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Biomedical subjects

J Mariani

Publications and source records attributed to J Mariani.

At least 109 records · Page 6Linked to original sources

Stability of inferior olivary neurons in rodents. I. Moderate cell loss in adult Purkinje cell degeneration mutant mouse.

A light microscopic study and cell counts of the inferior olivary nucleus (ION) were performed in the Purkinje cell degeneration mutant mouse (pcd/pcd). Six groups of animals aged from 24 to 210 days were studied and compared to age matched (+/+) C57Bl.6J mice. A cell deficit of about 30% was found in the youngest animals studied; it did not change significantly with age. The deficit affects the 4 subnuclei of the ION, but predominates clearly in the medial accessory olive. This cell loss is already established at the moment when the massive loss of Purkinje cells that has been reported in this mutant occurs. Thus it is not yet known if the ION represents a primary site of gene action or if the deficit is secondary to another cellular event, presumably the loss of Purkinje cells.

Aging↗

Neuronal death and synapse elimination in the olivocerebellar system: III. Cell counts in the inferior olive of developing rats X-irradiated from birth.

The change with age of cell number in the developing inferior olivary nucleus (ION) of the normal rat, compared to the time course of the regression of the polyneuronal innervation of Purkinje cells by olivary axons (i.e., the climbing fibers), suggests that the involution of the redundant olivocerebellar contacts is caused by a reduction of axonal branching rather than by degeneration of the parent cells, this being also suggested by the normal size of the olivary population in adult rodents whose Purkinje cells retain polyneuronal innervation. However, the similar size of the adult ION population does not necessarily imply that the development history is the same in normal and multiply innervated adult rodents. Therefore, cell counts were performed in developing rats which had been repeatedly X-irradiated from birth until postnatal day 14 and which retained polyneuronal innervation. The results show that, although less marked than during normal development, the evolution of the ION population is also characterized by a phase of cell loss followed by a slow increase. However, the number of cells in X-irradiated rats is higher than in their controls from birth to postnatal day 15 but becomes identical at 20 days and later. These data confirm that cell death in the ION does not play a major role in the shaping of olivocerebellar connections.

Aging↗

Peripheral maps and synapse elimination in the cerebellum of the rat. I. Representation of peripheral inputs through the climbing fiber pathway in the posterior vermis of the normal adult rat.

The present study gives a detailed description of the functional characteristics and of the topographic distribution of responses, mediated through the climbing fiber pathway and elicited by electrical stimulation of several peripheral inputs, in a circumscribed region of the posterior vermis of the rat cerebellum. Experiments were carried out on normal adult rats under urethane anaesthesia. Purkinje cells (PCs) which responded to the electric stimulation of the contralateral snout, of the ipsilateral and contralateral hindlimb or forepad, and of the tail were recorded in an area extending 1000 microns laterally to the midline in the vermal part of lobules VII and VIII. Using precise micromapping techniques and computer analysis, we located the cells on the map of the unfolded PC layer. Taking into account the mean latency of the responses and the probability of discharge of the PCs, restricted areas of projection were found for the snout, the forepads and the tail. Zones of short-latency responses form compact patches of less than 1 mm2. There was some overlap of projection zones from tail and snout and from forepads and snout. In these zones, there was a convergence of several peripheral inputs on some of the PCs tested. No precise projection of the hindlimbs could be detected in the same lobules. These results fit well with the hypothesis already proposed that the representation of peripheral inputs through the climbing fiber pathway is fractured into a mosaic of patches, which are partly overlapping, and in which remote parts of the body are represented in adjacent areas.

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Peripheral maps and synapse elimination in the cerebellum of the rat. II. Representation of peripheral inputs through the climbing fiber pathway in the posterior vermis of X-irradiated adult rats.

The present study gives a detailed description of the functional characteristics and of the topographic distribution of responses mediated through the climbing fiber (CF) pathway in the cerebellum of adult rats which have been repeatedly irradiated from birth so that the Purkinje cells (PCs) in the adult remained innervated by several climbing fibers instead of one. Experiments were carried out under urethane anaesthesia. After electrical stimulation of the contralateral snout, the ipsilateral and contralateral hindlimb or forepad, and the tail, CF-EPSPs were recorded from PCs in an area extending 1000 microns laterally to the midline in the vermal part of lobules VII and VIII. The stepwise variation of CF-EPSP amplitude demonstrated the multiple innervation of the PCs by CFs in these animals. The responses of a given PC through separate CFs were analyzed separately and, using precise micromapping techniques and computer analysis, cells were located on the map of the unfolded PC layer. Taking into account the mean latency of the responses and the probability of discharge of the PCs, restricted areas of projection were found for the snout, the forepads and the tail. Zones of short-latency responses formed compact patches of approximately 1 mm2. Their disposition was very similar to that found in normal rats. The responses evoked through the different CFs converging on a given PC were in general very homogeneous and very similar to those recorded in control rats. There was some overlap of projection zones from tail and snout and from forepads and snout. In this latter case, there was a convergence of several peripheral inputs on some of the PCs tested. No precise projection of the hindlimbs could be detected in the same lobules. These results suggest that, with the type of stimulation used, the representation of peripheral inputs through CF pathway is roughly conserved even though multiple innervation of PCs by CFs is maintained until adulthood.

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Evidence for a multiple innervation of cerebellar Purkinje cells by climbing fibers in adult ferrets infected at birth by a mink enteritis virus.

Newborn ferrets were inoculated with Mink Enteritis virus (parvovirus). They developed a cerebellar hypoplasia and presented severe ataxia. Electrophysiological study by intracellular recordings in the cerebellar cortex demonstrates that in these ferrets, like in other mammals, Purkinje cells deprived from granule cell input during development remain multiply innervated by climbing fibers in the adult.

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Decreased number of cells in the inferior olivary nucleus of the adult mouse (+/sg) heterozygous for the staggerer gene.

Light microscopic study and cell counts of the inferior olivary nucleus were performed in adult mouse (+/sg), i.e. heterozygous for the staggerer gene. Two, six, and twelve-month-old animals were studied and compared to (+/+) C57BL6J mice of the same age. The number of cells and their repartition within the four subnuclei of the inferior olivary nucleus were normal in 2-month-old (+/sg) mice but a cell loss appears afterwards and mostly between 6 and 12 months so that about 30% of the olivary cells are missing in (+/sg) mice aged 12 months. The deficit affects the four inferior olivary nucleus subnuclei but predominates in the dorsal accessory olive. This cell loss is the first described expression of the mutation in the (+/sg) mouse, and it is not yet known if the inferior olivary nucleus represents a primary site of gene action or if the deficit is secondary to a hitherto unnoticed abnormality in the heterozygous (+/sg) mouse.

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28 K cholecalcin (CaBP) levels in abnormal cerebella: studies on mutant mice and harmaline- and 3-acetylpyridine-treated rats.

The cerebellar Purkinje cells of both birds and mammals contain a specific calcium-binding protein, 28 K cholecalcin (CaBP). This is the same protein as the vitamin D-dependent kidney CaBP, but its Purkinje cell level is apparently vitamin D independent. The cerebellar CaBP contents of 3-acetylpyridine- and harmaline-treated rats and 5 mutant mouse strains (Purkinje cell degeneration, reeler, weaver, staggerer and nervous) were measured using a specific radioimmunoassay. The results indicate that the level of cerebellar CaBP is not dependent on the physiological state of the Purkinje cells but is an intrinsic measure of the size of the Purkinje cell population.

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Neuronal death and synapse elimination in the olivocerebellar system. I. Cell counts in the inferior olive of developing rats.

A transient multiple innervation of cerebellar Purkinje cells by climbing fibers has been described during postnatal development of the rat. The aim of the present study was to determine if the regression of redundant synapses is related to the loss of presynaptic cells in the inferior olivary nucleus (ION), which is the sole source of climbing fibers in rodents. To this end, the population size of the ION was evaluated by counting healthy cells of the four main subnuclei in rats from birth to adulthood. The cell population at birth was found to be very similar to that of the adult animal (27,655 versus 28,385), but a loss of 25% of the cells occurred in the first five days, presumably through their death since degenerating cells were observed over the same period. Although cell loss was found throughout the whole nucleus, it was more pronounced in the medial accessory olive. A subsequent apparent increase of the cell population was observed so that the adult value was again reached at 15 days. The evolution of the ION population is then characterized by a period of moderate cell death which takes place before the peak of polyneuronal innervation of Purkinje cells by olivary axons is attained. This strongly suggests that the removal of the redundant synaptic contacts established by climbing fibers onto Purkinje cells during development is caused by a progressive reduction of the branching of olivary axons rather than by degeneration of the presynaptic cells.

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Neuronal death and synapse elimination in the olivocerebellar system. II. Cell counts in the inferior olive of adult x-irradiated rats and weaver and reeler mutant mice.

Cell death in the developing rat inferior olive precedes the regression of the polyneuronal innervation of Purkinje cells by olivary axons (i.e., climbing fibers), suggesting that the involution of the redundant olivocerebellar contacts is caused by a withdrawal of supernumerary axonal collaterals rather than by degeneration of the parent cell. However, a subsequent apparent increase of the olivary population occurs, which could eventually mask a residual presynaptic cell death taking place at the same time. Therefore, cell counts were performed in the inferior olive of adult rodents in which the multiple innervation of Purkinje cells by olivary axons is maintained, with the idea that if cell death plays a role in the regression of supernumerary climbing fibers, the number of olivary cells should be higher in these animals than in their controls. The results show that the size of the cell population in the inferior olive of weaver and reeler mutant mice and rats degranulated by early postnatal x-irradiation does not differ significantly from that of their controls. Similarly, the distribution of the cells in the four main olivary subnuclei is not modified in weaver mice and x-irradiated rats. The present data further support the assumption that the regression of the polyneuronal innervation of Purkinje cells occurs independently of cell death in the presynaptic population.

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Decreased number of cells in the inferior olivary nucleus of the developing staggerer mouse.

Light-microscopic study and cell counts of the inferior olivary nucleus (ION) were performed in staggerer mutant mice and compared to those obtained in C57B16J controls. The main result is that 60% of the olivary cells are missing in 24-day-old mutants and that most of the deficit is already present on postnatal day 10. It has been previously shown that the staggerer gene exerts an intrinsic effect on the Purkinje cells. Whether cells of the inferior olive are, in addition to Purkinje cells, a primary site of gene action, or whether they are retrogradely affected by the cerebellar malformation, remains unknown from the present study.

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[Existence of very weak level of residual multiple innervation of Purkinje cells through climbing fibers in the cerebellum of the normal adult rat].

Extra- or intracellular unit responses of Purkinje cells to the activation of climbing fibres were recorded in the cerebellum of adult rats. Out of 1.719 cels studied, only 4 were found to be innervated by more than one climbing fibre. This very small rate of residual multiple innervation in the normal adult illustrates the accuracy of the synaptic elimination process which leads to the innervation of each Purkinje cell through only one climbing fibre during normal development in the rat.

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Stability of multiple innervation of Purkinje cells by climbing fibers in the agranular cerebellum of old rats X-irradiated at birth.

In the cerebellum of old X-irradiated rats, the multiple innervation of Purkinje cells by climbing fibers, which normally regresses after birth, was still present up to 18 months. Furthermore, the mean number of synaptic contacts upon each Purkinje cell was not smaller than what is observed in young adults, indicating that, after irradiation, these redundant synapses are definitively stabilized.

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Extent of multiple innervation of Purkinje cells by climbing fibers in the olivocerebellar system of weaver, reeler, and staggerer mutant mice.

Multiple innervation of cerebellar Purkinje cells (PCs) by climbing fibers (CFs) has been described recently in adult weaver, reeler, and staggerer mutant mice, instead of the monoinnervation found in normal adults. In the present study, the extent of this multiple innervation was estimated by two methods, using both evoked and spontaneous activity of the olivocerebellar system. Concordant values were obtained: the mean number of CF collaterals per PC was between 3.5 and 4 in weaver and staggerer and close to 3.2 for the multiply innervated PCs of reeler mice. These values are of the same order of magnitude as those for the transient multiple innervation in developing rats (Mariani and Changeux, 1981a,b).

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Effect of 1-methyl cyclohexane carboxylic acid on electrical activity of Purkinje cells in the rat: evidence for a potentiation of intracerebellar inhibition.

The effect of an anticonvulsant compound (Simiand, Ferrandes, Lacolle and Eymard, 1979), 1-methyl cyclohexane carboxylic acid (CCA), upon the electrical activity of Purkinje cells (PCs) was studied in the cerebellar cortex of the rat in vivo. Cyclohexane carboxylic acid (200-400 mg/kg i.v.) decreased the spontaneous simple spike (SS) activity of the Purkinje cells tested without modifying the complex spike (CS) frequency. Two effects of CCA upon intracortical inhibition were observed: (1) the decrease in firing rate that followed surface stimulation of the parallel fibres (LOC stimulation) was enhanced after injection of CCA; (2) the depression of the antidromic field potential of Purkinje cells by a conditioning stimulation was also enhanced after injection of CCA. This latter effect was suppressed in a reversible manner by injection of bicuculline. These results strongly suggest that the effect of CCA upon electrical activity of Purkinje cells is related to an enhancement of the inhibition exerted on Purkinje cells by GABAergic, cerebellar interneurones. The possible mechanisms of action of CCA are discussed.

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Ontogenesis of olivocerebellar relationships. I. Studies by intracellular recordings of the multiple innervation of Purkinje cells by climbing fibers in the developing rat cerebellum.

The establishment of the adult innervation of Purkinje cells (PCs) by climbing fibers (CFs) was studied in the cerebellar vermis of the developing rat. Excitatory postsynaptic potentials (EPSPs) evoked in PCs by activation of the climbing fibers (CF-EPSPs) were recorded intracellularly from a total of 310 cells in young rats aged from 3 to 15 postnatal days. The CF system was activated by electrical stimulation of either the inferior olive (IO) nucleus or the region near the fastigial nucleus (juxtafastigial or JF stimulation). A given PC at each age was considered to be innervated by more than one CF when the amplitude of the spontaneous or evoked CF-EPSPs fluctuated in a stepwise manner. On the other hand, innervation of a PC by a single CF was established on the basis of the all-or-none character of CF-EPSPs. Two parameters were followed throughout development, the percentage of multiply innervated PCs and the mean number of steps in the evoked CF-EPSPs. The data presented confirm the transient multiple innervation of PCs by CFS on postnatal days 8 and 9 (Crépel, F., J. Mariani, and N. Delhaye-Bouchaud (1976) J. Neurobiol. 7: 567-578) and strongly suggest its existence at earlier stages (from postnatal day 3). Moreover, it is shown that the multiple innervation was maximal on postnatal day 5 and then decreased until the innervation by a single CF was established on day 15.

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Ontogenesis of olivocerebellar relationships. II. Spontaneous activity of inferior olivary neurons and climbing fibermediated activity of cerebellar Purkinje cells in developing rats.

During development of vertebrate cerebellum, a multiple innervation of each Purkinje cell (PC) by several climbing fibers (CFs) (Crépel, F., J. Mariani, and N. Delhaye-Bouchaud (1976) J. Neurobiol. 7: 567-578; Mariani, J., and J. -P. Changeux (1981) J. Neurosci. 1: 696-702) precedes the one-to-one relationship characteristic of the adult stage. In the present study, the spontaneous activity of inferior olivary neurons (whose axons constitute the CFs) and the spontaneous activity elicited in PCs by the CF system were investigated in developing rats. Extracellular unitary recordings were obtained in medial and dorsal accessory olives from 249 neurons from 1-day-old to adult animals. The mean discharge rate varied from 0.19 spike . sec-1 on day 1 to 1.69 spikes . sec-1 on postnatal day 21 and 1.78 spikes . sec-1 in adult animals. Although the spontaneous discharge was low, interspike interval histograms were constructed for a sample of cells. Their modal value varied from a mean value of 660 msec on day 1 to 250 msec in the adult with, however, marked variations at each age in the young animals. Intracellular recordings from PCs were performed in rats ranging in age from 5 to 15 postnatal days. The spontaneous (i.e., asynchronous) discharge of excitatory postsynaptic potentials mediated neurons at the same age. The main results are the following: (1) In PCs innervated by one CF, the mean frequency of CF-EPSPs was similar to the discharge of inferior olivary neurons; (2) in PCs innervated by several CFs, the mean discharge of CF-EPSPs was much higher than the discharge of inferior olivary neurons; (3) as a whole, the CF-mediated activity of PCs decreased from day 5 to day 11, while the multiple innervation disappeared; from then on, the activity increased with the maturation of inferior olivary neurons until adult values. The ratio of the frequencies of CF-EPSPs and olivary neurons discharges gives an approximate mean number of CF collaterals per PC at each age; it varied from 3.6 on day 5 to values close to 1 on day 11 and the following days.

Action Potentials↗

[Intracellular recordings of the multiple innervation of Purkinje cells by climbing fibers in the cerebellum of the developing rat].

Intracellular recordings of postsynaptic potentials evoked in cerebellar Purkinje cells (PCs) by activation of the climbing fibers (CFs) have been obtained from 3 to 15 day-old Rats. The data presented confirm the multiple innervation of PCs by CFs on postnatal days 8-9, and demonstrate its existence at earlier stage (from day 3). The evolution of the precentage of multinnervated PCs and of the mean number of CFs collaterals per PC was followed until the monoinnervation was established on day 15.

Aging↗