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PubMed1987

Parasagittal organization of the rat cerebellar cortex: direct correlation between antigenic Purkinje cell bands revealed by mabQ113 and the organization of the olivocerebellar projection.

The Purkinje cells of the cerebellar cortex and the cortical afferent and efferent projections are organized into parallel parasagittal zones. The parasagittal organization is clearly revealed by immunocytochemistry with a monoclonal antibody, mabQ113. The mabQ113 antigen is confined to a subset of Purkinje cells that are clustered together to form an elaborate, highly reproducible pattern of bands and patches, interspersed with similar mabQ113- regions. The mabQ113+ territories have been classified into seven parasagittal bands (P1+-P7+) in each hemicerebellum. The degree of correspondence between the compartments revealed by the anterograde labeling of the olivocerebellar projection and by mabQ113 immunocytochemistry has been explored in the adult rat. Horseradish peroxide-wheat germ agglutinin conjugate was injected as an anterograde tracer into the inferior olivary complex. When the injection site did not encompass all the olive, an incomplete, patchy labeling of the molecular layer was seen in the cerebellar cortex. Labeled zones of the molecular layer were interrupted by unlabeled regions to give a pattern of parasagittal cortical bands. The positions of these bands were compared with the distribution of the mabQ113+ antigenic bands as seen on the two adjacent sections. Labeled climbing fibers were found to terminate on both mabQ113+ and mabQ113- Purkinje cell zones. The mabQ113+/mabQ113- boundaries and the bands of climbing fibers seen by using the anterograde tracer typically coincide. The one consistent exception is the midline band of mabQ113+ Purkinje cells, P1+. The normal olivocerebellar projection is exclusively contralateral and the climbing fiber projection to the paramedian vermis splits P1+ down the middle, implying that it consists of two adjacent mabQ113+ bands not separated by mabQ113-territory. It is likely that the climbing fiber projection to the cerebellar cortex and the distribution of the two Purkinje cell phenotypes share a common compartmental organization.

Afferent Pathways↗

PubMed1980

[Light and electron microscope study of the cerebellar cortex in the cow, sheep and goat].

In order to investigate the fine structure of the cerebellar cortex of domestic ruminants, tissue specimen were taken of the Lingula, Declive, Nodulus, Lobus paramedianus and Flocculus of 30 cows, sheep, and goats. The following techniques were used: Luxol-Fast-Blue and Nisslstaining, Bodian and Golgi impregnation according to BUBENAITE and to KEMALI (1976). Electronenmicroscopically, differences between these species were seen only in the thickness of the three layers and in the size and topography of the 7 different cells and the fibres of the cerebellar cortex. In contrast to other species, soma and fibres of the Purkinjecells often contained numerous lamellar bodies. As in other animals the granular endoplasmic reticulum is arranged in form of nuclear caps.

Animals↗

PubMed1982

Influence of altered thyroid and nutritional states on early histogenesis of the rat cerebellar cortex with special reference to synaptogenesis.

On day of birth, the synaptic density of the rat cerebellar cortex in experimental, as compared to control, rats was slightly reduced or increased, respectively, after propylthiouracil treatment of the dam or thyroxine injection of the fetus. The stimulation of synaptogenesis in thyroxine-treated neonates was particularly obvious at the level of the ganglionic layer containing Purkinje cell bodies and was accompanied at the same level by accelerated growth of the presynaptic endings and perisomatic processes of the Purkinje cells. Undernourishment of the dam from day 6 of gestation led to an unexpected stimulation of synaptogenesis in the cerebellar cortex of the neonates; synaptic density was significantly increased above the normal value and much more markedly than in the thyroxine-treated neonates, but there was no abnormal proliferation of the neuronal processes. Different mechanisms underlay the transient stimulation of synaptogenesis in these two conditions. These results have been related to the disturbances in the development of Bergmann glia previously found soon after birth in altered thyroid and nutritional states.

Animal Nutritional Physiological Phenomena↗

PubMed2002

Roles of inhibitory interneurons in the cerebellar cortex.

The roles of inhibitory interneurons in the cerebellar cortex were investigated. First, Golgi cells were specifically eliminated in transgenic mice in which Golgi cells expressed human interleukin-2 receptor alpha subunit (IL2Ralpha). Injection of exotoxin coupled to anti-IL2Ralpha antibody in the cerebellum of the transgenic mouse eliminated Golgi cells and abolished GABA and synaptic inhibition in the granular layer. After elimination of Golgi cells, acute severe ataxia and subsequent mild motor discoordination were observed. In the latter chronic phase, NMDA receptor-mediated synaptic response was reduced in granule cells. Our findings indicate that elimination of GABAergic inhibition in the granular layer caused overexcitation of granule cells resulting in severe ataxia, and then NMDA receptors in granule cells were downregulated, compensating for the reduction of GABAergic inhibition and improving motor control. In the second part, we report on the regulation mechanism of synaptic plasticity at inhibitory synapses on Purkinje cells (PCs). Inhibitory synaptic transmission on a PC is potentiated after repetitive PC depolarization. This synaptic plasticity (rebound potentiation, RP) was suppressed when a presynaptic neuron was activated during the PC depolarization. This synaptic regulation is unique in the sense that the homosynaptic activity suppresses the induction of synaptic plasticity. The mechanism of how presynaptic activity suppresses RP was examined. GABA released from the presynaptic terminal activated not only GABA(A) receptor but also GABA(B) receptor. The latter was coupled to Gi/o proteins, which downregulated adenylyl cyclase reducing cAMP and inactivated cAMP-dependent protein kinase (PKA). Downregulation of PKA suppressed RP induction.

Animals↗

PubMed1994

Glutamate-immunoreactive climbing fibres in the cerebellar cortex of the rat.

The climbing fibre system, one of the two main excitatory inputs to the cerebellar cortex, is anatomically and physiologically well characterized, while the nature of its neurotransmitter is still a matter of debate. We wished to determine whether glutamate-immunoreactive profiles with the morphological characteristics of climbing fibres could be found in the rat cerebellar cortex. For this purpose, a monoclonal 'anti-glutamate' antibody has been used in combination with a sensitive postembedding immunoperoxidase method on semi-thin sections or in combination with a postembedding immunogold method on ultrathin sections. At the light microscopic level, climbing fibres appeared as strongly stained fibrous profiles, chains of interconnected varicosities or heavily labelled dots of various sizes, often in close apposition to principal Purkinje cell dendrites. At the electron microscopic level, certain labelled varicosities or more elongated profiles resembling climbing fibre terminals were in synaptic contact with dendritic spines of Purkinje cells. Quantitative analysis of gold particle densities showed that such elements were about three to four times more heavily labelled than their postsynaptic partners. The results obtained in this study demonstrate that at least a subset of climbing fibres and their terminals contain relatively high levels of glutamate-like immunoreactivity and provide additional evidence for a role of glutamate as transmitter in these cerebellar afferents.

Animals↗

PubMed2003

Unraveling the cerebellar cortex: cytology and cellular physiology of large-sized interneurons in the granular layer.

Neuronal network behaviors emerge from complex interactions between excitatory relay cells, principal cells and inhibitory interneurons. Therefore, characterizing homogeneous cell types and their properties is an essential step towards understanding information processing in the brain. The cerebellar cortex is generally described as a repetitive circuit composed of only five cell types. However, recent studies have revealed an unexpected diversity in the morphological, neurochemical and electrophysiological properties of the large-sized granular layer interneurons. These data are reviewed here with an emphasis on the synaptic interactions of the different cell types within the cerebellar cortex. The existence of a complex network of excitatory and inhibitory interneurons controlling the spatial and temporal pattern of granule cell firing is documented, providing insights into the cellular and synaptic processes underlying oscillations and synchronization in the cerebellar cortex.

Animals↗

PubMed1988

[Synapses with a different synaptic contact structure in the cerebellar cortex].

The ultrastructure of cerebellar axosomatic (inhibitory) and axo-dendritic (excitatory) synapses were studied on the Purkinje cells and in the lower molecular layer of guinea-pigs and rats, respectively. It was shown that synaptic contacts of excitatory and inhibitory synapses differed in the existence of desmosome-like structures near the active zones. The classification of synaptic functions according to the ultrastructure of specialized contacts, earlier developed to identify neurons of lower vertebrates, is supposed to be applicable to the nervous system of higher vertebrates.

Animals↗

PubMed1993

Elevated stimulatory and reduced inhibitory G protein alpha subunits in cerebellar cortex of patients with dominantly inherited olivopontocerebellar atrophy.

Although guanine nucleotide binding proteins (G proteins) are one of the critical components of signal transduction units for various membrane receptor-mediated responses, little information is available regarding their status in brain of patients with neurodegenerative illnesses. We measured the immunoreactivity of G protein subunits (Gs alpha, Gi alpha, Go alpha, Gq/11 alpha, and G beta) in autopsied cerebellar and cerebral cortices of 10 end-stage patients with dominantly inherited olivopontocerebellar atrophy (OPCA) who all had severe loss of Purkinje cell neurons and climbing fiber afferents in cerebellar cortex. Compared with the controls, the long-form Gs alpha (52-kDa species) immunoreactivity was significantly elevated by 52% (p < 0.01) in the cerebellar cortex of the OPCA patients, whereas the Gi1 alpha concentration was reduced by 35% (p < 0.02). No statistically significant differences were observed for Go alpha, Gi2 alpha, G beta 1, G beta 2, or Gq/11 alpha in cerebellar cortex or for any G protein subunit in the two examined cerebral cortical subdivisions (frontal and occipital). The cerebellar Gs alpha elevation could represent a compensatory response (e.g., sprouting, reactive synaptogenesis) by the remaining cerebellar neurons (granule cells?) to neuronal damage but also might contribute to the degenerative process, as suggested by the ability of Gs alpha, in some experimental preparations, to promote calcium flux. Further studies will be required to determine the actual functional consequences of the G protein changes in OPCA and whether the elevated Gs alpha is specific to OPCA cerebellum, because of its unique cellular pattern of morphological damage, or is found in brain of patients with other progressive neurodegenerative disorders.

Adult↗

PubMed1987

Cardiovascular and respiratory responses evoked from the posterior cerebellar cortex and fastigial nucleus in the cat.

1. In both anaesthetized and decerebrate cats the cerebellar cortex (lobules VI, VII, VIII, IX and X) and the fastigial nucleus (f.n.) have been stimulated electrically, and chemically, while recording changes in phrenic nerve discharge, heart rate, arterial blood pressure and renal and femoral blood flow. 2. Stimulation of lobules VI, VII, VIII and Xb failed to elicit any cardiovascular or respiratory changes. Activation of lobule IX (the uvula), and in some preparations sub-lobule Xa, evoked cardiovascular and respiratory responses consistently. In the anaesthetized cat, electrical stimulation of the uvula evoked apnoea, a small bradycardia and a depressor response associated with vasodilatation in the hindlimb vascular bed. In contrast, stimulation in an equivalent region in a decerebrate preparation elicited an apneustic discharge, a pronounced tachycardia and a rise in arterial pressure with vasoconstriction in both renal and femoral vascular beds. In both the anaesthetized and decerebrate animals the pattern of response elicited by chemical activation was identical to that seen with electrical stimulation. 3. Electrical, or chemical, stimulation after administration of anaesthetic to the decerebrate cat then evoked an identical pattern of response to that seen in the 'intact' anaesthetized animal. This evidence suggests that the reversal in the pattern of the response in an effect of the anaesthetic agent and not the decerebration itself. 4. The only area of the f.n. to produce cardiovascular effects was the rostral region. Electrical stimulation of the rostral f.n. in both anaesthetized and decerebrate preparations inhibited central inspiratory activity and evoked tachycardia, along with a pressor response associated with vasoconstriction in both renal and femoral vascular beds. In contrast, chemical excitation of those sites in the rostral f.n. shown previously to produce pronounced cardiovascular and respiratory changes failed to elicit any changes in the recorded variables. 5. The present evidence suggests that there are two areas in the cat cerebellum which can exert pronounced cardiovascular and respiratory effects. The patterns of response elicited by electrical stimulation of the posterior cortex and rostral f.n. are mediated by two separate cerebellar-brainstem pathways as judged by the two different effects of anaesthesia on the evoked responses. We suggest that the f.n. may not play a role in the control of the cardiovascular system since chemical excitation of cell bodies of the rostral f.n. failed to elicit the so-called 'fastigial pressor response'.

Anesthesia, General↗

PubMed1975

Fine structure of labelled axons in the cerebellar cortex and nuclei of rodents and primates after intraventricular infusions with tritiated serotonin.

The cerebellar cortex and deep cerebellar nuclei in rats and rhesus monkey were studied after treatment with monoamine oxidase inhibitor and continuous intraventricular infusion with 10(-5) M serotonin-3H. Autoradiographs were prepared for light and electron microscopy. The cerebellum contained no labelled cells. Labelled unmyelinated axons arrive from the brain stem via the periventricular zones of the aqueduct and fourth ventricle. In the parafloccular cortex about 1 per cent of the mossy fibers are labelled, together with a small number of fine varicose axons in the molecular layer that run parallel to the folial axes (less than 0.1%). In the paravermal and vermal cortex there are few labelled fibers in the granular layer and a five-fold greater number of labelled axons in the molecular layer (about 0.5%). Apparently three systems of serotonin-containing axons are present in the cortex: mossy fibers, parallel fiber-like, and a diffuse system in granular and molecular layers. The fastigial (medial), interpositus, and dentate (lateral) nuclei, lateral vestibular and other vestibular nuclei all have numerous labelled axons. The dentate and interpositus nuclei receive labelled fibers which arrive through the superior cerebellar peduncle as well as from the periventricular area. Six morphologically different classes of labelled axon terminals have been differentiated. Class 1a, the mossy fiber rosettes, and class 1b, the CAT2 axons, have small, round, clear synaptic vesicles and large granular vesicles (lgv); class 2 axons have a distinctive collection of round granular vesicles; class 3 boutons have numerous tubular profiles, a few containing dense dots, packed in a dark axoplasmic matrix; class 4 axons have tiny 250 A granular vesicles, clear tubular profiles and occasional LGV; class 5 terminals have numerous LGV, both round and elongated, with clear round and tubular profiles; class 6 terminals have LGV, clear and granular synaptic vesicles and clear tubular profiles. All these axons have LGV 900 A in diameter with 500-600 A variably dense centers that do not fill the vesicle, and Gray's type 1 axodendritic or axasomatic synapses on postsynaptic locations in the cortex and nuclei. Labelled axons in the cortex end as mossy fibers upon granule cell dendrites in glomeruli (Class 1a) or upon dendrites of cortical interneurons, e.g. Golgi cells, basket and stellate cells, and not on Purkinje cells. ...

Animals↗

PubMed1987

The fine structure of the node of Ranvier in the rat cerebellar cortex.

The transitional zone between the myelinated and the terminal portions of nerve fibers was electron microscopically investigated in the cerebellar cortex of normal rats. A noteworthy finding in the present study is the existence of a "heminode" consisting of the myelinated and non-myelinated portions, as demonstrated within a single section. The heminode seems to be a characteristic structure in the granular layer of the rat cerebellar cortex.

Animals↗

PubMed1999

Novel form of spreading acidification and depression in the cerebellar cortex demonstrated by neutral red optical imaging.

A novel form of spreading acidification and depression in the rat cerebellar cortex was imaged in vivo using the pH-sensitive dye, Neutral red. Surface stimulation evoked an initial beam of increased fluorescence (i.e., decreased pH) that spread rostrally and caudally across the folium and into neighboring folia. A transient but marked suppression in the excitability of the parallel fiber-Purkinje cell circuitry accompanied the spread. Characteristics differentiating this phenomenon from the spreading depression of Leao include: high speed of propagation on the surface (average of 450 microm/s), stable extracellular DC potential, no change in blood vessel diameter, and repeatability at short intervals. This propagating acidification constitutes a previously unknown class of neuronal processing in the cerebellar cortex.

Acids↗

PubMed1998

Modification of activity-dependent increases of cerebral blood flow by excitatory synaptic activity and spikes in rat cerebellar cortex.

1. Mechanisms of activity-dependent increases in cerebral blood flow (CBF) were examined in rat cerebellar cortex using the laser Doppler flow technique and extracellular recordings of single unit activity and field potentials. 2. Stimulation of the monosynaptic climbing fibre system evoked long-lasting complex spikes in Purkinje cells, and extracellular field potentials with a characteristic profile that indicated contributions from both passive and active membrane mechanisms. The concomitant CBF increases were reproducible at fairly short intervals, and suggest that both synaptic activity and spikes may contribute to increased CBF. 3. Stimulation of the disynaptic parallel fibre system inhibited the spiking activity in Purkinje cells, while the postsynaptic activity increased as indicated by the simultaneously recorded field potential. Nevertheless, CBF always increased. The inhibition of spike firing activity was partly dependent on GABAergic transmission, but may also relate to the intrinsic membrane properties of Purkinje cells. 4. The CBF increases evoked by parallel or climbing fibre stimulation were highly correlated to the sum of neural activities, i.e. the negativity of field potentials multiplied by the stimulus frequency. This suggests a robust link between extracellular current flow and activity-dependent increases in CBF. 5. AMPA receptor blockade attenuated CBF increases and field potential amplitudes, while NMDA receptor antagonism did not. This is consistent with the idea that the CBF responses are of neuronal origin. 6. This study has shown that activity-dependent CBF increases evoked by stimulation of cerebellar parallel fibres are dependent on synaptic excitation, including excitation of inhibitory interneurones, whereas the net activity of Purkinje cells, the principal neurones of the cerebellar cortex, is unimportant for the vascular response. For the climbing fibre system, not only synaptic activity but also the generation of complex spikes from Purkinje cells contribute to the increases in CBF. The strong correlation between CBF and field potential amplitudes suggests that extracellular ion fluxes contribute to the coupling of brain activity to blood flow.

Animals↗

PubMed1975

Cell number and cell density in the cerebellar cortex of man and some other mammals.

The number of cells per unit volume was determined in the cerebellar cortex of man and 19 other mammals. The cell density (i.e. the number of cells per unit volume) decreases from mammals with a low brain weight to those with a higher brain weight. This decrease in the number of cells is found to be proportional for all three layers of the cerebellar cortex. In addition, the ratio of Purkinje cells to granule cells was determined. In contrast to the decrease of all cell types with increasing brain weight, this ratio varies remarkably among the mammals and is not correlated with brain weight. In man, this ratio is 1:2991, while it is lower in all other mammals investigated. These differences in the ratio of Purkinje cells to granule cells and the decrease in cell density with increasing brain weight are discussed in relation to brain evolution.

Animals↗

PubMedDate not supplied

[The effect of restoring adequate nutrition on the relation between nerve and glial cells in the cerebellar cortex of malnourished mice].

Changes in the distribution density of neurons and gliocytes of the ganglionic layer of the cerebellar cortex in mice were studied during malnutrition and further alimentary rehabilitation. The results obtained have evidenced that the distribution density of neurons is increased, while that of gliocytes is decreased in the ganglionic layer of the cerebellar cortex of mice which received a low-protein diet from the 10th to the 40th day of life. These changes were partially recovered after alimentary rehabilitation, while alimentary rehabilitation combined with drug correction (addition of carnitine) leads to the complete recovery of the cerebellum histological structure.

Animals↗

PubMed1978

Focal brain hyperthermia. I. The cerebellar cortex.

Focal brain hyperthermic methodology has been described and data presented on the cerebellum which show that enhancement of electrical activity of cerebellar cortex occurs when this method is used with careful monitoring of temperature. The duration of electrically induced cerebral after-discharges is shortened when cerebellar warming reaches 39.5--42.0 degrees C,. Since these effects are repeatable over many hours, there appears to be little, if any, resultant damage. Such induced changes in the cerebrum resemble those previously reported in which electrical stimuli were applied to the cerebellar cortex.

Animals↗

PubMed1974

The projection of the posterior knee joint nerve to the cerebellar cortex.

1. In decerebrate cats, electrical stimulation of the posterior knee joint nerve evokes in the depth of the cerebellar cortex field potentials which have been identified as due to both mossy and climbing fibre inputs.2. The potentials evoked through the mossy fibres have a latency of 15-17 msec and are more widespread. Those evoked through the climbing fibres have a latency of 26-33 msec and are more restricted.3. Stimulation of the larger fibres originating from the Golgi receptors gives only a very restricted projection. When the fibres originating from the Ruffini receptors are also activated, the effect on the cerebellar cortex is more widespread.4. The results have been confirmed by recording unitary activity.

Animals↗

PubMed1997

Transient expression of FGF-5 mRNA in the rat cerebellar cortex during post-natal development.

Previously, we showed that fibroblast growth factor (FGF) receptor-4 mRNA was transiently expressed in proliferative granule cells of the external granule layer of the rat cerebellar cortex during early post-natal development (A. Miyake et al., Mol. Brain Res., 31 (1995) 95-100). In this study, we examined the expression of FGF-5 mRNA in the rat brain during post-natal development by in situ hybridization. FGF-5 mRNA was transiently expressed in granule cells of the internal granule layer of the cerebellar cortex during early post-natal development. The temporal sequence of FGF-5 mRNA expression was similar to that of FGFR-4 mRNA expression. As the proliferation of granule cells in the external granule layer and their migration through the molecular layer into the internal granule layer actively occur during these periods, the present findings suggest that FGF-5 as well as FGFR-4 might play important roles in the proliferation and/or migration of granule cells during the post-natal development of the cerebellar cortex.

Animals↗