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PubMedDate not supplied

Single-unit evidence for eye-blink conditioning in cerebellar cortex is altered, but not eliminated, by interpositus nucleus lesions.

Many theories of motor learning explain learning-related changes in motor behavior in terms of plasticity in the cerebellar cortex. Empirical evidence, however, does not always appear to be consistent with such formulations. It is the anterior cerebellar interpositus nucleus (aINP) that seems to be essential for acquisition and retention of conditioned eye-blink responses under most circumstances and it has been therefore suggested that the aINP is the critical site of learning-related plasticity during eye-blink conditioning. Supporting this conclusion are studies demonstrating that multiple-unit conditioning-related neural activity patterns observed in many brain regions disappear after aINP lesion. The possibility that the cerebellar cortex may be involved in forming these patterns has not been assessed adequately, however. In the current study, trained rabbits received kainic acid lesions of the INP. After recovery, the animals underwent additional sessions of conditioning during which single-unit activity was recorded from the cerebellar cortex. Our results suggest that the aINP is not the sole site of plasticity during eye-blink conditioning, as a subset of the neurons recorded from lesioned animals demonstrated conditioning-related firing patterns. The lesions did change the character of these firing patterns from those observed in saline controls, however, in ways that can be generally described as a loss of organization. The normal tendency for the population of cortical cells to change firing rate together, for instance, was significantly less noticeable in lesioned animals. These results suggest that the aINP may be involved in the production of important features of conditioned responding, such as system timing function, therefore suggesting the need for more models that incorporate aINP and brain stem feedback as integral to the production of organized neural and behavioral responses.

Acoustic Stimulation↗
PubMed1997

Light and electron microscopic demonstration of mGluR5 metabotropic glutamate receptor immunoreactive neuronal elements in the rat cerebellar cortex.

The cellular and subcellular localization of the mGluR5 metabotropic glutamate receptor subtype was studied in the rat cerebellar cortex, by using the preembedding immunoperoxidase and immunogold techniques. Light microscopic observations revealed an abundant, intense labeling of neurons in the granular layer as well as in the molecular layer. Lugaro and Golgi cells exhibited an intense mGluR5 immunoreactivity, while only a fraction of the neurons in the molecular layer were found to be mGluR5 immunopositive. In addition to a dense plexus of immunoreactive dendrites in the molecular layer of the cerebellar cortex, the mGluR5 immunopositive Golgi cell dendrites resembling axons at the light microscopic level were also labeled in the granular layer. At the ultrastructural level, mGluR5 immunoreactivity was present in neuronal elements postsynaptic to axon terminals of different morphology. By using a pre-embedding immunogold method, it was found that mGluR5 immunoreactivity is accumulated at the plasma membranes extrasynaptically as well as at the periphery of the postsynaptic specializations, mainly of the parallel fiber synaptic contacts. These findings provide morphological evidence that mGluR5 is expressed by a population of neurons in the cerebellar cortex and can synaptically be activated via the parallel fiber system.

Animals↗
PubMedDate not supplied

Detection of sequences in the cerebellar cortex: numerical estimate of the possible number of tidal-wave inducing sequences represented.

The two major cortices of the brain--the cerebral and cerebellar cortex--are massively connected through intercalated nuclei (pontine, cerebellar and thalamic nuclei). We suggest that the two cortices co-operate by generating precise temporal patterns in the cerebral cortex that are detected in the cerebellar cortex as temporal patterns assembled spatially in the mossy fibers. We will begin by showing that the tidal-wave mechanism works in the cerebellar cortex as a read-out mechanism for such spatio-temporal patterns due to the synchronous activity they generate in the parallel fiber system which drives the Purkinje cells--the output neurons of the cerebellar cortex--to fire action potentials. We will review the anatomy of the mossy fibers and show that within a "beam", or "row" of cerebellar cortex the mossy fibers in principle could embed a vast number of tidal-wave generating sequences. Based on anatomical data we will argue that the cerebellar mossy fiber-granule cell-Purkinje cell system can potentially detect and--through learning--select from an enormous number of spatio-temporal patterns.

Animals↗
PubMed2003

Antigenic compartmentation of the cat cerebellar cortex.

Despite the apparent uniformity in cellular composition of the mammalian cerebellar cortex, a complex topography is revealed by several expression patterns. Zebrin II, a polypeptide antigen identified as aldolase C, is one such marker which, in several species of mammals, is restricted to a subset of Purkinje cells that are clustered together to form a symmetrical and reproducible array of zones and stripes. In rodents the cerebellar cortex is divided into four transverse zones--anterior, central, posterior, and nodular. Each transverse zone is further subdivided mediolaterally into an array of parasagittal stripes. The similar zone and stripe organization partitions the hemispheres. Based upon a novel whole mount immunohistochemical staining procedure, we have now identified homologous zones and stripes in the feline cerebellum. In the cat cerebellum the somata of most Purkinje cells express zebrin II but parasagittal stripes may still be delineated owing to the alternating high and low zebrin II expression levels in the dendritic arbors. As in rodents, the cat cerebellum consists of four transverse zones with each zone subdivided into a unique combination of zebrin II parasagittal stripes, suggesting that a common architecture underlies the organization of the mammalian cerebellum.

Animals↗
PubMed1994

Effect of treatment with the dihydropyridine-type calcium antagonist darodipine (PY 108-068) on the expression of neurofilament protein immunoreactivity in the cerebellar cortex of aged rats.

The effect of long-term treatment with the dihydropyridine-type Ca2+ antagonist darodipine (PY 108-068) on the expression of neurofilament (NF) protein (200 kDa-NF subunit) immunoreactivity in the cerebellar cortex of aged male Wistar rats was assessed using immunohistochemical techniques associated with image analysis. In 12-month-old rats (adult) used as reference animals, 200 kDa-NF subunit immunoreactivity was observed primarily in axons of basket neurons localized in the molecular layer and surrounding the cell body of Purkinje neurons. A specific immunoreactivity was also found in the initial segment of Purkinje neuron axons, and in axons of the white matter of the cerebellar cortex. In 24-month-old rats (aged) a significant decrease in the area occupied by immunoreactive structures was noticeable in comparison with adult animals. A 6-month treatment (from the 18th to the 24th month of life) with an oral daily dose of 10 mg/kg of darodipine restored in part the expression of 200 kDa-NF subunit immunoreactivity in the cerebellar cortex. These data indicate that treatment with the dihydropyridine-type Ca2+ channel blocker darodipine is able to counter in part the age-related loss in the expression of NF protein in the rat cerebellar cortex. This suggests that darodipine may reduce neuronal cytoskeletal changes occurring in aging and in neurodegenerative disorders.

Aging↗
PubMed1976

Undernutrition and the developing cerebellar cortex in the rat.

Undernutrition of the newborn rats, produced during the first 3 weeks by increasing the litter size and restricting the mother's diet, resulted in reduction of the body and brain weights of the experimental animals. One group of undernourished animals showed especially severe reduction of body and cerebellar weights. These animals, on the 10th postnatal day, had an immature cerebellar cortex corresponding to that of the 7th day postnatal control animals. The external granular layer persisted in the cerebellar cortex of the underweight animals until the 23rd day, while it disappeared by 20th day in the control animals. Mitotic activity was evident until the 21st postnatal day in these animals while it stopped in the normal animal by 16th postnatal day. There was no marked difference in the fine structure of the various cell types in the control and undernourished animals. Midsagittal tracings of the cerebellar cortex showed a reduced surface area in the undernourished animals, while the thickness of the external granular layer and molecular layer did not show any significant difference when compared to that of the control animals, thus showing a reduction in total cell number, but not per unit area. The normal morphological appearance of the cerebellar cortex in the underfed animals of higher weight probably indicates that these animals are adequately nourished in spite of the reduction in weight when compared to the control animals, which probably are overfed.

Animals↗
PubMed1993

Effects of hyperbilirubinaemia on glutathione S-transferase isoenzymes in cerebellar cortex of the Gunn rat.

The glutathione S-transferases (GSTs) are a family of isoenzymes involved in the detoxication of a variety of electrophilic xenobiotics. The present investigation demonstrates that GST activity and the concentration of cytosolic GSTs in cerebellar cortex of Gunn rats were increased in hyperbilirubinaemic animals compared with non-jaundiced controls. Age-dependent and region-specific increases in GST isoenzymes were seen in three regions of the cerebellar cortex of jaundiced Gunn rats, whereas GST concentrations were not altered in the brainstem, thalamus/hypothalamus, cortex or liver. Cytosolic GST activity was increased 1.3-fold in the flocculus and lateral hemispheres of 20-day-old and 1.7-fold in the flocculus, lateral hemispheres and vermis of 60-day-old jaundiced (jj; homozygous) Gunn rats compared with non-jaundiced (Jj; heterozygous) Gunn rats. H.p.l.c. was used to determine the GST subunit protein concentrations in cytosolic fractions isolated from liver and brain regions of jaundiced and non-jaundiced animals. In all regions of the cerebellum from 20-day-old animals, the levels of Alpha-class GST subunits 2 (Yc1; 3.0-fold) and 8 (Yk; 2.0-fold) were increased in jaundiced rats. In 60-day-old animals, the concentrations of Alpha-class GST subunits 2 (Yc1; 5.0-fold) and 8 (Yk; 3.0-fold), Mu-class subunit 11 (Yo; 2.5-fold) and Pi-class subunit 7 (Yp; 2.0-fold) were increased in all regions of cerebellar cortex of jaundiced animals. In cerebellum of 10-, 20- and 60-day-old non-jaundiced and jaundiced Gunn rats, the flocculus had the highest concentration of Mu-class GST subunit 4 (Yb2) and vermis the lowest; hyperbilirubinaemia increased the concentration of subunit 4 (Yb2; 3- to 5-fold) in the flocculus and lateral hemispheres, but not the vermis, of 20- and 60-day-old rats. Intraperitoneal injection of sulphadimethoxine, a long-acting sulphonamide which displaces bilirubin from its albumin-binding sites and increases the bilirubin levels in tissues, further increased the already elevated concentrations of GST subunits in the lateral regions of cerebellar cortex of hyperbilirubinaemic rats. For example, the concentration of subunit 4 (Yb2) was increased 2.2-fold (compared with non-jaundiced controls) in Gunn rats injected with saline and 7.4-fold in rats injected with 100 mg of sulphadimethoxine/kg body weight. In contrast, GSTs in the vermis of jaundiced animals were not affected by sulphadimethoxine injection. Sulphadimethoxine had no effect on GST concentrations in lateral regions and vermis of heterozygous (Jj) Gunn rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed2004

Intermittent hypoxia damages cerebellar cortex and deep nuclei.

Obstructive sleep apnea patients show cerebellar cortex and deep nuclei gray matter loss, a possible consequence of intermittent hypoxia (IH) accompanying the syndrome. We exposed Sprague-Dawley rats (n=24) to room air only or 10.3% O2, balance N2, alternating every 480 s (240 s duty cycle) with room air for 5, 10, 15, 20 or 30 h (7.5 h per day) during light periods. IH-exposed rats showed increased numbers of damaged Purkinje cells (31.1, 50.5, 54.7, 65.2, and 94.4% for 5, 10, 15, 20 and 30 h groups, respectively; p<0.001 for slopes of the total, swollen/autolysed, and shrunken/dark cell counts), as assessed by hematoxylin and eosin staining. Anti-caspase-3 antibody density increased in the fastigial nuclei subsequent to 5-h exposure. Short-term IH exposure elicits dose-dependent cerebellar Purkinje and fastigial neuron damage.

Animals↗
PubMed1989

Observations on the projection from the perihypoglossal nuclei to the cerebellar cortex and nuclei in the cat. A retrograde WGA-HRP and fluorescent tracer study.

The origin and distribution of cerebellar cortical and nuclear afferents from the perihypoglossal nuclei have been studied by means of retrograde transport after implants and injections of the wheat germ agglutinin-horseradish peroxidase complex in the cat. The projection reaches all the cerebellar nuclei as well as vermal, intermediate and lateral parts of the cerebellar cortex. It is bilateral with an ipsilateral predominance and originates from all the perihypoglossal nuclei. The majority of the projecting neurons are situated caudally in the nucleus prepositus, while smaller numbers of projecting neurons are located in the rostral part of this nucleus, in the rostral nucleus intercalatus and in the nucleus of Roller. Small and medium-sized spindle-shaped to round cells located throughout the nucleus prepositus and in the rostral nucleus intercalatus have widespread projections, reaching all parts of the cerebellar cortex and nuclei, whereas large multipolar cells located in the caudal ventromedial part of the nucleus prepositus and in the nucleus of Roller have projections only to the flocculus and nodulus and the lateral and intermediate cortices. Retrograde fluorescent double-labelling experiments were made to investigate possible axonal branching of the perihypoglosso-cerebellar fibres. In experiments with injections of rhodamine-B-isothiocyanate (RITC) in the left cerebellar hemisphere and implants of crystalline Fluoro-Gold in the right hemisphere, single- and double-labelled cells were found intermingled throughout the perihypoglossal nuclei. Experiments with cerebellar cortical injections of RITC and implants of crystalline Fluoro-Gold in the underlying nucleus, demonstrated single- and double-labelled cells in the nucleus prepositus and the rostral nucleus intercalatus, while only single-labelled RITC neurons were seen in the group of large neurons in the ventromedial part of the nucleus prepositus and the nucleus of Roller. After injections of RITC in the cerebellar cortex and implants of crystalline Fluoro-Gold in the abducent nucleus on the same side, double-labelled neurons were found only in the rostral nucleus prepositus.

Afferent Pathways↗
PubMed1998

Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats.

In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT2 receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a similar decrease in AT2 receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1 receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT2 receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT2 receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the development of this pathway.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1994

An experimental scanning electron microscopic study of human cerebellar cortex using the t-butyl alcohol freeze-drying device.

Specimen preparation methods are very important in scanning electron microscopy (SEM) of nerve tissues. In the present study, a t-butyl alcohol freeze-drying device was used to prepare cerebellar cortex of the human and that of the rat at 15 degrees C and 160 mm Hg. This method has been previously used with success in the preparation of other tissues, such as pancreas and trachea. Relatively large specimens (about 10 mm x 15 mm x 1 mm) of formalin-fixed human and glutaraldehyde-Millonig buffer perfused (1 hour) Wistar rat were rinsed in water, dehydrated in a series of ethanols, immersed in t-butyl alcohol, and then placed in the new freeze-drying device. The specimens were cut with a razor, freeze-dried without acid or alkali digestion, mounted on stubs, and sputter-coated with gold. This new preparation method allowed a higher magnification examination of surfaces of cells and fibers of the human cerebellar cortex compared to the critical point drying method. This was valid for Purkinje cell bodies with axons, dendrites with climbing fibers and climbing fiber glomeruli, and stellate neuron cell processes connected to the Purkinje cell dendrites. Lugaro cell, basket cells with axons, Golgi II cell, mossy fiber glomerulus with granule cell dendrites, satellite Bergmann glial cells with processes, and many microtubule-like fibrous structures on the inside of Purkinje cell dendrites were observed. Furthermore with this method, the glutaraldehyde-Millonig buffer perfused cerebellar cortex of the Wistar rat shows better three-dimensional images than the formalin-fixed human cerebellar cortex.

Aged↗
PubMed1985

Do hypothalamo-cerebellar fibres terminate in all layers of the cerebellar cortex?

The terminal distribution of hypothalamo-cerebellar fibres has been studied with anterograde transport of the wheat germ agglutinin-horseradish peroxidase complex in the cat and rat. The hypothalamo-cerebellar fibres appear to enter all three layers of the cerebellar cortex. Anterogradely labelled branching axons were found in the granular layer and near the Purkinje cell perikarya. In addition, anterogradely filled hypothalamo-cerebellar axons could be traced into the molecular layer, where they ramified. The branches ran parallel to the long axis of the folia, resembling parallel fibres. Our findings give evidence that the hypothalamo-cerebellar fibres are neither mossy fibres nor climbing fibres, but represent a third type of cerebellar cortical afferents. Fibres of this third category are tentatively called multi-layered fibres. It appears from the literature that some other cerebellar afferent projections show the same general pattern of cortical terminal distribution.

Afferent Pathways↗
PubMed2005

Oscillations in the cerebellar cortex: a prediction of their frequency bands.

Local recurrent connections endow the cerebellar cortex with an intrinsic dynamics. We performed computer simulations to predict the frequency bands of the oscillations that will most likely emerge. Feedback inhibition from the Golgi to the granule cells induced 10-50 Hz oscillations, the period at resonance being approximately equal to four times the maximum conduction delay generated along the parallel-fiber connections from granule to Golgi cells. In the molecular layer, the interneurons tended to induce fast oscillations (100-250 Hz), having a period equal to about four times the delay over their reciprocal synaptic connections. Finally, although the presence of lateral inhibition among the Purkinje cells has not been firmly established, reciprocal Purkinje-cell synapses are predicted to transform the cerebellar cortex into a potential temporal integrator.

Animals↗
PubMed1999

[Localization of NO-synthase in Lugaro cells and mechanisms of NO-ergic interactions between inhibitory interneurons of rabbit cerebellar cortex].

Using histochemical demonstration of NADPH-diaphorase (NADPH-d), several types of NO-producing cells were revealed in rabbit cerebellar cortex. Stellate and basket neurons of molecular layer, Golgi complex and white matter neurons are NADPH positive, while Purkinje cells are negative to NADPH-d. NADPH-d-positive granule cells are found in paraflocculus and flocculus, in vermis and paramedian lobules. They contain predominantly low enzyme activity or are not stained at all. In all the cerebellar cortex areas fusiform Lugaro cells lying under Purkinje cell bodies are stained intensely. Their horizontal dendrites are oriented parallel to Purkinje cells layer. Lugaro cells forming local axonal plexus in lower third of molecular layer and large Lugaro cells with the axon descending to granular layer and basket cell axons form contacts with Lugaro cell dendrites. Clusters of NADPH-d diaphorase positive cells were demonstrated. Dendrosomatic and somatosomatic tangential contacts of Lugaro cells between each other and dendro-dendritic contacts between Lugaro cells and Golgi cells were detected. Total number of Lugaro cells containing NADPH-d in vermis, paramedian lobules, right and left paraflocculus and flocculus equals to 5171. Absence of NO-ergic Lugaro cells in other mammals allows to conclude on the exceptional role of these neurons in rabbit cerebellar cortex.

Animals↗
PubMed1995

[Aspartate aminotransferase of the human cerebellar cortex].

The distribution of aspartate aminotransferase (AST) was studied cytochemically in the cerebellar cortex of the man. Granular cell bodies were labeled, but staining was also found in mossy fibre glomerular synapses. In the molecular and Purkinje cell layers, intensive histochemical reaction was concentrated in the climbing fibres and the "basket" terminal plexus around the Purkinje cells pericaryon. Climbing and mossy fibres formed asymmetric synaptic contacts. Localization of AST in neuronal structures of the human cerebellar cortex suggests to consider these as aspartatergic.

Adolescent↗
PubMed2003

Spreading acidification and depression in the cerebellar cortex.

Optical imaging of activity-dependent pH changes using neutral red has revealed a novel form of propagated activity in the cerebellar cortex: spreading acidification and depression (SAD). Evoked by surface stimulation, SAD is characterized by a propagation geometry that reflects the parasagittal architecture of the cerebellum, high speed of propagation across several folia, and a transient depression of the molecular layer circuitry. The properties of SAD differentiate it from other forms of propagating activity in the nervous system including spreading depression and Ca++ waves. Involving several factors, SAD is hypothesized to be a regenerative process that requires a functioning parallel fibers-Purkinje cell circuit, glutamatergic neurotransmission, and is initiated by increased neuronal excitability. Three possible neuronal and glia substrates in the cerebellar cortex could account for the propagation geometry of SAD. Recently, the authors demonstrated that blocking voltage-gated Kv1.1 potassium channels plays a major role in the generation of SAD. This observation has lead to the hypothesis that the episodic and transient disruption in cerebellar function that characterizes episodic ataxia type 1, a Kv1.1 channelopathy, is due to SAD occurring in the cerebellar cortex.

Acidosis↗
PubMed2004

Phospholipase-C beta1 is predominantely expressed in the granular layer of rat cerebellar cortex.

The beta1 isoform of phospholipase-C is exclusively present in the nucleus of several hematopoietic and non-hematopoietic cell lines and primary cells of different species. When present, it represents the key enzyme for initiating the nuclear phospholipid breakdown that is involved in the cellular response to proliferating and differentiating stimuli. We have studied the expression of this enzyme isoform in the rat cerebellar cortex. We demonstrate that phospholipase-C beta1 (PLCbeta1) is predominantly expressed in the neurons of the granular layer, while it is virtually absent in the molecular and Purkinje cell layers of rat cerebellar cortex. This pattern of expression is partially different from that of the mouse cerebellar cortex, where not only granular cells, but also Purkinje cells express PLCbeta1. The high level of synaptic inputs that converge on granular cells may imply a constantly active nuclear phospholipid metabolism that may not be strictly required for the appropriate cellular responses of the other cell types of rat cerebellar cortex.

Animals↗