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C Sotelo

Publications and source records attributed to C Sotelo.

At least 127 records · Page 7Linked to original sources

Fate of presynaptic afferents to Purkinje cells in the adult nervous mutant mouse: a model to study presynaptic stabilization.

The hemispheric cerebellar cortex from 174- to 420-day-old nervous mice has been studied with Golgi, Cajal-reduced silver and electron microscopic techniques. In all mice, the existence of a continuous process of Purkinje cell death, indicated by the presence of few of these neurons in early stages of degeneration, has been established. The morphology of such degenerating cells, as well as the removal of the necrotic debris and the consecutive isolation of presynaptic fibers by glia are described. In the molecular layer, and in spite of the important Purkinje cell loss, numerous varicosities belonging to parallel fibers persist. They can be either synapsing on interneurons or concentrated in small clusters of 2-10 boutons covered by astrocytic processes. The synaptic investment of stellate and basket cells, as well as the length and the branching pattern of their dendritic fields are not significantly changed, besides the increase in afferent terminals deprived of their postsynaptic targets. Basket formations, as numerous as in control cerebellum, are forming a discontinuous row at the superficial third of the granular layer. Over 90% of these baskets are devoid of Purkinje cells, however, their ultrastructural features mimic those of the same terminals in control mice, with the exception that few of them can either establish heterologous synapses with granule cell dendrites, or develop gap junctions between them. The significance of the persistence of normal looking presynaptic elements long time after deprivation of their postsynaptic targets is discussed in relation to the role that function can play in the stabilization of synaptic contacts.

Afferent Pathways↗

Specificity of dopaminergic neuronal degeneration induced by intracerebral injection of 6-hydroxydopamine in the nigrostriatal dopamine system.

The neurotoxic specificity of injections of 6-hydroxydopamine (6-OHDA) into areas containing either dopamine (DA) cell bodies (substantia nigra) or DA axon terminals (striatum) was studied. This selective effect was compared to the unspecific effects of copper sulfate (CuSO4) injection and electrocoagulation. One to two days after unilateral nigral injection of 2 mug of either 6-OHDA or CuSO4 into the nigra the volume of the unspecific lesions around the tip of the cannula was very similar. Only the 6-OHDA-induced lesions were associated with elective degeneration of the nigral DA neurons. Ten days after the administration of the same compounds the gliosis in the substantia nigra was much more extensive in CuSO4-than in 6-OHDA-treated rats; however, the reduction of DA concentrations in the ipsilateral striatum was only noticeable after 6-OHDA (-62%). A somewhat similar decrease of striatal DA levels (-52%) was observed after large electrocoagulation of the substantia nigra. Ten days after 6-OHDA (8mug) or electrolytic lesion of the striatum the Km for DA, serotonin and choline uptakes were similar in the striata of both sides, suggesting that the uptake process in the non-damaged neurons of the lesioned side was functionally normal. Following electrolytic lesion of the striatum, serotonin and choline Vmax values were decreased to about the same extent as the striatal reduction in weight and DA levels. When directly administered into the striatum 6-OHDA also produced a decline in DA concentration and Vmax but in contrast did not affect serotonin and choline uptake (Vmax), suggesting that the drug specifically destroyed dopaminergic neurons. The present data confirm that selective DA denervation can be achieved when appropriate amounts of the drug are injected into brain tissue in order to limit the unspecific lesion.

Animals↗

Inferior olive: its role in motor learing.

Specific chemical lesion of the rat inferior olive by intraperitoneal administration of 3-acetylpyridine prevents recuperation from motor abnormalities generated by unilateral labyrinthine lesion. Moreover, in animals that have recuperated from the balyrinthine lesion, 3-acetylpyridine produces a reversal of the symptoms within 2 hours of administration. These results indicate that the integrity of the olivo-cerebellar system is necessary for the acquisition and retention of this form of motor learning, but that the cerebellum itself is not the seat of such learning.

Animals↗

Diversity of mossy fibres in the cerebellar cortex in relation to different afferent systems: an experimental electron microscopic study in the cat.

The evolution of the terminal degeneration has been compared in two systems of mossy fibres: the spinocerebellar and the pontocerebellar projections. The two systems exhibit both dense and clear types of terminal degeneration. However, there are important differences between the evolutive processes of terminal degeneration in the two systems: (i) the time course of the degenerating process is much faster for spinocerebellar than for pontocerebellar rosettes, and (ii) the glial phagocytic process accompanying the dense type of degeneration is different for the two systems. Spinocerebellar rosettes are generally removed from their glomerular central position by reactive glia, leaving fragments of the presynaptic membrane attached to their postsynaptic partner. This feature is exceptional for pontocerebellar rosettes which, in the course of their glial engulfment, leave free the postsynaptic differentiation of their former target granule cell dendrites. These differences of terminal degenerative processes have been reconciled with optical microscope observations by Brodal and Drablos1 of morphological differences between the rosettes of two different fibre systems.

Afferent Pathways↗

Anatomical, physiological and biochemical studies of the cerebellum from mutant mice. II. Morphological study of cerebellar cortical neurons and circuits in the weaver mouse.

The vermis of the homozygous weaver mice has been examined with Golgi and electron microscopic techniques. In addition to the findings already reported by previous authors 12, 29, new cytological features concerning all the cerebellar neuronal types and the synaptic reorganization of the cerebellar circuitry are described. As in other agranular cerebella, Purkinje cells do not develop spiny branchlets and have a randomly oriented dendritic tree. By contrast, their thick dendrites are studded with spines; according to their size and shape these were classified into: (a) small stubby spines which are the normal postsynaptic targets for climbing fibers; (b) tertiary-like spines, most of which are free of axonal contacts; (c) dolichoderus spines; (d) branching spines; and (e) hypertrophic spines. The last 3 types do not exist in normal cerebellum. Postsynaptic-like differentiations are frequently undercoating the smooth surface of the Purkinje dendrites. As it happens in the case of the free spines, free postsynaptic sites in the shafts of the dendrites develop an extracellular material similar to the material present in synaptic clefts. Basket and stellate cells also develop postsynaptic-like differentiations undercoating the somatic and dendritic plasma membranes. These free postsynaptic sites can reach a gigantic size, being longer than 3 mum in length. The rare postmigrative granule cells which persist in wv exhibit claw-endings not only at the dendritc terminal segments, but at the proximal dendritic stems as well. Some of these granule cells, besides having fully achieved migration, undergo a degenerative process indicating that they are probably directly affected by the mutation. Concerning the cerebellar circuitry, and despite the great number of free postsynaptic sites, the large majority of the synaptic contacts keep their specificity. However, some quantitative variations have been disclosed. The surface density of climbing varicosities is increased, whereas that of mossy rosettes is decreased. Stellate and basket fibers are present and their density also decreased. Furthermore, the pinceau formation around the initial segment of the Purkinje cell axon is missing. In addition to all normal synapt iccontacts (with the exception of the'parallel fiber-omnicellularsystem') present in weaver, heterologous synapses have also been encountered, mainly concerning the Purkinje dendritic spines, which can be contacted by mossy rosettes, granule cell bodies and/or dendrites. Morphological signs of partial innervation of the free postsynaptic sites on the smooth surface of Purknje dendrites and the perikarya and dendrites of interneurons have also been observed. These results confirm the existence of synaptic remodeling in wv cerebellum

Animals↗

Morphological correlates of electrotonic coupling in the magnocellular mesencephalic nucleus of the weakly electric fish Gymnotus carapo.

The magnocellular mesencephalic nucleus (MMN) of Gymnotus carapo was studied by electron microscopy. This particular nucleus, characteristic of weakly electric fish, contains two principal classes of neuron. (1) Large neurons (25-35 mum): these are rounded unipolar cells, with the perikaryon partially covered by a sheath of compact myelin. The axon leaves the neuron as a short thick unmyelinated process not resembling the initial segment of multipolar neurons. The axon branches profusely and becomes myelinated very close to its origin. The perikaryal surface not covered by the myelin sheath receives abundant club endings. The synaptic interface between club endings and large neurons is characterized by alternating gap junctions and attachment plaques. In addition, at the periphery of the club endings, "active" zones are generally present, and this synapse is therefore a "mixed" synapse. (2) Small neurons (5-12 mum): these are uni- or bipolar cells, scattered throughout the nucleus, and occasionally, grouped in small clusters. Gap junctions were not observed between neuronal perikarya in such clusters. The synaptic investment of small neurons is formed by long cup endings which almost completely encircle the perikarya. The synaptic interface between cup endings and the perikarya of small neurons is characterized by large areas of gap junctions. A single cup ending establishing gap junctions with two small neurons within the plane of the section was frequently observed and this arrangement provides a morphological basis for electrotonic coupling between small neurons by way of presynaptic fibres. In the neuropil of the MMN, there are abundant synaptic islands constituted by a large axon terminal in synaptic contact with small unidentified profiles; both synaptic elements are surrounded by numerous thin glial lamellae. At the synaptic interface, in the islands, both gap junctions and "active" zones are present. The synaptic islands must also be considered as "mixed" synapses. The morphological results presented here correlate with electrophysiological data (Szabo et al., 1975). The very short delay (0.8-1.3 ms) of the MMS response to the fish's own electric organ discharge can only be explained by the existence of electrotonic transmission along the neuronal chain of the electrosensory pathway. The presence of gap junctions between club endings and large neurons provides a morphological basis for electrotonic transmission at the mesencephalic level of the electrosensory pathway.

Animals↗