[Structural basis for the inhibitory function of the parietal cortex efferent systems].

Relative quantitative distribution of all the associative and descending efferent fibers and the ultrastructural organization of the terminals of the parietal cortex areas 5 and 7 in the caudate (NC) and red nucleus (NR) in the cat were analyzed after a local, pointed destruction of the cortex of these areas. The maximal numbers of the associative fibers were found to project to the fundus areas of the motor cortex and to the area of Clare-Bishop; moderate projections were detected to the areas 31, 19 and single degenerating fibers were registered in the areas 1,2, 3a, 3b, 30, and 23. The descending efferents were maximally projecting to NC, NR, reticular nuclei of the thalamus, midbrain, and pons, in all of which, according to the immunocytochemical studies, GABA-ergic terminals are prevalent. On the basis on the electron microscopical studies, it was suggested that the influence of the parietal cortex is mediated by the axo-spinal synapses of the medium shortaxonal spiny cells of the dorsolateral part of NC caput and by the axo-dendritic synapses of Golgi II cells of the parvocellular part of NR. On the basis of the maximal involvement of the fundus areas of the motor cortex, as well as of the inhibitory subcortical (NC) and stem nuclei (NR, reticular nuclei of the thalamus, midbrain, and nuclei pontis), it is suggested that these structures serve as the morphological substrates for the realization of the inhibitory, integrative function of the parietal cortex.

[Quantitative analysis of the distribution of the cortical motor representation of forelimb and hindlimb areas in cat nucleus ruber].

Quantitative analysis of the corticorubral fibers distribution was performed after point electrolytic destruction of lateral and medial borders of posterior sigmoid gyrus, which are the motor representations of the forelimb and hindlimb areas in the nucleus ruber of the cat. It was shown that the cortical representation area of the forelimbs projected to the whole rostro - caudal extension of the nucleus ruber. Number of efferent fibers terminating in rostral border of nucleus ruber, was almost two times grater than that in the caudal third. The efferent fibers of the hindlimb area were found not to project to the rostral two thirds of nucleus ruber, and were found to terminate only in its caudal third. The quantity of these projecting corticorubral fibers is equal to that projecting from cortical representation of the forelimbs to caudal third of nucleus ruber. The significant (almost two-fold) prevalence of the number of the fibers projecting from cortical representation of the forelimbs over that projecting from cortical representation of the hindlimbs, found in this study, may suggest greater functional significance of corticorubral connections for the motor reactions realized by the forelimbs.

Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function.

Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons.

Connections of the superior vestibular nucleus with the oculomotor and red nuclei in the rat: an electron microscopic study.

Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into the individual vestibular nuclei of the rat to study their efferent connections. One of the major differences between the connections of these nuclei was found at the level of the mesencephalon: the eye-moving cranial nerve nuclei received the densest projection from the superior vestibular nucleus (SVN). In the present electron microscopic study, we have found that terminals of SVN origin established symmetric synaptic contacts in the oculomotor nucleus. More than two-thirds of PHA-L-labeled boutons terminated on dendrites, the rest of them established axosomatic contacts. Most of the labeled terminals were GABA-positive, supporting the results of previous physiological experiments, which showed inhibitory effects. In the mesencephalon, the other termination area was found in the red nucleus. The PHA-L-labeled boutons of SVN origin were in close contact with the perikarya and proximal dendrites of the magnocellular part of the red nucleus. The types of synaptic contacts and distribution of terminals of SVN origin were similar to those found in the oculomotor nucleus. Our results indicate that the SVN can modify the activity of the cerebellorubral and corticorubral pathways, exerting inhibitory action on the neurons of the red nucleus.

Ultrastructure of axonal reaction in red nucleus of cat.

Described here are ultrastructural changes in neurons of feline red nucleus exhibiting axon reaction after unilateral rubropsinal tratotomy at the C-2 level and surviving 2 to 65 days. Ultrastructural alterations included neurofilamentous hyperplasia; proliferation of smooth ER; temporary disappearance of organized granular ER with partial substitution by haphazardly arranged, broad cisternal profiles; loss of rosette ribosomes and occurrence of single ribonucleoprotein granules or an intercisternal amorphous density; increased numbers of subsurface cisterns and allied structures, often disposed in stacks; vesiculation and vacuolation of Golgi cisternae; prevalence of autophagic bodies derived in part from Golgi complexes; probable mitochondrial hyperplasia and various qualitative changes in these organelles; an increase in lipofuscin. Dendritic changes paralleled those of perikarya save that proliferation of subsurface cisterns and autophagic bodies was absent. Abnormalities of myelinated axons and boutons occurred and may have originated from retrograde degeneration of cortical neurons induced by lateral funiculotomy. Some perikarya were devoid of axosomatic boutons. Ultrastructural changes varied with the length of postoperative survival and were, at least partly, reversible. Chromatolysis was detectable light microscopically before ultrastructural abnormality appeared. The bearing of transneuronal mechanisms on axon reaction of central neurons and the protective effect of section of axons beyond the site of origin of collaterals are discussed.

Red nucleus of Macaca fascicularis: an electron microscopic study of its synaptic organization.

The parvicellular and magnocellular divisions of the red nucleus of the old world monkey, Macaca fascicularis, were analyzed at an electron microscopic level to examine the morphology of the synaptic profiles terminating on rubral neurons and to categorize them by their individual characteristics. The parvicellular division, or anterior two-thirds of the nucleus, is composed of small (10-15 microns) and medium-size (20-30 microns) cells, which are uniformly distributed with high packing density throughout this portion of the nucleus. These cells have invaginated nuclei and are often indented by blood vessels and glial cell somata (satellite cells) that lie in close proximity. The magnocellular portion, occupying the caudal one-third of the nucleus, is composed of an additional population of large cells, ranging from 50-90 microns in diameter, which often contain prominent lipofuscin granules and are frequently indented by blood vessels. Satellite glial cells are not a prominent feature in the magnocellularis portion of the nucleus. The large cells are separated one from the other by fields of myelinated axons either coursing through the nucleus or projecting to and from the nucleus itself. Although the divisions of the nucleus in the Macaca fascicularis are spatially distinct, each possesses a morphological similarity in regard to the categories of synaptic profiles seen at the electron microscopic level. These synaptic profiles are classified as follows: large terminals containing numerous, predominantly rounded vesicles (LR), which can often be seen to form the central profile in a synaptic glomerular arrangement; terminals of similar size with predominantly rounded vesicles but with a pale axoplasmic matrix (LRP); small profiles with rounded vesicles (SR); profiles containing granular dense-cored vesicles (DCV); profiles with numerous flattened vesicles (F); profiles containing pleomorphic vesicles (PL), some of which can be interpreted as presynaptic dendrites (PSD) because they are seen to be postsynaptic and contain ribosomes; and profiles with rounded synaptic vesicles, which are associated with subsynaptic Taxi bodies (T). Most of the various synaptic profile types were found to have similar distributions on the dendritic arbors of rubral neurons in both divisions of the nucleus. However, the LRP-type terminal predominates on the cell bodies and proximal dendrites of the large neurons in magnocellularis. Unlike other regions in the nervous system, F type terminals are rarely seen to contact neuronal somata. This study provides a basis for future experimental studies of afferents to the nucleus in this species.(ABSTRACT TRUNCATED AT 400 WORDS)

An ultrastructural study of the red nucleus in the rat.

The red nuclei of 14 adult male rats of the Wistar strain were prepared for electron microscopic study following perfusion with a mixture of aldehydes, Neurons of four size categories were identified in 1 mu Epon sections and their ultrastructural characteristics were studied in adjacent thin sections. Giant (greater than 40 mu) and large (26-40 mu) neurons are distinguished primarily by size and possess similar ultrastructural features: extensive areas of rough endoplasmic reticulum (RER), a prominent perinuclear Golgi complex, numerous mitochondria and pigment granules and a large, ovoid nucleus which occasionally contains intranuclear rodlets. Medium size neurons (20-25 mu) have less extensive, poorly organized RER and randomly distributed Golgi complexes. The nuclear envelopes of these cells frequently show multiple invaginations and continuity with the RER cisternae. In small neurons (less than 20 mu) the RER occurs as single or anastomosing strands whi le golgi complexes and pigment granules are few. In both medium size and small neurons, aggregates of condensed chromatin are adherent to the inner nuclear membrane. Three main types of synaptic terminals may be distinguished in the red nucleus: (1) small terminals with flattened vesicles and symmetrical densities (F terminals), (2) small terminals with rounded vesicles and asymmetrical densities (RS terminals), and (3) large (10-15 mu) asymmetrical, rounded vesicle terminals which form multiple contacts along their length (RL terminals). The small neurons receive both F and RS terminals on their dendrites and infrequently on their cell somas. The large and giant neurons receive F, RS and RL terminals on their somas and proximal dendrites and F and RS terminals on their distal dendrites. The somas and dendrites of medium size neurons receive both F and RS terminals but RL terminals do not lie in relation to them. Spine contacts are common throughout the nucleus and occur on both somas and dendrites.

An HRP-TMB ultrastructural study of rubral afferents in the rat.

The projections from the deep cerebellar nuclei and the sensorimotor cortex to the red nucleus were studied in the rat using anterograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA). The anterogradely transported HRP-WGA was visualized ultrastructurally by using a modification of the tetramethylbenzidine (TMB) histochemical technique of Carson and Mesulam ('82). Following injection of HRP-WGA into the sensorimotor cortex, ultrastructural examination of anterograde labeling in the ipsilateral red nucleus revealed labeled synaptic terminals located on small-diameter dendrites of the parvocellular region. These terminals made asymmetrical contacts and contained round vesicles. HRP-WGA placement in the nucleus lateralis resulted in anterograde labeling of synaptic terminals which made asymmetrical contacts with small- to medium-sized dendrites of the parvocellular red nucleus. Similar placements in the nucleus interpositus gave rise to anterograde labeling of synaptic terminals which made asymmetrical contacts with somata and proximal dendrites of magnocellular neurons. In addition, retrograde labeling of magnocellular neurons was also observed following HRP-WGA placements in the nucleus interpositus. Anterogradely labeled interpositorubral synaptic terminals were located on retrogradely labeled rubrocerebellar neurons. The rat red nucleus thus receives topographically organized afferents which are characterized by their specificity in location at the cellular level.

Ultrastructural study of remodeled rubral afferents following neonatal lesions in the rat.

Following neonatal hemicerebellectomy, an aberrant ipsilateral cerebellorubral projection develops that maintains the topographic specificity of the normal contralateral projection. Similarly, neonatal lesions of the sensorimotor cortex lead to the appearance of an aberrant contralateral corticorubral projection that mirrors the topographic specificity of the normal ipsilateral input. The specificity of synaptic localization in these aberrant projections was studied by use of ultrastructural visualization of anterogradely transported HRP-WGA. Following neonatal ablations, adults received HRP-WGA injections in the unablated deep cerebellar nuclei or sensorimotor cortex. After 48 hours, animals were sacrificed and processed for ultrastructural localization of anterogradely transported HRP-WGA. In hemicerebellectomized animals, both the contralateral and ipsilateral interpositorubral projections terminated on the somatic and proximal dendritic membrane of magnocellular neurons. Some of these labeled synaptic terminals were located on somatic and dendritic spines. Following HRP-WGA injection in the unablated nucleus lateralis, anterogradely labeled synaptic terminals were located bilaterally on small- to medium-sized dendrites of parvicellular neurons. Injection of HRP-WGA in the remaining sensorimotor cortex of animals that had undergone neonatal unilateral ablation of the sensorimotor cortex resulted in labeled corticorubral synaptic terminals that contacted distal dendrites of ipsilateral and contralateral parvicellular neurons. These results demonstrate that, following neonatal deafferentation of the rat red nucleus, the topographic specificity of the aberrant rubral afferents is accompanied by a specificity of synaptic localization on discrete membrane areas of rubral neurons.

Corticorubral synaptic organization in Macaca fascicularis: a study utilizing degeneration, anterograde transport of WGA-HRP, and combined immuno-GABA-gold technique and computer-assisted reconstruction.

The macaque red nucleus receives afferents from two major sources, the cerebral cortex and the deep cerebellar nuclei. Approximately 90% of the corticorubral afferent axons project to pars parvicellularis of the red nucleus, the neurons of which transmit information to the cerebellum by way of the inferior olivary nucleus. The remaining 10% project to pars magnocellularis of the red nucleus, the major projection of which is to the spinal cord. In this study, corticorubral terminations labeled following lesions or injections of wheatgerm agglutinin conjugated to horseradish-peroxidase into the topographically defined hand area of the primary motor cortex were quantitatively studied via electron microscopy. Cortical afferent terminals within pars parvicellularis and pars magnocellularis synapse upon all regions of the dendritic arbors of rubral projection neurons. However, the majority of these labeled afferents synapse upon thin-diameter shafts or presumed spinous processes of rubral distal dendrites as well as upon vesicle-containing profiles of presynaptic dendrites of local circuit interneurons that are gamma-aminobutyric acid-immunoreactive, as identified by postembedding immunohistochemistry. Synaptic contacts formed by the labeled cortical terminal were large in width and extended through several serial sections. Synaptic contacts formed by the presynaptic dendritic profiles, on the other hand, were more punctate and could be seen in only one or two serial sections. These latter synaptic interactions probably provide a modification of the effects of cortical input to rubral projection neurons as suggested by previous physiological studies that indicated the dominance of cortical input onto distal dendrites as well as involvement with inhibitory circuits. An example of the complexities of these synaptic interactions is further demonstrated by a three-dimensional computer reconstruction. This quantitative study of corticorubral afferents in the macaque monkey provides insight into the interactions of cerebral cortical afferents with rubral projection neurons and their relationship with local circuit inhibitory interneurons to elucidate the role played by the cortex in the activation of rubral neurons.

Light and electron microscopic study of corticorubral synapses in adult cat: evidence for extensive synaptic remodeling during postnatal development.

Spine-like dendritic protrusions (SLDPs) emanating from developing dendrites have been proposed to play an important role in early synaptogenesis. We previously analyzed synaptic termination sites on soma-dendritic membrane of newborn cats and found that corticorubral (CR) axons form synapses preferentially on SLDPs (Saito et al., 1997). In the present study, we examined CR synapses in adult cats to elucidate the maturation process of CR synapses in relation to SLDPs. Electron microscopic observation of serial thin sections of Phaseolus vulgaris-leucoagglutinin-labeled axons revealed that approximately 60% of CR terminals in adult cats formed synapses on dendritic spines. We also found that CR axons terminate on dendritic spines originating from the intermediate or distal dendrites of rubrospinal cells (more than 200 microm apart from the soma), in contrast to kittens in which CR fibers terminate on SLDPs originating from the proximal dendrites (less than 100 microm apart from the soma) of rubrospinal cells (Saito et al. [1997] J. Neurosci. 17:8792-8803). These results suggest that CR synapses undergo remarkable remodeling after initial termination on SLDP during postnatal development.

Postnatal development of crossed and uncrossed corticorubral projections in kitten: a PHA-L study.

Morphological changes in individual corticorubral fibers and the pattern of crossed and uncrossed corticorubral projections were studied during the postnatal development of cats in order to understand cellular mechanisms for restriction of corticorubral projections with development. The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into restricted areas of the pericruciate cortex in kittens and PHA-L-labeled axons in the red nucleus were examined at postnatal days (PND) 7-73. In accordance with our previous study (Murakami and Higashi, Brain Res. 1988; 447:98-108), a crossed corticorubral projection was observed in addition to the uncrossed one in every experimental animal. During the early period of development (PND 7-8), swellings of irregular shape were observed along the entire course of the axons and they were often interconnected with extremely fine axonal segments. These axons bifurcated only infrequently and often ended as growth cones. These features were common to both uncrossed and crossed corticorubral axons. At later stages of development (PND 28 or later), the total number of swellings decreased and axonal swellings with smooth contours became dominant. A quantitative examination of axonal branches indicated that axons on the ipsilateral side branch occurred more frequently at later stages of development. However, there was no substantial change in branching frequency for the crossed corticorubral fibers during development. In parallel with morphological changes in individual axons, the crossed projection that was initially relatively abundant was reduced during development. Since a PHA-L injection can be confined to a small region of cortex, topographic projections can easily be detected. At PND 7-8 there was no well-defined topographic order in the ipsilateral corticorubral projection. Adult-like topography was first discernible at PND 13. These observations suggest that the unilateral uncrossed corticorubral projection in the adult cat is achieved at least in part by the formation of axonal arbors in the uncrossed projection. This was accompanied by the failure of crossed fibers to form complex arbors. It is possible that a similar mechanism also operates in the formation of topographic maps.

Inhibitory synaptic input to identified rubrospinal neurons in Macaca fascicularis: an electron microscopic study using a combined immuno-GABA-gold technique and the retrograde transport of WGA-HRP.

Rubrospinal neurons of the magnocellular division of the red nucleus of Macaca fascicularis were retrogradely labeled following spinal cord microinjections of wheat germ agglutinin-horseradish peroxidase, as demonstrated by the chromagen tetramethylbenzidine, identifying the mesencephalic cells of origin of this descending motor pathway. The tissue was processed for electron microscopy and subsequently tested on the electron microscope grid for immunoreactivity of gamma aminobutyric acid (GABA) in presumed local circuit neuronal somata, in dendrites, and in axonal terminals. Results demonstrate the presence of retrogradely labeled rubrospinal neurons of medium and large diameters (30-90 microns) and immunoreactive neurons of small size (less than 20 microns in diameter) within the nucleus. In addition, there are substantial numbers of GABAergic, presumably inhibitory, synaptic structures contacting somata and primary, medium, and small sized dendrites, as well as spineheads of rubrospinal neurons. The immunoreactive presynaptic profiles exhibit two different morphological appearances: one axonal and the other dendritic. Axonal terminals contain densely packed pleomorphic to flattened vesicles and form primarily symmetrical synapses with somata and all regions of the dendritic arbor. GABAergic profiles resembling presynaptic dendrites (PSDs) are also present. These profiles possess scattered flattened to pleomorphic synaptic vesicles in a translucent cytoplasm and are often postsynaptic to axonal terminals of unknown origin, or to GABAergic profiles. GABAergic local circuit neurons (LCNs), the neurites of which remain within the confines of the nucleus, appear to be contacted primarily by cortical and cerebellar afferents. These LCNs may or may not possess axons and thus may represent both the source of the GABAergic axonal terminals as well as that of the PSDs. Inhibitory afferents from other sources, such as the mesencephalic reticular formation, may also account for GABAergic terminals involved in this inhibition. We propose that the level of excitability of rubrospinal neurons and their subsequent activation of spinal motor neurons and interneurons is significantly regulated by the local circuit GABAergic inhibitory interneuronal population of the nucleus proper and probably by axons entering the nucleus from an extranuclear source.

GABA nerve endings in the rat red nucleus combined detection with serotonin terminals using dual immunocytochemistry.

Immunocytochemical methods were used to examine the ultrastructural features and cellular interrelationships of GABA and serotonin afferent fibers to the rat red nucleus. GABAergic nerve endings were identified in two ways, either using a pre-embedding immunoperoxidase procedure with an antibody against glutamate decarboxylase, the GABA-synthesizing enzyme, or after post-embedding immunogold labelling with an anti-GABA antibody. With the latter approach, it was possible to simultaneously visualize the GABAergic and serotoninergic innervation of the red nucleus (magnocellular part) in electron microscope preparations. This procedure involved GABA labelling of ultrathin sections obtained from specimens previously immunostained for serotonin using the pre-embedding peroxidase-antiperoxidase technique. The doubly stained sections showed gold and peroxidase markers to be present in two distinct populations of axonal varicosities. Unlike the GABAergic nerve endings, which were found to be profusely distributed throughout the nucleus, the serotonin nerve endings were relatively scarce. They contacted dendrites of large-sized neurons usually endowed with several GABA-gold labelled terminals. Not uncommonly, direct appositions between serotonin and GABA-positive terminals were also encountered. These data provide morphological evidence that red nucleus outputs may be dually regulated by GABAergic and serotoninergic afferents, while suggesting that presynaptic GABA/serotonin interactions might also play a significant part in red nucleus functions.

Subcellular localization of a glutathione-dependent dehydroascorbate reductase within specific rat brain regions.

Recently, we described the occurrence of a dehydroascorbate reductase within the rat CNS. This enzyme regenerates ascorbate after it is oxidized during normal aerobic metabolism. In this work, we describe the neuronal compartmentalization of the enzyme, using transmission electron microscopy of those brain areas in which the enzyme was most densely present when observed under light microscopy. In parallel biochemical studies, we performed immunoblotting and measured the enzyme activity of the cytoplasm and different nuclear fractions. Given the abundance of ascorbate in the caudate-putamen, we focused mostly on the occurrence of dehydroascorbate reductase at the striatal subcellular level. We also studied cerebellar Purkinje cells, hippocampal CA3 pyramidal cells and giant neurons in the magnocellular part of the red nucleus. In addition to neurons, immunolabeling was found in striatal endothelial cells, in the basal membrane of blood vessels and in perivascular astrocytes. In neuronal cytosol, the enzyme was observed in a peri-nuclear position and on the nuclear membrane. In addition, in both the striatum and the cerebellum, we found the enzyme within myelin sheets. Dehydroascorbate reductase was also present in the nucleus of neurons, as further indicated by measuring enzyme activity and by immunoblotting selected nuclear fractions. Immunocytochemical labeling confirmed that the protein was present in isolated pure nuclear fractions. Given the great amount of free radicals which are constantly generated in the CNS, the discovery of a new enzyme with antioxidant properties which translocates into neuronal nuclei appears to be a potential starting point to develop alternative strategies in neuroprotection.

Spinal axonal injury induces brief downregulation of ionotropic glutamate receptors and no stripping of synapses in cord-projection central neurons.

Spinal cord injury often damages the axons of cord-projecting central neurons. To determine whether their excitatory inputs are altered following axonal injury, we used rat rubrospinal neurons as a model and examined their excitatory input following upper cervical axotomy. Anterograde tracing showed that the primary afferents from the cerebellum terminated in a pattern similar to that of control animals. Ultrastructurally, neurons in the injured nucleus were contacted by excitatory synapses of normal appearance, with no sign of glial stripping. Since cerebellar fibers are glutamatergic, we examined the expression of ionotropic receptor subunits GluR1-4 and NR1 for AMPA and NMDA receptors, respectively, in control and injured neurons using immunolabeling methods. In control neurons, GluR2 appeared to be low as compared to GluR1, GluR3, and GluR4, while NR1 labeling was intense. Following unilateral tractotomy, the levels of expression of each subunit in axotomized neurons appeared to be normal, with the exception that they were lower than those of control neurons of the nonlesioned side at 2-6 days postinjury. These findings suggest that axotomized neurons are only temporarily protected from excitotoxicity. This is in sharp contrast to the responses of central neurons that innervate peripheral targets, in which both synaptic stripping and reduction of their ionotropic glutamate receptor subunits persist following axotomy. The absence of an injury-induced trimming of afferents and stripping of synapses and the lack of a persistent downregulation of postsynaptic receptors might enable injured cord-projection neurons to continue to control their supraspinal targets during most of their postinjury survival. Although this may support neurons by providing trophic influences, it nevertheless may subject them to excitotoxicity and ultimately lead to their degenerative fate.

A Golgi study on the red nucleus in man.

The different cell types comprising the human red nucleus (RN) from eight patients without neuronal diseases were investigated using the Golgi-Braitenberg method for long-stored autopsy material. No giant cells were found due to regression of the magnicellular part of the human RN. We found larger (40-50 microns) and smaller (30 microns perikaryon size) medium-sized multipolar neurons with long dendrites, mushroom spines and typical distal dendritic tufts. The larger medium-sized RN neurons had some brush-shaped dendritic end portions which could not be observed in the Golgi studies on various other mammals described in the literature. We additionally found small neurons with a perikaryon size of 15 microns. These cells were thought to be intrinsic neurons similar to those in animal investigations. The neuronal types found in the normal human RN corresponded to those in the parvicellular part of the mammalian RN. Dendritic end brushes, however, are typical only for the human RN.

An electron microscope study of the red nucleus in the cat, with special reference to the quantitative analysis of the axosomatic synapses.

The synaptic organization of the red nucleus in the cat was investigated using the electron microscope and the axosomatic synapses were analyzed quantitatively using serial sections. The bouton covering ratios were found to be 61.5, 16.6 and 6.1% in large, medium-sized and small neurons, respectively. In a vast majority of axosomatic terminals, the synaptic apposition length ranged from 1.2 to 1.4 mum. There were 15-17 axon terminals on each 100 sq. mum of perikaryal surface of a magnocellular neuron. Seventy-four per cent of axosomatic terminals on the magnocellular neuron were filled with spherical vesicles and 22% had flattened vesicles. No clear correlation appears to exist between the shape of synaptic vesicles and the type of the postsynaptic differentiation. Somatic thorns were observed rather frequently on the magnocellular neurons. Axo-dendrodendritic serial synapses were occasionally observed to be present in the red nucleus. All postsynaptic components of these serial synapses contained pleomorphic vesicles. The possible existence of the Golgi type II cells in the red nucleus is discussed in relation to the components consituting the serial synapses.

An electron microscopic study of rubrospinal projections to the lumbar spinal cord of the opossum.

The rubrospinal system is a major suprasegmental input to the important interneuronal pool at the base of the lumbar dorsal horn in the North American opossum. After appropriate lesions, rubral axons and their synaptic terminals were found in electron micrographs of lamina IV, V and VI as well as within the dorsal extreme of lamina VII. Degenerating terminals contact small diameter dendrites in the lateral terminal zone and large dendritic profiles in the medial terminal zone. Correlating these data with the dendritic arborizations of interneurons in Golgi preparations and with existing physiologic studies, it appears that interneurons in the intermediate and medial aspects of lamina V, VI and VII receive rubral input on both their proximal and distal dendrites.

An electron microscopic study of the corticorubral fibers after neonatal deep cerebellar nuclear lesions in albino rats.

After a lesion in the sensorimotor and adjacent cortex in normal adult rats, degenerating terminals showing the dense reaction form asymmetrical contacts with spines, dendrites of various sizes, soma and other axonal terminals. Filamentous degeneration is also present. After neonatal deep cerebellar nuclear lesions involving the dentate nucleus and the adjacent interposed nucleus, the cerebrocorticorubral fibers form similar synaptic contacts with somatic, dendritic and axonal profiles. The incidence of axo-dendritic contacts on spine is reduced, while that of axo-dendritic contacts on small, medium-sized and large dendrites and axo-somatic contacts is increased.