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At least 19 recordsLinked to original sources

The cerebellum: it's about time! But timing is not everything--new insights into the role of the cerebellum in timing motor and cognitive tasks.

Converging evidence from different research studies supports a role for the cerebellum in timing neural processes. The cerebellum is part of a distributed system for motor control. The timing hypothesis provides a specific functional role for the unique contribution of the cerebellum. The timing capabilities of the cerebellum appear to extend beyond motor control into tasks focusing on perceptual processing that require the precise representation of temporal information and sensorimotor learning. Behavioral and modeling studies suggest that the cerebellar timing system is best characterized as providing a near-infinite set of interval-type timers rather than as a single clock with pacemaker or oscillatory properties, but this is controversial. In addition to learning precisely timed motor responses, the cerebellum is involved in on-line processing using feed-forward systems for which sensory input is used prior to movement execution to improve movement accuracy. This would be a mechanism for triggering accurate "time." The cerebellum continues to fascinate scientists, and although survival is possible without the cerebellum, the resultant quality of life is significantly compromised with clumsiness, ataxia, hypotonia, dysarthria, slowing of various cognitive perceptual processes, and impaired fine motor and ocular-motor coordination. The last three decades have seen the development of research that has focused on how the cerebellum functions. Further neurophysiologic research in cerebellar cortical neurotransmission is likely to further our understanding of the cerebellar contribution to timing sensorimotor processes.

Animals↗

Role of the cerebellum in reaching movements in humans. II. A neural model of the intermediate cerebellum.

The cerebellum is essential for the control of multijoint movements; when the cerebellum is lesioned, the performance error is more than the summed errors produced by single joints. In the companion paper (Schweighofer et al., 1998), a functional anatomical model for visually guided arm movement was proposed. The model comprised a basic feedforward/feedback controller with realistic transmission delays and was connected to a two-link, six-muscle, planar arm. In the present study, we examined the role of the cerebellum in reaching movements by embedding a novel, detailed cerebellar neural network in this functional control model. We could derive realistic cerebellar inputs and the role of the cerebellum in learning to control the arm was assessed. This cerebellar network learned the part of the inverse dynamics of the arm not provided by the basic feedforward/feedback controller. Despite realistically low inferior olive firing rates and noisy mossy fibre inputs, the model could reduce the error between intended and planned movements. The responses of the different cell groups were comparable to those of biological cell groups. In particular, the modelled Purkinje cells exhibited directional tuning after learning and the parallel fibres, due to their length, provide Purkinje cells with the input required for this coordination task. The inferior olive responses contained two different components; the earlier response, locked to movement onset, was always present and the later response disappeared after learning. These results support the theory that the cerebellum is involved in motor learning.

Arm↗

TNF-alpha in cerebral cortex and cerebellum is affected by amygdalar kindling but not by stimulation of cerebellum.

One group of male Wistar rats was kindled by electrical stimulation (ES) of the amygdala, one group was sham operated, while other rats were stimulated in the paleocortex of the cerebellum. The kindled generalized clonictonic seizures were followed by a net increase of the tumor necrosis factor-alpha (TNF-alpha) content both in the cerebral cortex (from 34.7 +/- 6.0 to 76.7 +/- 6.9 pg/mg of wet brain tissue) and cerebellum (from 106.6 +/- 17.7 to 193.8 +/- 29.8 pg/mg of wet tissue) in comparison with the data from sham-operated animals. This effect was observed 24 h after the induction of the last kindled seizures. ES of the cerebellum (100 Hz) was not followed by any changes in TNF-alpha content in the cortex and cerebellum. Moreover, kindling was not followed by any changes in thiol/disulfide system, but ES of the paleocerebellum induced an increase in free thiol groups in the cortical tissue. It can be concluded that the increase in TNF-alpha content is specific for the kindling process and that the antiepileptic effects of cerebellar ES might be realized via an intensification of antioxidative processes in the neural tissue.

Amygdala↗

Effects of cations on binding, in membrane suspensions, of various opioids at mu-sites of rabbit cerebellum and kappa-sites of guinea-pig cerebellum.

At the mu-sites of rabbit cerebellum, NaCl, LiCl, KCl, choline chloride and MnCl2 were tested for potentiation and inhibition of the binding of several opioids. Naloxone, (-)-bremazocine and diprenorphine are mu-antagonists in pharmacological assays and their binding is potentiated by the lower concentrations and inhibited by the higher concentrations of NaCl. The binding of the agonists [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin and [3H]-dihydromorphine is inhibited. MnCl2 potentiates the binding of the agonist [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin but not the binding of the antagonists. The thresholds of inhibition and slopes of the dose-response curves for inhibition by MnCl2 and LiCl vary. This finding may indicate that potentiating effects of MnCl2 and LiCl are masked by simultaneous inhibition. At the kappa-sites of guinea-pig cerebellum, NaCl, KCl and MnCl2 inhibit the binding of [3H]-dynorphin A (1-8), [3H]-dynorphin A (1-9), [3H]-(-)-bremazocine, [3H]-tifluadom, and [3H]-diprenorphine. NaCl also causes a small potentiation of the binding of [3H]-diprenorphine, which is a kappa-agonist in the guinea-pig myenteric plexus but a kappa-antagonist in the rabbit vas deferens. The slopes of the inhibitory dose-response curves and the thresholds of inhibition vary with the different ligands. Therefore some potentiating effects may have been masked. The results support the view that NaCl, and perhaps LiCl, but not KCl and choline chloride, potentiate the binding of mu-antagonists but not the binding of mu-agonists. It is not yet possible to decide whether, at the kappa-site, there is a similar differentiation of the binding of agonists and antagonists.

Animals↗

Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.

Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.

Animals↗

[Transplantation of embryonal cerebral cortex to the adult rat cerebellum: the fiber connections made by cortical transplants and the cerebellum].

Fifteen-day-old embryonic neocortical tissue was transplanted into the mature cerebella of normal adult rats (Fischer 344) heterotopically. After 5-8 months, WGA-HRP was injected into the host inferior olivary nucleus, pontine raphe, pontine nuclei, and neocortical transplants, 0.3 microliter, 0.2 microliter and 0.05 microliter respectively. The animals were sacrificed 48 hours later, and the HRP positive neuron and nerve fibers were examined in the transplants and host brain stem. Other animals were sacrificed for anti-dopamine-beta-hydroxylase immunohistochemical study and electron microscopic observation. Anterograde and retrograde tracing methods with the HRP method revealed on the light microscopic level that the transplants had received afferents from the host's locus coeruleus, and the inferior olivary nucleus. In one case, HRP injected into the host inferior olive was almost limited within the inferior olivary nucleus. Therefore, HRP-labelled fibers in the cerebellum were thought to be climbing fibers. The climbing fibers from the host inferior olivary nucleus entered the transplant from the host cerebellar medullary layers and branched in the transplant. The fiber ingrowth was limited within 300-500 microns for the distance. In another case, HRP injected into the inferior olive extended to the lateral reticular and the pontine nuclei. HRP labelled fibers entered the graft from the host medullary layers and many granular patterns like axon terminals were observed in the graft. In cases, in which HRP was injected into the pontine raphe and pontine nuclei, HRP labelled fibers did not grow into the graft. Retrograde tracing method with HRP injected into the graft showed labelled neurons in the host locus coeruleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

Destruction of meningeal cells over the newborn hamster cerebellum with 6-hydroxydopamine prevents foliation and lamination in the rostral cerebellum.

Intracisternal injection of 30 micrograms 6-hydroxydopamine was used to destroy meningeal cells in the newborn hamster. After 20 or 30 days the cerebella of treated animals showed severe morphological alterations including: an absence of distinct folia anterior to the primary fissure; a disruption of lamination in the same region by the displacement of both Purkinje cells and cerebellar interneurons; a reduction in size and frequency of branching of the medullary tree with anomalous anterobasal branches and splaying; reductions in the area of the molecular layer, the total area occupied by granule cells, the length of the pial surface and the length of the Purkinje cell layer of 29, 21, 57 and 27%, respectively; disorganization of the radially organized glial scaffold by outgrowth of Bergmann glial fibers and displacement of their cell bodies, the Golgi epithelial cells, and anomalous orientation, polarity, size and branching frequency of Purkinje cell dendritic trees. These findings support our earlier hypothesis that the initial destruction of meningeal cells destabilizes the cerebellar surface (basal lamina and glia limitans superficialis) and disorganizes the glial scaffold, while the neuronal cerebellar malformations are secondary to this glial defect.

Aging↗

Cadherin-defined segments and parasagittal cell ribbons in the developing chicken cerebellum.

In the developing chicken cerebellar cortex, three cadherins (Cad6B, Cad7, and R-cadherin) are expressed in distinct parasagittal segments that are separated from each other by ribbons of migrating interneurons and granule cells which express R-cadherin and Cad7, respectively. The segment/ribbon pattern is respected by the expression of other types of molecules, such as engrailed-2 and SC1/BEN/DM-GRASP. The cadherin-defined segments contain young Purkinje cells which are connected to underlying nuclear zones expressing the same cadherin, thereby forming parasagittal cortico-nuclear zones of topographically organized connections. In addition, R-cadherin-positive mossy fiber terminals display a periodic pattern in the internal granular layer. In this layer, Cad7 and R-cadherin are associated with synaptic complexes. These results suggest that cadherins play a pivotal role in the formation of functional cerebellar architecture by providing a three-dimensional scaffold of adhesive information.

Animals↗

Modified composition of major ontogenetically regulated mRNAs and proteins in the cerebellum of old and of staggerer mice.

The macromolecular composition of the cerebellum was examined in young and old mice, and in staggerer mutant mice, as compared with their background control strain. We examined the in vitro translation products of cerebellum mRNA, which reflect the biosynthetic potential of cell bodies endogenous to the cerebellum. Simultaneously, we examined the composition of the major cerebellum proteins, which includes the contribution of incoming fibers, in addition to the proteins composing cerebellar cells. Changes in the concentrations of various major proteins and a significant reduction in the translational efficiency of RNA were observed in the cerebellum of old BALB/c mice. This reduction probably does not reflect a specific damage to interneurons, since RNA from the cerebellum of 5-month-old staggerer mice was as efficient in translation in vitro as RNA from the cerebellum of mice from C57B6J normal background strain. Several of the major cerebellar proteins were identified by 2-dimensional gel electrophoresis. Changes were observed at the level of and the microheterogeneity of tubulin from the cerebellum of old, as compared with young mice. The aging-related modifications in cerebellar tubulin may be regulated at the level of mRNA, since mRNA from the cerebellum of old mice appeared to produce lower amounts of a polypeptide band co-migrating with tubulin. When compared with translation products directed by mRNA from normal cerebellum, most of the major identified polypeptides produced by mRNA from staggerer cerebellum showed marked differences in their relative intensity. Thus, this mutation appears to change the composition of cerebellar mRNA. These differences were analyzed together with previously obtained data on the composition of translation products during development of normal and of irradiation-agranulated cerebellum. The combined analysis of cerebellar mRNA products permits us to tentatively assign defined protein markers to specific cerebellar cell types and periods in development.

Aging↗

Synaptic junctions isolated from cerebellum and forebrain: comparisons of morphological and molecular properties.

Synaptic junction (SJ) fractions have been isolated from rat cerebellum which are similar to forebrain SJs on the basis of morphology and enrichment of synaptic structures. The polypeptide compositions of SJ fractions were analyzed by one- and two-dimensional SDS-gel electrophoresis and stained by the silver technique. Equivalent numbers of proteins that possess similar relative mobilities (Mr), isoelectric points and staining intensities were present in cerebellum and forebrain synaptic fractions. A few prominent differences were observed between cerebellum and forebrain synaptic fractions; cerebellum SJs contained a 240 K protein that was not detected in the forebrain and the 52,000 K, major PSDp protein was present in forebrain SJs in amounts that are approximately 5-fold greater than in cerebellum SJ fractions. The identity of the cerebellum mPSDp was verified by electrophoretic mobility, peptide fingerprinting and [125I]calmodulin binding. Differences between various synaptic fractions in mannose containing glycoproteins were examined by the binding of [125I]concanavalin A (Con A) to gels. On the basis of apparent molecular weights, the glycoproteins in forebrain and cerebellum SPMs were very similar. In contrast, however, the prominent glycoproteins that reside in the postsynaptic junctional membrane of forebrain SJs were undetectable in SJ fractions isolated from cerebellum. SJ fractions from cerebellum contained their own distinct group of Con A binding glycoproteins. SPM and SJ fractions from forebrain and cerebellum were examined for receptors for excitatory (aspartate, glutamate and kainic acid) and inhibitory (GABA) neurotransmitters and the benzodiazepine analog flunitrazepam. On the basis of relative receptor contents, SJ fractions isolated from either brain region were qualitatively similar and bound significant amounts of excitatory and inhibitory transmitters. These findings support the notion that SJs from cerebellum contain a distinct class of synaptic elements that are in large part derived from asymmetric, type I synapses.

Animals↗