Biomedical subjects

P Strata

Publications and source records attributed to P Strata.

At least 19 recordsLinked to original sources

PubMed1999

Control of spine formation by electrical activity in the adult rat cerebellum.

Dendritic spines are a key structure in neuronal plasticity. Enhanced activity is commonly associated with an increase in spine size and density. Purkinje cell dendrites are characterized by a proximal and a distal compartment on which climbing fibers and parallel fibers, respectively, impinge. The proximal region has a very low spine density, whereas the distal region has a high density. Previous experiments showed that after climbing fiber deletion, Purkinje cells become hyperactive, and a large number of spines develop on the proximal dendrites. Here we show that the same hyperspiny transformation occurs in the proximal dendrites of adult Purkinje cells by depressing electrical activity with tetrodotoxin. Thus, spines in different dendritic compartments are created or maintained independently from the level of Purkinje cell-firing rate and when the afferent activity is blocked. This conclusion supports the view that spinogenesis is the expression of an intrinsic program and the two regions of the dendritic tree respond differently to activity block because of differences in the inputs that they receive. On tetrodotoxin treatment, climbing fibers become atrophic and may sprout thin collateral ramifications directed mainly toward the granular layer. All changes are reversible on tetrodotoxin removal. Therefore, Purkinje cells provide a model where spines in different compartments of the same neuron are differently regulated by the activity of their local afferents. In addition, electrical activity is also essential to maintain the full climbing fiber innervation.

Animals↗

PubMed1998

Retrograde regulation of growth-associated gene expression in adult rat Purkinje cells by myelin-associated neurite growth inhibitory proteins.

Axon regeneration requires that injured neurons reinitiate long-distance growth and upregulate specific genes. To address the question of whether inhibitory environmental cues along the axon could exert a negative, tonic downregulation of growth-associated genes, we have examined adult rat Purkinje cells, which are endowed with poor regenerative capabilities. First we have compared their response to axotomy with that of neurons of the inferior olive, lateral reticular nucleus, and deep cerebellar nuclei, all of which vigorously regenerate into growth-permissive transplants. These injured neurons upregulate the transcription factors c-Jun and JunD, GAP-43, and NADPH diaphorase. In contrast, most axotomized Purkinje cells fail to express any of these markers, showing that the strength of this response parallels the regenerative potential of the examined neuron populations. However, strong upregulation of the same genes can be induced in Purkinje cells after colchicine injection into the uninjured adult cerebellum, indicating that their expression could be controlled by retrograde signals. To assess whether myelin-associated neurite growth inhibitory proteins contribute to this regulation, we applied the neutralizing antibodies IN-1 against one of the main inhibitory components of central myelin (NI-250) either in vivo or in vitro to organotypic cerebellar cultures. Application of IN-1 antibodies induces the upregulation of c-Jun, JunD, and NADPH diaphorase in Purkinje cells, showing that their expression is suppressed constitutively by myelin-associated neurite growth inhibitors. Thus, the inhibitory activity of the IN-1 antigen on axon growth is not restricted to the control of growth cone motility but also involves a retrograde regulation of gene expression in adult central neurons.

Age Factors↗

PubMed1998

Plasticity of the olivocerebellar pathway.

The adult olivocerebellar axons and their terminal arbours, the climbing fibres, are capable of remarkable structural plasticity, regulated through their interaction with Purkinje cells. When these cells are deleted,terminal climbing fibre branches retract. In contrast,there is a vigorous outgrowth of entire terminal arbours when extra postsynaptic neurones are available. The new connections lead to a functional, highly specific pattern of innervation at the single Purkinje cell level and are topographically organized according to the principles of the original projection map.A reversible climbing fibre retraction occurs following depression of electrical activity of the cerebellar cortex. These remarkable plastic properties, together with the fact that these neurones express several growth-associated genes constitutively, suggest that the climbing fibre synapses might be adjusted dynamically to participate in physiological plasticity.

Animals↗

PubMed1998

Postsynaptic current mediated by metabotropic glutamate receptors in cerebellar Purkinje cells.

In rat cerebellar slices, repetitive parallel fiber stimulation evokes an inward, postsynaptic current in Purkinje cells with a fast component mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and a slower component mediated by metabotropic glutamate receptors (mGluR). The mGluR-mediated excitatory postsynaptic current (mGluR-EPSC) is evoked selectively by parallel fiber stimulation; climbing fiber stimulation is ineffective. The mGluR-EPSC is elicited most effectively with increasing frequencies of parallel fiber stimulation, from a threshold of 10 Hz to a maximum response at approximately 100 Hz. The amplitude of the mGluR-EPSC is a linear function of the number of stimulus pulses without any apparent saturation, even with >10 pulses. Thus mGluRs at the parallel fiber-Purkinje cell synapse can function as linear detectors of the number of spikes in a burst of activity in parallel fibers. The mGluR-EPSC is present from postnatal day 15 and persists into adulthood. It is inhibited by the generic mGluR antagonist (RS)-a-methyl-4-carboxyphenylglycine and by the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid at a concentration selective for mGluR1. Although the intracellular transduction pathway involves a G protein, the putative mediators of mGluR1 (phospholipase C and protein kinase C) are not directly involved, indicating that the mGluR-EPSC studied here is mediated by a different and still unidentified second-messenger pathway. Heparin, a nonselective antagonist of inositol-trisphosphate (IP3) receptors, has no significant effect on the mGluR-EPSC, suggesting that also IP3 might be not required for the response. Buffering intracellular Ca2+ with a high concentration of bis-(o-aminophenoxy)-N,N,N', N'-tetraacetic acid partially inhibits the mGluR-EPSC, indicating that Ca2+ is not directly responsible for the response but that resting Ca2+ levels exert a tonic potentiating effect on the mGluR-EPSC.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Targeted overexpression of the neurite growth-associated protein B-50/GAP-43 in cerebellar Purkinje cells induces sprouting after axotomy but not axon regeneration into growth-permissive transplants.

B-50/GAP-43 is a nervous tissue-specific protein, the expression of which is associated with axon growth and regeneration. Its overexpression in transgenic mice produces spontaneous axonal sprouting and enhances induced remodeling in several neuron populations (; ). We examined the capacity of this protein to increase the regenerative potential of injured adult central axons, by inducing targeted B-50/GAP-43 overexpression in Purkinje cells, which normally show poor regenerative capabilities. Thus, transgenic mice were produced in which B-50/GAP-43 overexpression was driven by the Purkinje cell-specific L7 promoter. Uninjured transgenic Purkinje cells displayed normal morphology, indicating that transgene expression does not modify the normal phenotype of these neurons. By contrast, after axotomy numerous transgenic Purkinje cells exhibited profuse sprouting along the axon and at its severed end. Nevertheless, despite these growth phenomena, which never occurred in wild-type mice, the severed transgenic axons were not able to regenerate, either spontaneously or into embryonic neural or Schwann cell grafts placed into the lesion site. Finally, although only a moderate Purkinje cell loss occurred in wild-type cerebella after axotomy, a considerable number of injured transgenic neurons degenerated, but they could be partially rescued by the different transplants placed into the lesion site. Thus, B-50/GAP-43 overexpression substantially modifies Purkinje cell response to axotomy, by inducing growth processes and decreasing their resistance to injury. However, the presence of this protein is not sufficient to enable these neurons to accomplish a full program of axon regeneration.

Animals↗

PubMed1997

Reestablishment of the olivocerebellar projection map by compensatory transcommissural reinnervation following unilateral transection of the inferior cerebellar peduncle in the newborn rat.

It is unclear whether reparative processes in the injured mammalian brain are able to restore the topographic organisation of neuronal connections. To address this question, we have investigated the plasticity of the olivocerebellar system. This pathway has a precise topographic arrangement, in which subsets of inferior olivary neurons project to parasagittally oriented Purkinje cell compartments. Following unilateral transection of the inferior cerebellar peduncle in newborn rats, axons from the contralateral projection cross the cerebellar midline and reinnervate the deafferented hemicerebellum. By this experimental approach, we first analysed the behaviour of calcitonin gene-related peptide (CGRP)-immunoreactive climbing fibres. This marker is transiently expressed by a subset of developing inferior olivary axons, which terminate in the cerebellar cortex into several parasagittal strips. We show that transcommissural axons reestablish the original pattern of climbing fibre bands within a few days after lesion. Then, in adult animals injured at birth, we assessed whether the newly formed climbing fibre bands align with zebrin II+/- Purkinje cell compartments, as in normal conditions. The newly formed projection is organised in parasagittally oriented strips which mirror the distribution of their counterparts on the intact side and are precisely aligned to the heterogeneous Purkinje cell compartments. In addition, the patchy distribution of olivo-nuclear fibres suggests that specific reinnervation is also achieved in the deep nuclei. Thus, transcommissural olivocerebellar reinnervation is not random, but it is regulated by selective interactions between distinct subsets of olivocerebellar axons and target neurons aimed at reestablishing the correct projection map.

Animals↗

PubMed1997

Italian grants.

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Financing, Organized↗

PubMed1997

The early phase of horizontal optokinetic responses in the pigmented rat and the effects of lesions of the visual cortex.

Horizontal optokinetic responses of pigmented rats were studied both in intact animals and in animals that had received lesions of the visual area of the cerebral cortex. In response to uniform velocity stimulation, there was an initial phase of rapid acceleration, larger than that reported in earlier studies, followed by a period of fairly uniform acceleration until the eye velocity approached that of the stimulus. As reported previously, responses to monocular stimulation were highly asymmetric, with the responses to nasotemporal stimulation being much weaker than those to temporonasal stimulation. Responses to sinusoidal stimulation were also studied. No significant effect of cortical lesions on the responses was seen.

Animals↗

PubMed1997

Reciprocal trophic interactions between climbing fibres and Purkinje cells in the rat cerebellum.

In the adult cerebellum both the climbing fibre arbour and the Purkinje cell are very plastic and each element is able to exert a remarkable action on the other one. The adult phenotype of the Purkinje cell is strictly dependent on the presence of its climbing fibre arbour. When the climbing fibre is missing, the Purkinje cell undergoes a hyperspiny transformation and becomes hyperinnervated by the parallel fibres. However, this change is fully reversible. The climbing fibre-deprived Purkinje cell is able to elicit sprouting of nearby located intact climbing fibres and the new arbour is able to fully restore synaptic connections which appear normal both morphologically and functionally. Multiple climbing fibre innervation of a single Purkinje cell persists in the adult hypogranular cerebellum. The different fibres are distributed to separate dendritic regions, suggesting a local competition between the different arbours for their territory. It is postulated that in the intact rat, an activity dependent mechanism of the parallel fibre favours the predominance of one arbour with the elimination of its competitors. When the Purkinje cell is deleted, the climbing fibre arbour becomes heavily atrophic and reduced in size. The analysis of the pattern of this atrophy indicates that the climbing fibre arbour is made by two compartments: a proximal one, whose survival depends on the integrity of the inferior olive, and a distal one, which represents the true pre-synaptic site, which strictly depends on the target. The climbing fibre terminal arbour is able to extend its territory of innervation not only when adult intact climbing fibres are confronted with nearby denervated Purkinje cells, but also when an embryonic cerebellum is grafted onto the surface of an adult unlesioned cerebellum. In this case, collaterals of intact climbing fibre arbours elongate through the pial surface, enter the graft to innervate the Purkinje cells. This growth is likely under the influence of a tropic signal released by the embryonic Purkinje cells. This suggests that the sprouting observed in the adult rat following a subtotal inferior olive lesion is also triggered by a similar factor. The axonal elongation and the consequent synaptogenesis are likely guided by local cues. In this condition, the distribution of the new collateral reinnervation occurs within its projectional map. In addition, when the inferior cerebellar peduncle is sectioned at birth, the climbing fibres of the non-deafferented hemicerebellum emit collaterals which cross the midline and innervate cerebellar strips which are symmetrically positioned relative to the intact side. In the grafting experiments, both the migrated and non-migrated Purkinje cells show the typical electrophysiological properties of the mature cerebellum. These data show that the disappearance of neuronal elements is not a necessary prerequisite to allow new neurones to become fully morphologically and functionally integrated into an adult brain. The reciprocal trophic influence between the climbing fibres and the Purkinje cells shown in the present series of experiments are likely operative in the adult brain not only in pathological conditions and they could give a basic contribution to the synaptic plasticity underlying learned behaviour.

Animals↗

PubMed1997

Intrinsic properties and environmental factors in the regeneration of adult cerebellar axons.

The success of axon regeneration in the adult mammalian brain depends on the presence of growth-permissive environmental conditions as well as on specific properties of the affected neurons. To investigate the relative contribution of extrinsic cues and intrinsic determinants to reparative processes we have investigated the regenerative properties of olivocerebellar and Purkinje cell axons. When these axon populations are severed in the cerebellar white matter and confronted with embryonic neural grafts of cerebellar or extracerebellar origin, the former vigorously regenerate into the transplant, whereas the latter invariably fail to do so (Rossi et al., 1995). The same response occurs when dissociated Schwann cells are implanted in the lesion site: Purkinje cell axons fail to regrow, whereas olivocerebellar fibres regenerate for considerable distances. Within the graft, regenerating fibres follow tortuous courses along Schwann cell bundles and sometimes end with poorly developed terminal plexuses. Some of them, however, succeed in crossing the graft and grow further into the host cortex, where they break into fine terminal branches confined to the granular layer. The remarkable regenerative response of olivocerebellar axons revealed by these experiments might be an intrinsic reaction of the affected neurons to axon injury or it might be elicited by growth promoting cues derived from the grafts. To elucidate this point we have undertaken the investigation of cellular changes occurring in adult inferior olivary neurons following the transection of the inferior cerebellar peduncle. Our results show that axotomy induces a series of cellular changes, or reparative and regressive character, which ultimately lead to cell death. Interestingly, however, these modifications are not uniformly distributed throughout the whole inferior olive. (i) Neuronal atrophy and degeneration progress more rapidly in the PO and DAO than in the MAO. (ii) A subpopulation of inferior olivary neurons become reactive for NADPH-diaphorase histochemistry, and their preferential localisation in the MAO suggests that this modification is related to the longer survival of these cells after axotomy. (iii) The developmentally regulated calcitonin gene-related peptide (CGRP) is reexpressed by a subset of neurons in the caudal nuclear compartments. These results further emphasise the conclusion that the dissimilar regenerative response of Purkinje cell and olivocerebellar axons confronted with permissive environmental conditions is due to different intrinsic properties of these neuronal populations. The reexpression of developmentally regulated substances by axotomised inferior olivary neurons suggests that their reparative reaction is triggered by axon injury. However, the pattern of growth of regenerating olivocerebellar axons is strongly conditioned by environmental constraints, which, in the present experimental conditions, do not allow them to reattain denervated Purkinje cells.

Animals↗

PubMed1997

Olivocerebellar axon regeneration and target reinnervation following dissociated Schwann cell grafts in surgically injured cerebella of adult rats.

The ability of Schwann cells to induce the regeneration of severed olivocerebellar and Purkinje cell axons across an injury up to their deafferented targets was tested by transplanting freshly dissociated cells from newborn rat sciatic nerves into surgically lesioned adult cerebella. The grafted glial cells consistently filled the lesion gap and migrated into the host parenchyma. Transected olivocerebellar axons vigorously regenerated into the graft, where their growth pattern and direction followed the arrangement of Schwann cell bundles. Although some of these axons terminated within the transplant, many of them rejoined the cerebellar parenchyma beyond the lesion. Here, their fate depended on the territory encountered. No growth occurred in the white matter. Numerous fibres penetrated into the granular layer and formed terminal branches that remained confined within this layer. A few of them, however, regenerated up to the molecular layer and formed climbing fibres on Purkinje cell dendrites. By contrast, the growth of transected Purkinje cell axons into the grafts was very poor. These results underscore the different intrinsic responsiveness of Purkinje cell and olivocerebellar axons to the growth-promoting action of Schwann cells, and show that the development and outcome of the regenerative phenomena is strongly conditioned by the spatial organization and specific features of the environmental cues encountered by the outgrowing axons along the course they follow. However, Schwann cells effectively bridge the lesion gap, induce the regeneration of olivocerebellar axons, and direct their growth up to the deafferented host cortex, where some of them succeed in reinnervating their natural targets.

Animals↗

PubMed1996

Increase of B-50/GAP-43 immunoreactivity in uninjured muscle nerves of MDX mice.

Lack of dystrophin in mdx mice leads to muscle fibre degeneration followed by the formation of new myofibres. This degeneration-regeneration event occurs in clusters. It is accompanied by inflammation and remodelling of the intramuscular terminal nerve fibres. Since the growth-associated protein B-50/GAP-43 has been shown to be involved in axonal outgrowth and synaptic remodelling following neuronal injury, we have investigated the presence of B-50 in gastrocnemius and quadriceps muscles of mdx mice. Using immunocytochemistry we demonstrate increased presence of B-50 in terminal nerve branches at motor endplates of mdx mice, particularly in the clusters of de- and regenerating myofibres. In comparison, the control mice displayed no B-50 immunoreactivity in nerve fibres contacting motor endplates. Our findings indicate that during axonal remodelling and collateral sprouting the B-50 level in the terminal axon arbours is increased although there is no direct injury to the motoneurons. We suggest that the degenerating target and/or the inflammatory reaction induces the increased B-50 level in the motoaxons. The increased B-50 may be important for sprouting of the nerve fibres and re-establishment of synaptic contacts, and in addition, for maturation and survival of the newly formed myofibres.

Acetylcholinesterase↗

PubMed1996

Postsynaptic currents and short-term synaptic plasticity in Purkinje cells grafted onto an uninjured adult cerebellar cortex.

It has been shown recently that embryonic Purkinje cells grafted extraparenchymally into an intact cerebellum, in the absence of any sign of damage, are able to migrate into the host molecular layer where they receive a climbing fibre innervation. Using the same technique, we investigated the development of the electrophysiological properties of the synapses between the grafted cells and their main afferents. Purkinje cells either in the graft or having migrated into the molecular layer of the host were recorded using the whole-cell patch-clamp method in acutely prepared slices 17-112 days after grafting. Spontaneous postsynaptic currents with a single-exponential decay and mediated by GABAA receptors were very similar to those described in normal Purkinje cells. Excitatory postsynaptic currents (EPSCs) evoked by climbing fibre and by parallel fibre stimulation were blocked by an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate antagonist, and displayed the linear current-voltage relation typical of postnatal Purkinje cells. The attainment of normal functional properties by the adult axons at the newly formed synaptic sites was shown by the expression of short-term facilitation of parallel fibre EPSCs and of short-term depression of climbing fibre EPSCs. The grafted Purkinje cells showed climbing fibre polyinnervation 17-20 days after grafting which evolved to monoinnervation at 23-45 days, confirming the completion of the developmental programme up to maturation. Our experiments support the view that the adult intact brain is able to accept and integrate an additional number of neurons which show fully mature electrophysiological properties which are electrophysiologically indistinguishable from those of the host neurons.

Animals↗

PubMed1996

Topographically organized climbing fibre sprouting in the adult rat cerebellum.

Adaptive recovery following brain injury requires the topography of projection maps to be restored. In the adult mammalian brain, the regeneration of severed axons does not normally occur and repair mainly relies on collateral reinnervation from uninjured neurons. Although reinnervation can be target specific at the single cell level, it is not known if the new connections are organized correctly. The normal olivocerebellar projection had precise topography in which subnuclei of the inferior olive terminate as climbing fibres on chemically defined bands of cerebellar Purkinje cells. This precision has been exploited to determine the topography of climbing fibre sprouting following an inferior olive lesion in the adult rat. Collateral reinnervation was found to respect the boundaries between the Purkinje cell compartments. Thus, topographical cues are available in the adult during post-lesion plasticity to guide the restoration of the olivocerebellar projection map.

Animals↗

PubMed1995

Different climbing fibres innervate separate dendritic regions of the same Purkinje cell in hypogranular cerebellum.

Electrophysiological experiments have shown that in hypogranular cerebella the Purkinje cells are innervated by several climbing fibres. The aim of this paper is to provide morphological evidence for this multiple innervation and to describe the topographical distribution of the different climbing fibres onto the somadendritic region of the Purkinje cell. Experiments have been performed in hypogranular adult Wistar rats lesioned during the first postnatal week by methylazoxymethanol (MAM) or by X-irradiation. Purkinje cells were labelled by an anti-calbindin antibody, whereas climbing fibres were visualised by means of Phaseolus vulgaris leucoagglutinin. Purkinje cells showed variable degrees of abnormality and displacement. Climbing fibres made contact with the dendrites of all kinds of Purkinje cells, including those ectopically positioned whose dendrites branched in the white matter. This shows that Purkinje cells can develop dendritic branching in the absence of granule cells and maintain the capability of interacting with their proper afferents, even when they are severely affected and displaced. In four Purkinje cells we have been able to follow the course of two climbing fibre terminal arbourisations. Almost no terminal branches were present around the Purkinje cell soma, and the whole arbour covered the proximal two-thirds of the Purkinje cell dendritic tree. These arbourisations, after an initial common course along the primary dendrite, distributed to separate dendritic regions. The observation of a single labelled climbing fibre covering a limited region of the dendritic tree was more common. As this finding is never observed in control material, it is concluded that the remaining region is covered by another unlabelled climbing fibre belonging to a different inferior olive neurone. These results represent a morphological demonstration of multiple climbing fibre innervation of the adult Purkinje cell. The maintenance of polyinnervation in the adult, which is consequent to the loss of granule cells, is not associated with a defect in the peridendritic translocation of the olivary arbour. In addition, the strict segregation of the different climbing fibres to distinct territories of the Purkinje cell dendritic tree suggests that each terminal arbourisation acts as a functionally independent unit and prevents other competitors from invading its own target domain.

Afferent Pathways↗

PubMed1995

Citation analysis.

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Bibliometrics↗

PubMed1995

Influence of eye motion on adaptive modifications of the vestibulo-ocular reflex in the rat.

While sustained retinal slip is assumed to be the basic conditioning stimulus in adaptive modifications of the vestibulo-ocular reflex (VOR) gain, several observations suggest that eye motion-related signals might also be involved. We oscillated pigmented rats over periods of 20 min around the vertical axis, at 0.3 Hz and 20 degrees/s peak velocity, in different retinal slip and/or eye motion conditions in order to modify their VOR gain. The positions of both eyes were recorded by means of a phase-detection coil system with the head restrained. The main findings came from the comparison of two basic conditions--including their respective controls--in which one or both eyes were reversibly immobilised by threads sutured to the eyes. In the first condition the animals were rotated in the light with one eye immobilised and the other eye free to move but covered. Rotation in the light in this open-loop condition immediately elicited high-gain compensatory eye movements of the non-impeded, covered eye. At the end of this training procedure, the VOR gain increased by 43.2%. In the second condition, both eyes were immobilised and one eye was covered. The result was an increase in the VOR gain of 26.3%. These two conditions were similar as to the visuo-vestibular drive during the exposure, but different as to the resulting--and allowed--eye motion, showing that the condition where the larger eye movements occurred yielded the larger VOR gain change. Our data support the idea proposed by Collewijn and Grootendorst (1979, p. 779) and Collewijn (1981, p. 146) that "[retinal] slip and eye movements seem to be relevant signals for the adaptation of the rabbit's visuo-vestibular oculomotor reflexes".(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1994

Exposure to kainic acid mimics the effects of axotomy in cerebellar Purkinje cells of the adult rat.

We have investigated the long-term structural changes which affect Purkinje cells exposed to a single dose of kainic acid. Following intraparenchymal injection of the excitotoxin in the cerebellar cortex (1 microliter of a 1 mg/ml solution), Purkinje cells which survived within the lesioned area or close to its edges showed remarkable axonal abnormalities, involving the formation of torpedoes, hypertrophy of recurrent collaterals and atrophy of the corticofugal portion of the axon. In addition, their dendritic trees were often affected by conspicuous regressive alterations. The climbing fibres contacting these Purkinje cells were characterized by thick perisomatic plexuses, whereas their peridendritic branches were atrophic. The dendrites innervated by such atrophic olivary arbours were studded with huge numbers of newly formed spines. These alterations were already present a few days after kainic acid administration and persisted for the total period of observation of 6 months after the lesion. The remarkable similarity between the abnormalities of Purkinje cells exposed to kainic acid and those observed after axotomy indicates that in these two conditions common mechanisms determine analogous long-lasting modifications in the affected neurons. It is proposed that kainic acid-induced intracellular calcium overload disrupts cytoskeletal components and impairs axonal transport, thus depriving the affected Purkinje cells of retrograde trophic influences from their target neurons. As a consequence the affected neurons undergo long-lasting regressive modifications and compensatory remodelling phenomena.

Animals↗