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C Sotelo

Publications and source records attributed to C Sotelo.

At least 109 records · Page 6Linked to original sources
PubMed1986

Neuronal migration and dendritic maturation of the medial cerebellar nucleus in rat embryos: an HRP in vitro study using cerebellar slabs.

The morphological maturation of medial nuclear neurons of fetal rat cerebella was studied using an in vitro assay. Neurons of this nucleus were identified in isolated preparations of rhombencephalon between embryonic days 16 and 20 (E16-E20) by the intracerebellar decussation of their outgrowing axons within the uncinate fascicle. A small crystal of horseradish peroxidase (HRP) applied either in the region containing the inferior cerebellar peduncle or, preferably, in the lateral cerebellum retrogradely labeled contralateral medial nuclear neurons. In the youngest embryos (E16-E17), HRP-marked neurons were situated rostrally at the dorsal surface of the cerebellum. By E18, the cell mass containing labeled neurons had shifted in a rostrocaudal and dorsoventral direction and finally reached the adult position in E19-E20 embryos. Dendritic differentiation of these neurons followed a similar positional gradient, closely corresponding to the pattern of temporal development. From the most immature monopolar forms located dorsally to the virtually adult stellate neurons in a ventral position, it was possible to trace a continuum of intermediary forms grouped into six well-defined stages. Immature monopolar cells first became transversely bipolar. Then, they changed orientation, assuming a longitudinal radial direction. During this stage, neurons sank into the cerebellar parenchyma. As they reached their final destination, these neurons gradually developed dendrites which radiated from the cell body in an adult-like pattern. It is concluded that the medial nuclear neurons occupy a superficial dorsal position in early phases of cerebellar ontogeny, thereafter undergoing a second, inward migration. The main stages of neuronal dendritic differentiation occur between E16 and E20, indicating that the ingrowth of afferent in puts to the medial nucleus most probably occurs rather early and is concomitant with dendritic development.

Animals↗
PubMed1986

Growth and differentiation of cerebellar suspensions transplanted into the adult cerebellum of mice with heredodegenerative ataxia.

Cell suspensions from cerebellar primordia of 12-day mouse embryos were grafted into the cerebellum of 4-month-old Purkinje cell degeneration (pcd) mutant mice and examined 2-3 months later. In contrast to those of nontreated mutants, all of the grafted cerebella exhibited Purkinje cells that had migrated into the molecular layer, where they were clustered over its superficial two-thirds. These Purkinje cells develop flattened dendritic trees perpendicular to bundles of parallel fibers. Ultrastructural examination of their synaptic inputs and outputs disclosed that (i) as in normal cerebella, climbing fibers and axons from basket and stellate cells synapse on thick dendrites, whereas parallel fibers almost exclusively contact the distal spiny branchlets, and (ii) a substantial number of Purkinje cell axons reach their appropriate targets in the deep cerebellar nuclei, where they establish synaptic connections on large and small neurons. These results indicate that embryonic Purkinje cells grafted into the cerebellum of adult mice with heredodegenerative ataxia integrate themselves very specifically into the cerebellar circuitry of the recipient mouse, where they can replace the missing Purkinje cells. They also provide a morphological basis favoring the notion of functional restorative capabilities of neural grafts in systems in which neurons are connected in an almost point-to-point manner.

Animals↗
PubMed1985

Development of the spinocerebellar system in the postnatal rat.

The distribution of spinocerebellar projections from birth to adulthood in rats was analyzed by anterograde and retrograde tracing methods. A correlation between mossy fiber synaptogenesis and the establishment of spinocerebellar topography was also investigated with electron microscopy. Experiments with retrograde transport techniques indicate that the spinal axons reach the cerebellum in two successive groups: the first one, appearing prenatally, contains axons from neurons in the central cervical nucleus, Clarke's column, the sacral nucleus of Stilling, as well as from border cells. The second group, which reaches the cerebellum by P3, arises from new neurons of the same nuclear regions and from scattered cells of the spinal gray matter. The distribution and the morphological appearance of the spinal cells change between P1 and P3 and give the adult pattern by P7. The establishment of spinocerebellar projections occurs in four successive stages. In a first stage, spinal axons reach the cerebellum and occupy the prospective white matter of the anterior vermal lobe and of the pyramis. Later, during a "waiting" stage between P1 and P3, the spinal fibers become denser in the central white matter of both their anterior and posterior target zones but do not penetrate the gray matter. From P3 to P5 the protocolumnar stage takes place, and spinal axons invade the granular layer of the anterior lobe, where they begin to be organized in nascent sagittal columns. At the end of this stage, identifiable synaptic contacts between mossy terminals and granule cell dendrites are first observed in the anterior lobe by electron microscopy. In the pyramis, invasion of the granular layer begins only at P5. Between P5 and P7 the low intercolumnar dispersion of spinal fibers disappears and the projection reaches its fourth and final stage, characterized by a columnar organization corresponding to the adult pattern of the spinocerebellar projection. These results indicate that (1) the adult pattern of spinocerebellar projections is attained by P7. (2) The asynchronous invasion of the gray matter in the anterior and posterior lobes may be related to the chronology of mossy fiber maturation in these regions. (3) There is a temporal correlation between the columnar organization of the spinal axons and the appearance of the earliest-maturing mossy rosettes. However, a clear relationship between synaptogenesis and topographic organization could not be demonstrated.

Animals↗
PubMed1985

Compensatory climbing fiber innervation after unilateral pedunculotomy in the newborn rat: origin and topographic organization.

In neonatal rats the unilateral transection of the cerebellar peduncles causes a fast and complete degeneration of the contralateral inferior olive. Axons from the remaining olive recross the cerebellar midline and partially innervate the deprived hemicortex. Analysis of the topographic organization of this compensatory projection studied with the axonal tracing method provided the following results: Retrograde tracing experiments revealed that the bulk of compensatory afferents originates from neurons in the ipsilateral medial accessory olive, especially from its medial region, whereas afferents from the principal olive and the dorsal accessory olive contribute to a much lesser degree. In case of incomplete neonatal pedunculotomy, neurons with a similar location in the ipsilateral intact olive still contribute to the innervation of the partially deprived hemicortex, along with the atrophic contralateral olive. Moreover, these experiments revealed important information about the organization of the compensation. Although its specificity was not totally maintained, the mediolateral distribution of sprouted afferents in the cerebellum matched the caudorostral disposition of parent neurons in the olive, as in the case in normal olivocerebellar projection. Anterograde studies showed that compensatory fibers recrossing the cerebellar midline spread throughout the whole extent of the deprived cortex and terminate solely in the molecular layer as typical climbing fibers. The latter were not homogeneously distributed, their density being markedly reduced according to a mediolateral gradient. Compensatory projection followed a sagittal striped pattern, as does the normal climbing fiber projection. Moreover, if the cortex is divided broadly into vermal, intermediate, and hemispheral regions, an apparent reciprocity seems to exist concerning the relative involvement of the various cortical subdivision in both hemicerebella. Our present results indicate that the immature olivocerebellar system is capable of anatomical plasticity, although to a limited extent. More important, they suggest that a certain degree of specificity is maintained during the process of sprouting, resulting in a topographical arrangement of the transcommissural climbing fiber projection. This indicates, in turn, that cues which guide the growth of olivocerebellar fibers during normal development could also direct the compensatory innervation.

Animals↗
PubMed1985

Transient biochemical compartmentalization of Purkinje cells during early cerebellar development.

It has recently been observed that during early cerebellar development--from embryonic Day 17 to postnatal Day 3 in the rat--only certain discrete clusters of Purkinje cells (PCs) are immunoreactive to cyclic GMP-dependent protein kinase (cGK). In contrast, at later stages and in the adult, all the PCs are immunoreactive. These results obtained with cGK suggest a transitory intrinsic heterogeneity in the immature cerebellar cortex. It seemed therefore interesting to investigate the distribution of other PC markers during early development in the rat and in other species. The results presented here were obtained with two other antibodies--against vitamin D-dependent calcium binding protein and against Purkinje cell specific glycoprotein--which, like cGK, label all adult PCs. Each antibody gave a different and reproducible mosaic of positive and negative clusters of PCs in the perinatal cerebellum, thus indicating a transient biochemical compartmentalization resulting from the differential expression of parts of the same genotype by clusters of PCs. This compartmentalization in concomitant with the ingrowing of the cerebellar afferents. Once synaptogenesis starts, the biochemical heterogeneity of PCs disappears.

Animals↗
PubMed1984

Postnatal development of the inferior olivary complex in the rat. II. Topographic organization of the immature olivocerebellar projection.

The state of organization of the olivocerebellar projection in newborn and 5-day-old rats has been analyzed by autoradiography of anterogradely transported 3H-leucine, as well as by retrograde transport of horseradish peroxidase. The efferent axons of the inferior olivary neurons are already present and already highly organized in the cerebellum of newborn rats. Most of the autoradiographic labelling subsequent to the injection of 3H-leucine into the inferior olive is seen in the subcortical medullary zone. Labelled axons only partially invade the gray matter, where they reach the zone occupied by randomly distributed Purkinje cells. At this immature stage, olivocerebellar projections are already entirely crossed and distributed according to a pattern which is similar to the adult. At the fifth postnatal day olivocerebellar projections have moved from the medullary zone toward the interface between the molecular and the granular layers where Purkinje cells have arranged in a monolayer. Evidence for translocation of climbing fibers from their perisomatic to their peridendritic position is already distinct in these young cerebella. Combination of anterograde and retrograde fiber system tracing experiments discloses the following crossed topography of olivocerebellar projections: The caudal half of the medial accessory olive projects mainly to the vermis of the posterior lobe, whereas its rostral half projects to the flocculus, paraflocculus, and the intermediate cortex. The principal olive, ventral and dorsal lamellae, supplies climbing fiber inputs to the hemispheric cortex. The caudal half of the dorsal accessory olive projects to the lateral portion of the vermis of the anterior lobe, whereas neurons in its rostral half send their axons toward the intermediate cortex. This topographic arrangement is, therefore, similar to that reported for adult mammals. The present results, alone or when compared with those obtained during other studies on the synaptogenesis between climbing fibers and Purkinje cells, allow the following conclusions: The climbing fibers enter the cerebellar cortex before Purkinje cells have reached the developmental phase compatible with synaptogenesis. They wait in the medullary white matter until appropriate maturation of their cellular targets. Olivocerebellar topography is roughly similar in newborn, 5-day -old, and adult rats. Synaptogenesis between climbing fibers and Purkinje cells, which is known not to start before the second postnatal day, is not necessary for the establishment of the topographic organization of the olivocerebellar projection.

Animals↗
PubMed1984

Homotopic and heterotopic transplantations of quail tectal primordia in chick embryos: organization of the retinotectal projections in the chimeric embryos.

To study the adaptative capabilities of the retinotectal system in birds, the primordium of one optic tectum from 12-somite embryos of Japanese quail was transplanted either homotopically , to replace the ablated same primordium, or heterotopically, to replace the ablated dorsal diencephalon in White Leghorn chick embryos of the same stage. The quail nucleolar marker was used to recognize the transplants. The cytoarchitecture of the tecta and the retinal projections from the eye contralateral to the graft were studied on the 17th or 18th day of incubation in the chimeric embryos by autoradiographic or horseradish peroxidase tracing methods. Morphometric analysis was applied to evaluate the percentage of the tectal surface receiving optic projections. It was observed that: (i) quail mesencephalic alar plate can develop a fully laminated optic tectum even when transplanted heterotopically; (ii) retinal ganglion cells from the chick not only recognize the tectal neurons of the quail as their specific targets in homotopic grafts, but the optic fibers deviate to innervate the heterotopically grafted tectum; (iii) in the presence of a graft, the chick retina is unable to innervate a tectal surface of similar or larger size than that of the control tectum; (iv) tectal regions devoid of optic projections, whether formed by donor or by host cells, always present an atrophic lamination; (v) the diencephalic supernumerary optic tectum competes with and prevails over the host tectum as a target for optic fiber terminals.

Animals↗
PubMed1984

Postnatal development of the inferior olivary complex in the rat. III. A morphometric analysis of volumetric growth and neuronal cell number.

The overall volume of the three main inferior olivary (ION) subnuclei increases four-fold between the day of birth (PO) and P21. The rate of this increase is uneven; between P10 and P15 there is an abrupt acceleration which parallels the period of intense synaptogenesis and maturation of the neuropil. The growth of the various subnuclei occurs in an almost synchronous manner. A study discloses that the postnatal volumetric increase is the result of the development of the neuropil and the glial cells. The numerical estimation of neuronal perikarya was made for each ION subnucleus from P0 to P33. However, due to methodological problems, the quantitation becomes reliable only from P5 onwards. From P5 to P8, there is a small (10%) but consistent decrease in the number of olivary neurons, a decrease which is homogeneously shared by the 3 main subnuclei. This phase of reduction in neuronal numbers, indicative of cellular death, is followed by an increase of similar magnitude, between P10 and P15. Since the phase of apparent olivary cell death coincides with the peak of the regression of the multiple innervation of Purkinje cells (PCs) by climbing fibers (CFs), both processes might be interrelated. However, the slight amplitude of the cell death is inadequate to fully explain the whole process of synaptic regression. These results indicate a dual nature of the mechanism underlying the establishment of the one-to-one relationship between CFs and PCs: a small proportion of the regression results from cell death, while the largest proportion must be the result of a loss of collaterals from the olivary axons at the origin of the CFs. The problem of the increase in the number of ION neurons between P10 and P15 is discussed in relation to recent morphometric data indicating a late increase in the number of PCs of the cerebellum.

Animals↗
PubMed1984

Asynchrony in the expression of guanosine 3':5'-phosphate-dependent protein kinase by clusters of Purkinje cells during the perinatal development of rat cerebellum.

The early maturation of Purkinje cells was studied by immunocytochemistry in the rat cerebellum. The antiserum against guanosine 3':5'-phosphate-dependent protein kinase used in this study has been shown previously to label specifically all Purkinje cells in the adult rat. Immunoreactive Purkinje cells are first observed at embryonic day 17, 2 days after the end of proliferation of this neuronal population. At this time, most of the labeled cells are situated in the subventricular zone, although some immunoreactive Purkinje cells have already reached the cortex. Between embryonic day 17 and birth, four clusters of immunoreactive Purkinje cells appear in each hemicerebellum. Their time course and their pathways of migration to the cortex were followed. The immunoreactive clusters are tailed by a fibre-like immunostained material. The pattern of the migrating clusters at embryonic day 19 is very similar to the pattern of the corticonuclear projection observed at birth. From comparison between sections of embryos processed either for immunocytochemistry or Cresyl Violet staining, it appears that all the Purkinje cells are not immunoreactive. Positive and negative clusters of Purkinje cells are sharply delineated, their cells never mix. Immunopositive and negative clusters of Purkinje cells coexist until postnatal day 3. However, from birth onwards, negative clusters begin progressively in a caudorostral sequence to express guanosine 3':5'-phosphate-dependent protein kinase and rapidly attain the same level of immunoreactivity as previously labeled clusters. From postnatal day 5 all the Purkinje cells are immunoreactive. It is concluded that a compartmentalization of the cerebellar cortex is present very early and is evidenced by differences in the biochemical maturation of Purkinje cells. The axons of Purkinje cells reach the deep nuclei, following the same pathways as the clusters of Purkinje cells migrating to the cortex. Therefore, the mechanisms regulating the selection of the migratory routes followed by each Purkinje cell cluster are essential for the achievement of the topography of the corticonuclear projection. The level of protein kinase immunoreactivity cannot be taken as an index of the overall maturation of Purkinje cells, because it does not always coincide with the expression of other makers of biochemical and morphological differentiation of these neurons. During the early establishment of the cerebellar maps, an asynchrony in the expression of parts of the same genotype in the Purkinje cells may help in the establishment of ordered connections.

Animals↗
PubMed1983

Postnatal development of the inferior olivary complex in the rat. I. An electron microscopic study of the medial accessory olive.

The postnatal development of the medial accessory olive (MAO) was studied in the rat from birth to adulthood. In newborn rats, the inferior olivary complex exhibited an adult cytoarchitectonic pattern, facilitating the precise delimitation of the MAO. Computer-assisted measurements of neuronal perikarya in 1 micron thick plastic sections revealed a 40% increase in perikaryal diameters from day of birth (PO) to the twenty-first postnatal day (P21). This growth takes place mainly during the first postnatal week, the phase of perikaryal maturation, whereas it is almost non-existent during the second week, the phase of sudden neuropil expansion. The ultrastructural study gave the following results: at P1-P5, only the neuronal perikarya have attained a certain degree of maturity. The neuropil is composed of profiles of unknown origin, among which growing dendrites are numerous, but mature synapses are scarce. By P7-P10, the cytological characteristics of the perikarya reached an adult stage. The dendrites begin to acquire their adult features by their emission of racemose protrusions and by their organization into protoglomerular formations. The most important step in the structural differentiation of the MAO was found to occur between P10 and P15. It is at this later age that the neuropil exhibits a complex neuronal organization similar to the adult, characterized by the presence of olivary glomeruli and of neuro-neuronal gap junctions. The fact that these electrotonic junctions appear a long time after the appearance of chemical synapses, indicates that the ontogeny of the MAO chemical transmission precedes electrical transmission. On P15 and thereafter, the maturation of the MAO proceeds mainly by increasing the number of synaptic connections and by glial differentiation. These structural developmental stages of the MAO were related to the different steps of functional development of the olivocerebellar system.

Animals↗
PubMed1982

Differentiation of cerebellar anlage heterotopically transplanted to adult rat brain: a light and electron microscopic study.

Pieces of cerebellar primordia from (days 14 or 15 of gestation) E14 or E15 rat embryos were dissected out and transplanted into a cavity of the occipital cortex and underlying hippocampus, over the superior colliculus of 2-month-old rats. The host animals were allowed to survive for 2 to 3 months. The cytoarchitectonic and the synaptic organizations were analyzed in 16 of such transplants. Only 4 of the implants established connections with the host brain through several thin peduncles composed of myelinated fibers. The remaining 12 implants survived in an extraparenchymal situation. Independently of its partial linking to the host brain, the graft grew and developed a cerebellar structure composed of nuclear and cortical regions. The latter exhibited normal lamination and foliation, and contained the five categories of neurons which characterize normal cerebellar cortex. Electron microscopic examination disclosed that the synaptic connections normally present in the cerebellar cortex were also formed in the implants with the exception of climbing fibers, which were absent. The cerebellar interneurons kept their normal topographic distribution and gave origin to numerous synapses which maintained their own specificity. Some mossy fibers were present in the granule cell layer at the center of typical glomeruli. However, abnormal synaptic arrangements were also observed within the neuropil of this granule cell layer. They consisted of pseudoglomerular formations composed of clusters of tightly packed small axon terminals covered by granule cell dendrites. The origin of these boutons was not established. Since they did not correspond to the classes of presynaptic elements normally synapsing on these dendrites, they constitute a new example of cerebellar heterologous synapses. Their presence could be related to changes in the cellular environment due to the rarity of mossy afferents. HRP tracing experiments, carried out in extraparenchymal transplants, have allowed us to determine that the corticonucleocortical loop of normal cerebellum is also developed in the implants. Nuclear neurons are at the origin of the mossy fibers involved in glomerular formations, whereas Purkinje cells project to the nuclear region. The establishment of these reciprocal connections could determine the functional stabilization of both kinds of cerebellar neurons and thus the long survival of extraparenchymal grafts. These results allow the conclusion that the presence of extracerebellar afferents is not necessary for the organotypic and synaptotypic differentiation of cerebellar anlage.

Animals↗
PubMed1982

Ultrastructural evidence for compensatory sprouting of climbing and mossy afferents to the cerebellar hemisphere after ipsilateral pedunculotomy in the newborn rat.

Unilateral section of the inferior and middle cerebellar peduncles was performed in rats at postnatal days 1 or 2. The ultrastructure of the cerebellar hemispheric cortex ipsilateral to the lesion was examined 3 months later. The absence of contralateral inferior olive and of ipsilateral middle peduncle, together with a marked regression of the contralateral pontine gray, were indicative of successful pedunculotomy. In spite of a relative atrophy of the hemisphere, its cytological structure was qualitatively normal. Mossy and climbing fibers were present and their terminal varicosities disclosed normal features. The density of climbing fiber terminals was reduced compared to control cerebellum, whereas the density of mossy terminals seemed unchanged. subsequent to the reduction of climbing afferents two subclasses, or types, of Purkinje cells were present: A "normal" type characterized by its climbing fiber innervation and a "hyperspiny" type devoid of climbing fiber. In some of the adult rats pedunculotomized at birth, section of the contralateral peduncles was performed 24 hours before fixation. Terminal degeneration of climbing and mossy fibers was observed in the neonatally deprived hemisphere, providing the proof that these fibers result from a compensatory transcommissural sprouting of afferents destined to the contralateral hemicerebellum. These results demonstrate that the cerebellar cortex neonatally deprive of its main afferents can be innervated by climbing and mossy fibers through a process of transcommissural sprouting. Although the newly formed synapses maintain their target specificity, a functional reorganization must occur because of the altered distribution of both systems of afferents.

Afferent Pathways↗
PubMed1981

Heterologous synapses upon Purkinje cells in the cerebellum of the Reeler mutant mouse: an experimental light and electron microscopic study.

The projections of the spinal cord upon the cerebellum of normal and Reeler mutant mice were compared by light and electron microscopic methods after hemicordotomy. In both genotypes this afferent system projects to the cerebellar cortex and to the roof nuclei. In the Reeler, there is an additional projection among the Purkinje cells and interneurons of the central cerebellar mass. In both normal and Reeler cerebellar cortex this mossy fiber system terminates as large glomeruli. In Reeler the spinal projection also gives rise to a smaller terminal which is distributed both to the cortex and the central cerebellar mass. In both genotypes the dendrites of granule cells and the somata and dendrites of Golgi cells are synaptic targets of the glomeruli of the cortical projection. In Reeler both the glomeruli and smaller terminals also form heterologous synaptic contacts with dendrite spines of heterotopic intracortical and subcortical Purkinje cells. In both genotypes the synapses are exclusively type I. A second class of heterologous synapse, a type I junction between axons of Golgi cells and Purkinje cell spines, is also recognized in electron micrographs. The present study is the first unequivocal demonstration by experimental hodologic method of heterologous synaptic junctions in the mammalian central nervous system. The existence of such junctions in the cytoarchitectonically anomalous cerebellum of this mutant emphasizes the critical role played by the cellular environment in shaping neural circuits in the developing nervous system.

Afferent Pathways↗
PubMed1981

Synaptic remodeling of serotonin axon terminals in rat agranular cerebellum.

In order to assess the influence of the target zone on the synaptic modeling of central serotonin (5-HT) axons, the 5-HT innervation of the posterior vermal cortex was studied by high resolution radioautography in both normal and X-ray-induced agranular rat cerebella, following topical application of [3H]5-HT. Two major systems of 5-HT afferents were identified in normal cerebellar cortex: (1) typical mossy fibers confined to the granular layer and (2) fine beaded axons diffusely distributed through all layers. The density of this innervation was estimated to be approximately 240,000 varicosities/cu.mm of cortex. The labeled mossy terminals all established synaptic contacts with the dendrites of granule cells. In contrast, only 3% of the varicosities belonging to the 'diffuse system' exhibited active zones in single thin sections, implying that less than 9% were actually engaged in junctional synaptic relationships. In the agranular cerebellar cortex, all 5-HT terminals belonging to the so-called 'diffuse system'. Their density was more than 8 times higher than in normal rat (2 million/cu.mm of cortex), an increase accounted for by the smaller volume of the experimental cerebellum. Thirty-five per cent of these 5-HT varicosities were seen in synaptic contact, indicating that all established at least one junctional complex. Most of these synapses were made on the branchlet spines of Purkinje cell dendrites, but some were also observed on the dendritic shafts of Golgi cells. Thus, in the absence of granule cells, the 5-HT innervation of rat cerebellar cortex evolves from a mostly 'non-junctional' into an entirely 'junctional' input. This finding indicates that the territory of innervation can exert a determinant influence on the synaptic modeling of incoming 5-HT afferents.

Afferent Pathways↗
PubMed1979

Influence of experimentally induced agranularity on the synaptogenesis of serotonin nerve terminals in rat cerebellar cortex.

The serotonin (5-HT) innervation of the posterior vermis was studied by high resolution radioautography in both normal and X-ray-induced agranular rat cerebella, following 3 h topical superfusion with 10(-4) M 3H-5-HT. In the normal cerebellar cortex, 5-HT axonal varicosities are scarce and only rarely exhibit the membrane differentiations characterizing synaptic contacts. In the agranular cerebellum, 5-HT terminals appear to have a much higher density than in normal controls, although their absolute number may not be significantly different when the important reduction in volume of this experimental cerebellum is taken into account. These terminals frequently show typical synaptic contracts. Most of them are established on the branchlet spines of Purkinje cell dendrites, but some are also observed on the shafts of Golgi cell dendrites. The 5-HT innervation of the cerebellar cortex thus undergoes important changes in the absence of granule cells. It is suggested that these modifications may be part of the general reorganization process of the cerebellar circuitry consequent on the early destruction of the external granular layer. This new example of synaptic remodelling could imply that the formation of cerebellar connectivity is modulated, to a certain extent, by the local cellular environment.

Animals↗