirmed that the weaver cerebellum expressed the GIRK2 gene at significantly lower levels as compared to the normal cerebellum (P = 0.01, paired t-test). Sequencing indicated that the weaver GIRK2 channel gene had the point mutation proposed to be responsible for the weaver phenotype. Rescue of both survival and neurite outgrowth of the cultured vermal weaver granule neurons by verapamil (Liesi and Wright, 1996; Liesi et al., 1999) induced expression of immunocytochemically detectable levels of the GIRK2 protein. Sequencing revealed that the GIRK2 mRNA of the rescued weaver granule neurons remained the mutated variant of the GIRK2 channel gene. Our results indicate that expression of the mutated GIRK2 protein and/or mRNA in the weaver granule neurons may be an indicator of rescue rather than death of the weaver granule neurons. That the weaver granule neurons expressed no functional GIRK2 receptors during a time period of neuronal death and migration failure suggests that the point mutation in the H5 membrane spanning region of the GIRK2 gene may associate with, but not be responsible for the weaver phenotype.

Animals↗
PubMed2000

Expression of the AMF/neuroleukin receptor in developing and adult brain cerebellum.

The peptide sequence of autocrine motility factor (AMF), a tumor secreted cytokine that induces cell motility, corresponds to that of the previously identified cytokine/enzyme, neuroleukin/glucose-6-phosphate isomerase. Neuroleukin is a neurotrophic factor that promotes neuronal survival and sprouting at the neuromuscular junction. The AMF receptor (AMF-R) has been identified and shown to be highly expressed in malignant tumors with minimal expression in adjacent normal tissue. Neuroleukin mRNA is highly expressed in the cerebellum and we therefore undertook a developmental study of AMF-R expression in rat cerebellum. As determined by immunoblot, AMF-R is expressed at equivalent high levels in brain and cerebellum of postnatal day 5 (P5) and 12 (P12) rats and at significantly reduced levels in the adult. Coimmunofluorescence studies with MAP-2 and gamma-actin revealed that at P12, AMF-R was mainly localized to Purkinje and granule cells. Moreover, the premigratory cells of the external granular layer were also immunoreactive for AMF-R suggesting a role for AMF-R in granule cell migration during cerebellar development in the first two weeks after birth. In the adult, AMF-R distribution was similar to P12, although weaker, and was localized to Purkinje and granule cells. AMF-R labeling of GFAP positive glial processes could not be detected in cerebellar sections although in cerebellar primary cultures, both neurons and glial cells were labeled for AMF-R. In neurons, AMF-R labeling was present in the cell body, neurites and growth cones. These data indicate that regulation of the neurotrophic function of neuroleukin might be regulated spatially and temporally by expression of its receptor, AMF-R, in developing and adult cerebellum.

Actins↗
PubMed1999

Role of caspases in ionizing radiation-induced apoptosis in the developing cerebellum.

Caspase activation and dependence on caspases has been observed in different paradigms of apoptotic cell death in vivo and in vitro. The present study examines the role of caspases in ionizing radiation-induced apoptosis in the developing cerebellum of rats subjected to a single dose (2-Gy gamma rays) of whole-body irradiation at postnatal day 3. Radiation-induced apoptosis in the external granule cell layer, as defined by the presence of cells by extremely condensed, often fragmented nucleus, which were stained with the method of in situ end-labeling of nuclear DNA fragmentation, first appeared at 3 h and peaked at 6 h following irradiation. Increased expression of the precursors of caspase 1 (ICE), 2 (Nedd2), 3 (CPP32), 6 (Mch2), and 8 (Mch5 and FLICE), and increased expression of active caspase 3, as revealed by immunohistochemistry, were observed in the external granule cell layer of the cerebellum. Radiation-induced apoptosis was accompanied by an increase in the expression of the poly(ADP-ribose) polymerase (PARP) fragment of about 89 kD, as revealed by Western blots of cerebellar homogenates. This was not associated with modifications of protein kinase Cdelta and Lamin B. Concomitant injection in the culmen of the cerebellum in irradiated rats of high doses of Y-VAD-cmk, DEV-fmk, or IETD-fmk resulted in decreased expression of the PARP fragment in cerebellar homogenates. This was accompanied by a decrease in the expression of active caspase 3, as shown by immunohistochemistry. These observations suggest caspase activation following ionizing radiation. However, no differences in the number and morphological and biochemical characteristics of apoptotic cells, including strong nuclear and cytoplasmic c-Jun/AP-1 (N) expression, were observed between irradiated and both irradiated and caspase inhibitor-treated rats. Taken together, these observations suggest that the caspases examined are not essential for radiation-induced apoptosis in the developing cerebellum.

Animals↗
PubMed1999

De novo expression of lipocortin-1 in reactive microglia and astrocytes in kainic acid lesioned rat cerebellum.

An understanding of the role of reactive glia in the neurodegenerative/regenerative process requires a knowledge of the molecules synthesised by these cells following trauma. We investigated the cellular localisation of lipocortin-1 (LC-1), a putative neuroprotective agent, in cryostat sections of normal and kainic acid lesioned rat cerebellum. In the normal cerebellum lipocortin-1 immunoreactivity was detected in Purkinje cell bodies and molecular layer interneurons. Following kainic acid (1 microg) induced lesions, it was rapidly upregulated in activated microglia, from which it appeared to be secreted. At later time points it was detected in activated astrocytes. LC-1 protein levels were quantified by a sensitive and specific ELISA. Compared to control cerebellum, LC-1 levels were dramatically elevated following lesion, peaking at 3 days: 760% of basal (unlesioned) levels. In situ hybridisation studies revealed a marked upregulation of LC-1 mRNA at 1 and 3 days following the lesion, indicating the transient de novo synthesis of this protein, consistent with a localisation to microglia. In vitro studies, on cultured astrocytes and microglia, demonstrated high levels of intracellular LC-1 in both cell types. LC-1 was detected in microglial but not astrocytic, conditioned media, confirming the in vivo observations that activated microglia may secrete LC-1. Our data show that at early time points following excitotoxic lesion to the cerebellum, it is activated microglia that synthesise and possibly secrete this protein, suggesting an important role of this cell type in immunosuppression and neuroprotection following damage to the central nervous system.

Animals↗
PubMed2001

13-cis-retinoic acid causes patterning defects in the early embryonic rostral hindbrain and abnormal development of the cerebellum in the macaque.

BACKGROUND: We have previously reported that exposure of embryos to 13-cis-retinoic acid (cRA) results in an abnormal phenotype of the fetal cerebellum. In this study, we analyzed early changes in the cerebellar anlagen (midbrain-hindbrain junction) as well as lesions of the fetal cerebellar vermis after a teratogenic dosing regimen of cRA in the macaque model. METHODS: We examined embryo coronal sections of the midbrain-hindbrain junction immunostained for Pax-2, Engrailed-2 (En-2) and Krox-20. To characterize the cerebellum foliation and fissure formation processes, we analyzed vermal cortical cell layer development and the number and depth of the major fissures on sagittal sections of fetal vermis. We also examined Purkinje cell development in vermal sections immunostained for CD3. RESULTS: Compared with controls, there was a consistent truncation of the midbrain-hindbrain region of early embryos exposed to cRA. The cRA-induced fetal vermis lesions included inhibition in its anteroposterior growth, altered folial patterning, a general loss of prominence of the fissures accompanied by a total loss of sublobular fissures, and changes in cortical cell layer development. CD3(+) Purkinje cells were abnormally dispersed deep into the molecular layer in the vermis. CONCLUSIONS: Our findings indicate that the effects of cRA on the developing cerebellum involve interference with the hierarchy of complex cellular and genetic interactions that lead to the growth and subdivision of the cerebellum into smaller units. The regional vermal defects may be related to early postnatal functional deficits.

Animals↗
PubMed1994

Suppression of motor cortical excitability by electrical stimulation over the cerebellum in ataxia.

We studied the effect of electrical stimulation over the cerebellum on electromyographic responses evoked by magnetic stimulation over the cerebral motor cortex in 41 normal volunteers and 32 patients with ataxia due to various disorders. In all the normal subjects, stimulation over the cerebellum significantly reduced the size of electromyographic response in the first dorsal interosseous muscle evoked by magnetic cortical stimulation, when the cerebellar stimulus preceded the cortical stimulus by 5, 6, and 7 msec. This suppression was absent or reduced in ataxic patients who had atrophy of the cerebellar hemispheres as demonstrated by magnetic resonance imaging and in patients with dysfunction of the cerebellothalamocortical pathway who had lesions in the superior cerebellar peduncle or in the motor thalamus. In contrast, suppression was normal in ataxic patients who had pontine lesions that affected the pontocerebellar afferent pathway to the cerebellum. Results were also normal in patients without cerebellar ataxia, such as those with Parkinson's disease, sensory ataxia, and cerebrovascular disease without ataxia. We conclude that electrical stimulation activates cerebellar structures that suppress motor cortical excitability through a cerebellothalamocortical pathway and that the afferent systems to the cerebellum make no or little contribution to the effect. The technique described here would be useful for distinguishing ataxia due to lesions of cerebellar afferent pathway from other types of cerebellar ataxia.

Adult↗
PubMed2002

Distribution of brain-derived neurotrophic factor and TrkB receptor proteins in the fetal and postnatal hippocampus and cerebellum of the guinea pig.

This study investigates the distribution of brain-derived neurotrophic factor protein (BDNF) and its receptor, TrkB, during the development of hippocampus and cerebellum in a long-gestation species, the guinea pig. In the granule cell populations of both structures, BDNF immunoreactivity (-IR) was exclusive to postmigratory, mature neurons. In dentate granule cells, TrkB-IR was coexpressed with BDNF-IR, suggesting that the ligand-receptor interaction could occur by means of an autocrine/paracrine mechanism. In cerebellar granule cells, TrkB-IR was detected in both pre- and postmigratory cells, indicating that immature neurons are also BDNF-responsive. With advancing gestational age an increase in the intensity of BDNF-IR in granule cells was accompanied by concomitant increases in the staining and areal growth of the associated mossy fiber layer in the hippocampus, and the molecular layer in the cerebellum. The developmental increase in BDNF- and TrkB-IR in the neuropil of both structures coincided with periods of significant growth in all strata, indicating a role for BDNF and TrkB in process outgrowth. In the hippocampus, CA2, CA3, and hilar, neurons demonstrated both BDNF- and TrkB-IR during development and maturation, whereas CA1 neurons showed TrkB-IR throughout this period but only transient BDNF-IR in early gestation. In the fetal cerebellum, Purkinje cell bodies coexpressed BDNF-IR and TrkB-IR. In the postnatal period, BDNF-IR was down-regulated but TrkB-IR persisted, indicating that mature Purkinje cells might retain their responsiveness to BDNF. Thus, we have demonstrated in both the hippocampus and cerebellum that the spatiotemporal distribution of BDNF-IR and TrkB-IR coincides with the maturation of granule cells prenatally and with significant periods of neuropil growth, both prenatally and in the immediate postnatal period.

Animals↗
PubMed2003

Afferent and efferent connections of the cerebellum of the chondrostean Acipenser baeri: a carbocyanine dye (DiI) tracing study.

The afferent and efferent connections of the cerebellum of the primitive bony fish Acipenser baeri were studied in fixed brains with a fluorescent lipophylic carbocyanine (DiI). The three regions of the cerebellum (the auricles, valvula, and corpus) showed similar afferents, mostly originated from extensive precerebellar populations of the midbrain tegmentum and from the inferior olive. A pretectal nucleus was also labeled after DiI application to the three regions of the cerebellum. However, DiI application to the pretectal region revealed that the pretectocerebellar projection mainly targeted to the caudal region of the corpus cerebelli. Some precerebellar cells were observed in the torus semicircularis, isthmic central gray, and rhombencephalic reticular formation. Primary fibers of the anterior lateral line nerve and neurons of the octavolateral area also project to the auricle. After DiI application to the auricles, most ascending efferents coursed to the region of the nucleus of the medial longitudinal fascicle and thalamus, mostly contralaterally. Ipsilateral descending fibers were also labeled in the medullary octavolateral area. Application of DiI to the nucleus of the medial longitudinal fascicle revealed three clusters of cerebellar projection neurons located in the granular layers of the auricles, valvula, and corpus cerebelli, mostly contralateral to the application site. These cerebellar projection neurons did not exhibit a number of characteristics of teleost eurydendroid cells (i.e., the cerebellar efferent cells of teleosts), such as the presence of spiny dendrites ascending to the molecular layer. Comparison of the afferent and efferent projections of the sturgeon cerebellum with those reported in teleosts supports the hypothesis that some traits observed in the teleost cerebellar system represent recent evolutionary developments.

Afferent Pathways↗
PubMed2005

Developmental modifications of olivocerebellar topography: the granuloprival cerebellum reveals multiple routes from the inferior olive.

Correct function of neural circuits depends on highly organized neuronal connections, refined from less precise projections through synaptic elimination, collateral regression, or neuronal death. We examined regressive phenomena that define olivocerebellar topography during maturation from Purkinje cell polyinnervation to monoinnervation. We used bilateral retrograde tracing to determine the source of olivocerebellar afferents to posterior vermis lobules VII-VIII in a model of retained immature Purkinje cell polyinnervation, the granuloprival cerebellum. In controls, labelled neurons were found only in the contralateral inferior olive (ION) clustered in a small ventromedial locus that is congruent with known olivocerebellar topography. In granuloprival animals, olivary labelling appeared more dispersed and was present in homologous ipsilateral regions. Double-labelled neurons were never seen. Retrograde tracing following unilateral olivocerebellar transection in adult granuloprival rats revealed: 1) the origin of the normal (remaining) path projecting through the contralateral inferior peduncle was more localized than in irradiated nonpedunculotomized rats, 2) a small double-crossed path, and 3) a projection that ascends the peduncle ipsilateral to the ION of origin, part of which crosses the midline within the cerebellum. Electrophysiological and immunohistochemical assessment in the neonatal cerebellum revealed that transcommissural paths are not present during development but sprout within the irradiated cerebellum. Therefore, the olivocerebellar projection in the granuloprival rat, as a model of the immature path, shows parasagittal organization similar to that of controls in its normally crossed path but possesses additional abnormal projections. Thus, maturation of olivocerebellar topography involves removal of whole developmental paths to define laterality plus synapse elimination within largely predefined parasagittal zones.

Animals↗
PubMed2006

Cell morphology and circuitry in the central lobes of the mormyrid cerebellum.

The cerebellum of mormyrid electric fish is large and unusually regular in its histological structure. We have examined the morphology of cellular elements in the central lobes of the mormyrid cerebellum. We have used intracellular injection of biocytin to determine the morphology of cells with somas in the cortex, and we have used extracellular placement of anterograde tracers in the inferior olive to label climbing fibers. Our results confirm previous Golgi studies and extend them by providing a more complete description of axonal trajectories. Most Purkinje cells in mormyrids and other actinopterygian fishes are interneurons that terminate locally in the cortex on efferent neurons that are equivalent to cerebellar nucleus cells in mammals. We confirm the markedly sagittal distribution of the fan-like dendrites of Purkinje cells, efferent cells, and molecular layer interneurons. We show that Purkinje cell axons extend further than was previously thought in the sagittal plane. We show that climbing fibers are distributed in narrow sagittal strips and that these fibers terminate exclusively in the ganglionic layer below the molecular layer where parallel fibers terminate. Our results together with those of others show that the central lobes of the mormyrid cerebellum, similar to the mammalian cerebellum, are composed of sagittally oriented modules made up of Purkinje cells, climbing fibers, molecular layer interneurons, and cerebellar efferent cells (cerebellar nucleus cells in mammals) that Purkinje cells inhibit. This modular organization is more apparent and more sharply defined in the mormyrid than in the mammal.

Animals↗
PubMed1977

Experimental analysis of embryogenesis of cerebellum in rat. II. Morphogenetic malformations following x-ray irradiation on day 18 of gestation.

Rat embryos of 18 days gestation were exposed in utero to 170 R of X-ray irradiation. Embryos were collected six hours, 1, 2, and 3 days after irradiation, and animals of 2-, 6-, 15- and 30-day-old postnatal age were sacrificed. Six hours after irradiation pyknosis of cells was notices in the external granular layer along the posterior aspect of the cerebellum. Neuroblasts, destined to differentiate into Purkinje cells, were found arrested in their migratory path. During subsequent periods of embryogenesis the external granular layer was found recovered, and clustering of the neuroblasts were disorganized and fragmented. This abnormal clustering of neuroblasts was permanent, and the external granular layer followed the same abnormal pattern in its growth. During postnatal development the internal granular layer also was found to follow the abnormal pattern of Purkinje cell layer. These abnormal developmental events were seen to lead to malformed folia in the anterior regions of the cerebellum. In addition to it the cerebellum of X-ray irradiated animals appeared smaller than the normal. Issues having a bearing on the differential radiosensitivity of different cells, factors determining the small size of the cerebellum, and cellular events determining the morphogenetic malformations are discussed.

Animals↗
PubMed1980

Strain-specific variations in the folial pattern of the mouse cerebellum.

The folial pattern of the mouse cerebellum was compared in 13 inbred strains and a closed colony. The morphological variation of the cerebellum among individual animals was slight within each inbred strain, whereas it was marked in the closed colony. There was no sex-related difference in the cerebellar folial pattern. The cerebellum of mice from each inbred strain presented a characteristic folial pattern in which some similarities were recognized among animals from genetically related strains. These findings revealed that the morphological variation in the folial pattern of the cerebellum was strain-specific in mice and had an intimate connection with the genetic control.

Animals↗
PubMed1980

Temporal and spatial patterns of Purkinje cell formation in the mouse cerebellum.

In an attempt to determine the time of origin and the final localization of Purkinje cells in the cerebellum, pregnant mice were injected with tritiated thymidine successively, four to six times daily, beginning on either day 10, 11, 12, 12.5, 13, or 14 of gestation, considering 6 a.m. on the day when vaginal plugs were found as day 0. Offspring were killed at 30 days of age, and serial sagittal sections of the cerebellum were prepared for autoradiography. Labeled and unlabeled Purkinje cells in the various regions of the cerebellum were counted, and unlabeled ones were considered to be formed earlier than the initiation of the injections. In the medial level of the vermis, the majority of the Purkinje cell population was formed on day 12 of gestation and a few on day 13, whereas the cells in the paravermian and hemispheric portions were formed on days 11 and 12. Thus, a slight lateromedial gradient of the time of Purkinje cell origin was demonstrated. Purkinje cells that were formed after day 12.5 were distributed more in the vermis than in the hemisphere, more in the ventral region of the vermis (lingula, ventral lobule of lobulus centralis, and nodulus) than in the dorsal region (culmen, declive, tuber, pyramis, and uvula), and deep in the vermian fissures, rather than on the surface of the lobules. These findings suggest that postnatally, early maturing regions of the cerebellum may have received many of the later formed Purkinje cells.

Animals↗
PubMed1982

Afferent connections of the cerebellum in various types of reptiles.

The origin of cerebellar afferents was studied in various types of reptiles, viz., the turtles Pseudemys scripta elegans and Testudo hermanni, the lizard Varanus exanthematicus, and the snake Python regius, with retrograde tracers (the enzyme horseradish peroxidase and the fluorescent tracer "Fast Blue"). Projections to the cerebellum were demonstrated from the nucleus of the basal optic root, the interstitial nucleus of the fasciculus longitudinalis medialis, the vestibular ganglion, and the vestibular nuclear complex, two somatosensory nuclei, viz., the descending nucleus of the trigeminal nerve and the nucleus of the dorsal funiculus, the nucleus of the solitary tract, the reticular formation, and throughout the spinal cord. A distinct bilateral projection to the cerebellum was found to arise in a nucleus previously called nucleus parvocellularis medialis (Ebbesson, '67). In the present study this cell mass is termed the perihypoglossal nuclear complex, considering its comparable position and fiber connections to the perihypoglossal nuclei in mammals. In all reptilian species studied a contralateral cerebellar projection of a cell mass located in the caudal brainstem adjacent to the nucleus raphes inferior was observed. It seems likely that this cell mass represents the reptilian homologue of the mammalian inferior olive. Most of the spinocerebellar fibers appeared to arise in neurons located in area VII-VIII of the gray matter. In this respect the origin of the spinocerebellar projection in reptiles resembles the origin of the rostral and ventral spinocerebellar tracts in mammals. No indications for the existence of a column of Clarke or a central cervical nucleus in the reptilian spinal cord were obtained. On comparison of the cerebellum afferents in reptiles with the known connections of the cerebellum in amphibians, birds, and mammals, a basic pattern of cerebellar afferent projections appears to exist in these vertebrate classes, including retinal, vestibular, precerebellar, somatosensory, and spinal afferents.

Afferent Pathways↗