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Projections from the intracerebellar nuclei to the ventral midbrain tegmentum in the rat.

The present study was undertaken to provide anatomical evidence, in the rat, for a direct projection from the cerebellum towards structures, other than the red nucleus, which belong to the ventral midbrain tegmentum, by using the retrograde as well as the anterograde horseradish peroxidase transport method. Following unilateral injection in the ventral midbrain tegmentum of horseradish peroxidase, free or conjugated to wheat germ agglutinin, sparing the red nucleus, retrogradely labeled neurons were found in the contralateral cerebellar lateral nucleus and, at lower density, in the interpositus nucleus. No labeled neurons were found in the fastigial nucleus of either side. Anterogradely labeled axons from lectin coupled horseradish peroxidase injection sites in the lateral and interpositus nuclei reached the contralateral ventral midbrain tegmentum. Terminal labeling was observed in the entire red nucleus as well as in the lateral division of the ventral tegmental area of Tsai, in the dorsal region of the substantia nigra pars compacta, and in the medial part of the retrorubral field. No terminal labeling was found in the caudal linear nucleus, interfascicular nucleus, peripeduncular nucleus, rostral linear nucleus of the raphe, substantia nigra pars lateralis and the substantia nigra pars reticulata. Terminal labeling was also not observed in the ventral midbrain tegmentum following horseradish peroxidase injection in lateral and interpositus nuclei of rats pretreated with kainic acid. In conclusion, it is noteworthy that, besides the red nucleus, the sole structures of ventral midbrain tegmentum receiving cerebellar efferents are those with a higher density of dopaminergic cells.

Animals↗

The role of the ventrolateral nucleus of the thalamus in the switching of descending influences to motor activity in the rat.

Studies on rats showed that the facilitating influence of preliminary transection of the rubrospinal tract on recovery of motor activity and operant reflexes disrupted by lesioning of the red nucleus was more apparent when lesioning was chemical than when lesioning was electrolytic. This is due to the survival of cerebellothalamic fibers to the ventrolateral nucleus of the thalamus after chemical lesioning of the red nucleus with quinolinic acid. It was also shown that preliminary lesioning of the ventrolateral thalamic nucleus strongly hindered the switching of motor activity under the control of the corticospinal tract in rats subjected to section of the rubrospinal tract and lesioning of the red nucleus.

Animals↗

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.

Animals↗

The rubrospinal and central tegmental tracts in man.

Ten cases are presented which illustrate aspects of the anatomy of the rubrospinal and central tegmental tracts in man. It is concluded that the number of large fibres arising from the magnocellular part of the red nucleus and constituting the classical rubrospinal tract is small and that only a few fibres project into the spinal cord; these cannot usually be traced caudal to the upper cervical segments. There is a very large number of rubro-olivary fibres arising from the parvocellular part of the red nucleus, which run in the central tegmental tract. This tract also contains descending fibres that do not originate in the red nucleus and fibres that do not terminate in the olive. The literature on the rubrospinal tract and the rubro-olivary component of the central tegmental tract in primates in reviewed. Comparative anatomical studies are also briefly reviewed; they accord with the findings reported here for man.

Adult↗

The development of rubrospinal, cerebellorubral, and corticorubral connections in the North American opossum. Evidence for asynchronism.

We have employed axonal transport and degeneration techniques to study the development of major rubral connections in the North American opossum. Opposums were chosen for study because they are born 12 d after conception and have a protracted postnatal development. Our results suggest that: The red nucleus innervates the spinal cord early in development, well before the somatic motor-sensory cortex (Cabana and Martin, 1984); the red nucleus projects to the spinal cord before it receives substantial projections from the cerebellum or cerebral cortex; and projections from the cerebellum reach the red nucleus significantly earlier than those from the cerebral cortex.

Animals↗

[The role of ventrolateral thalamic nucleus in switching of the descending influence over to the rat motor activity].

Facilitated influence of preliminary transection of the rat rubrospinal tract on motor activity and instrumental reflexes recovering after lesion of the red nucleus was more obvious after a chemical lesion rather than the electrolytic lesion. This seems to be due to remaining cerebello-thalamic fibres after a chemical lesion of the red nucleus. A preliminary destruction of the ventrolateral thalamic nucleus was shown to complicate switching of the motor activity in the rats with transected rubrospinal tract and lesioned red nucleus.

Animals↗

Immunocytochemical demonstration of GABAergic synapses on identified rubrospinal neurons.

GABAergic synapses on rubrospinal neurons were demonstrated with immunocytochemistry combined with intracellular injection of horseradish peroxidase. Sections containing red nucleus neurons were processed for glutamic acid decarboxylase (GAD) immunohistochemistry. GAD-immunoreactive synaptic endings formed synaptic contacts with somata and dendrites of red nucleus neurons and identified rubrospinal neurons. Our observation provides further evidence that GABA acts as an inhibitory transmitter mediating cortically evoked inhibitory postsynaptic potentials in red nucleus neurons.

Animals↗

Spinal projections from the mesencephalon in the toad.

Mesencephalic cell groups projecting to the spinal cord have been identified by means of the retrograde axonal transport of the enzyme horseradish peroxidase (HRP). The injections were made either in the cervical or lumbar enlargements of the toad spinal cord. Following injections in the cervical cord, labeled cells are located in the isthmus region, in the ipsilateral laminated nucleus posteroventralis tegmenti mesencephali (Potter). At more rostral levels the labeled cells are in the nucleus of the fasciculus longitudinalis medialis, in the nucleus interstitialis of the fasciculus longitudinalis medialis, in the contralateral red nucleus, in lamina six of the contralateral optic tectum, bilaterally in the nucleus of the posterior commissure and in the mesencephalic nucleus in the Vth nerve. Injections in the lumbar cord label neurons of the nucleus posteroventralis tegmenti mesencephali (Potter) and nucleus interstitialis of the fasciculus longitudinalis medialis. Nuclei that had not been previously identified in anurans but which were labeled after HRP spinal injections (i.e., the nucleus interstitialis of the fasciculus longitudinalis medialis, the nucleus of the posterior commissure and the red nucleus) have been delimited in normal material in Nissl-stained transverse sections. The spinal pathways from the mesencephalon can be classified into four projections: reticulospinal, rubrospinal, tectospinal and trigeminospinal. A comparison of these descending fiber systems with homologous pathways in other vertebrate species has been made.

Animals↗

Target cells of rubrospinal tract fibres within the lumbar spinal cord.

This short review concerns the problem of how the red nucleus contributes to the initiation and execution of movements. However, it deals with only one aspect of this problem, and focuses on the question of which intrinsic spinal interneuronal networks are used by neurones in the red nucleus to induce movements. The evidence is reviewed that neurones in the red nucleus have access to interneurones with a great variety of functions, excitatory as well as inhibitory. These interneurones are interposed in a number of different spinal reflex pathways, and include both the first and last order interneurones of these pathways. Through them different sets of motoneurones may be affected. All types of interneurones involved are also used by other descending systems, e.g. by cortico- and/or reticulospinal systems, and integrate descending commands with information from various peripheral receptors.

Animals↗

Chromosome fibers from an interphase nucleus.

Red blood cells of the newt, Triturus, were spread on a water surface and picked up with carbon-coated grids for examination in the electron microscope. The identifiable nuclear material consists entirely of long fibers having a diameter of approximately 400 to 600 A. Similar fibers have been seen in human and grasshopper chromosomes prepared in the same manner.

Cell Nucleus↗

Compensatory sprouting and impulse rerouting after unilateral pyramidal tract lesion in neonatal rats.

After lesions of the developing mammalian CNS, structural plasticity and functional recovery are much more pronounced than in the mature CNS. We investigated the anatomical reorganization of the corticofugal projections rostral to a unilateral lesion of the corticospinal tract at the level of the medullary pyramid (pyramidotomy) and the contribution of this reorganization and other descending systems to functional recovery. Two-day-old (P2) and adult rats underwent a unilateral pyramidotomy. Three months later the corticofugal projections to the red nucleus and the pons were analyzed; a relatively large number of corticorubral and corticopontine fibers from the lesioned side had crossed the midline and established an additional contralateral innervation of the red nucleus and the pons. Such anatomical changes were not seen after adult lesions. Intracortical microstimulation of the primary motor cortex with EMG recordings of the elbow flexor muscles were used to investigate possible new functional connections from the motor cortex of the pyramidotomy side to the periphery. In rats lesioned as adults, stimulation of the motor cortex ipsilateral to the pyramidotomy never elicited EMG activity. In contrast, in P2 lesioned rats bilateral forelimb EMGs were found. EMG latencies were comparable for the ipsilateral and contralateral responses but were significantly longer than in unlesioned animals. Transient inactivation of both red nuclei with the GABA receptor agonist muscimol led to a complete loss of these bilateral movements. Movements and EMGs reappeared after wash-out of the drug. These results suggest an important role of the red nucleus in the reconnection of the cortex to the periphery after pyramidotomy.

Afferent Pathways↗

Pentobarbital-like electroencephalographic rubral rhythm induced by ketamine in rabbits.

1. The effects caused by the dissociative anaesthetic drugs (PCP, KT), the sigmaopiates (SKF 10.047, cyclazocine), and the mixed excitatory amino acid antagonist CCP on the electrical activity of the red nucleus in rabbits were compared with PB. 2. Ketamine (10 mg/kg, i.v.) induced the appearance of a pentobarbital-like EEG synusoidal rhythm characterized by an increase in amplitude and a decrease in frequency of the basal electrical activity at the red nucleus level. 3. Both pentobarbital and ketamine induced rhythms were blocked by the GABA-antagonist pentylenetetrazol at the subconvulsant dose of 10 mg/kg, i.v. 4. Phencyclidine, SKF 10.047, cyclazocine, and the mixed excitatory amino acid antagonist CCP failed to affect the basal electrical activity of the red nucleus. 5. These data indicate an interaction of ketamine on the GABA neurotransmission at the level of cerebello-rubral pathways which the other PCP/sigma opiates did not present.

Animals↗

Electron microscopic study of the rubrocerebellar projection in the cat.

Rubral neurons sending axons to the cerebellar anterior interpositus nucleus (AIN) in the cat were identified light microscopically by labeling them with horseradish peroxidase (HRP). The synaptic organization of these rubral neurons and of their afferents from the cerebral motor cortex and the AIN was also analyzed electron microscopically by combined anterograde degeneration and retrograde HRP-labeling techniques. In the light microscopic study, either HRP or a mixture of HRP and kainic acid was injected into the AIN. Both of the injections resulted in retrograde labeling of rubrocerebellar projection neurons in the red nucleus on the contralateral side. The labeled neurons were distributed throughout the rostrocaudal extent of the red nucleus: some lay in clusters. Most labeled neurons were small to medium-sized, although some were large. The injection of HRP into the AIN also resulted in anterograde labeling of cerebellorubral projection fibers terminating in a wider area of the red nucleus on the contralateral side of the injection, whereas the injection of a mixture of HRP and kainic acid showed no anterograde labeling of fibers or terminals. In one set of electron microscopic observations, HRP injections into the AIN were combined with ablation of the motor cortex. Degenerating axon terminals were occasionally found to synapse with both dendrites and neuronal somata labeled with HRP retrogradely. In another set of electron microscopic observations, a mixture of HRP and kainic acid was injected into the AIN in order to label rubrocerebellar projection neurons retrogradely and to bring about degeneration in the cerebellorubral projection fibers anterogradely. Abundant degenerating axon terminals were observed to make axosomatic synaptic contacts with rubral neurons labeled with HRP retrogradely and also with unlabeled rubral neurons. These results indicate that cerebrorubrocerebellar and rubrocerebellorubral monosynaptic circuitries exist which constitute one of the cerebrocerebellar linkages, as well as those linkages via the inferior olivary complex and the pontine nuclei.

Animals↗

The development of selected rubral connections in the North American opossum.

We have employed axonal transport and degeneration techniques to study the development of selected rubral connections in the North American opossum. Opossums were chosen for study because they are born in an immature state, 12 days after conception, and have a lengthy postnatal development. The results of our studies suggest that: (1) the red nucleus innervates the spinal cord early in development, but not as early as some areas of the brainstem; (2) rubrospinal development occurs postnatally in the opossum; (3) rubrospinal axons do not grow synchronously into the spinal cord, but are added over time; (4) rubrospinal development follows rough rostral to caudal and lateral to medial gradients; (5) the red nucleus is innervated by the cerebellum well before it receives projections from the cerebral cortex; and (6) cortical axons do not grow into the red nucleus until after rubrospinal axons have reached most of their adult targets.

Afferent Pathways↗

Response of rubromotoneuronal cells identified by spike-triggered averaging of EMG activity in awake monkeys.

Red nucleus neurons were recorded in awake monkeys during alternating ramp-and-hold wrist movements into flexion and extension position zones. Spike-triggered averages (STAs) of rectified EMG activity of wrist flexor and extensor muscles were computed to document effects of single RN cells on the activity of forelimb motoneurons. Some red nucleus cells produced a transient short-latency post-spike facilitation (PSF) of motor unit firing probability, indicative of underlying rubromotoneuronal (RM) connections. We, therefore, termed these RM cells. The discharge of wrist-related red nucleus cells was more strongly correlated with the dynamic than static component of wrist movement.

Animals↗

Direct and indirect "cortico"-rubral and rubro-cerebellar cortical projections in the pigeon.

In birds the red nucleus is the most rostral cell group in the brain having projections to all levels of the spinal cord (Cabot et al., Prog. Brain Res., 57:79-108, 1982), but its sources of afferents are incompletely known. In order to determine these, a series retrograde and anterograde tracing experiments was carried out, largely with cholera toxin B-chain conjugated to horseradish peroxidase. The results show that a sparse and diffuse projection to the red nucleus arises from deep regions of the hyperstriatum accessorium (HA) of the anterior Wulst, and that a much more dense projection arises from the caudal part of the nucleus principalis precommissuralis and the medial part of the medial spiriform nucleus (SpMm). These last two sources were themselves shown to receive a substantial projection from HA of the anterior Wulst. The red nucleus was also shown to project upon the cerebellar cortex of lobule VI, and SpM upon the cerebellar cortex of lobules VI through IX (Karten and Finger, Brain Res., 102:335-338, 1976; Clarke, J. Comp. Neurol., 174:535-552, 1977). Double retrograde labelling experiments with fluorescein and rhodamine labelled latex microspheres injected into the cerebellar cortex and spinal cord showed that the rubrocerebellar cortical neurons are a different population from, although intermixed with, the rubrospinal neurons.

Animals↗

MR detection of brain iron.

PURPOSE: To provide further quantitative studies concerning the relationship with age between regional brain iron and T2 shortening. METHODS: a) Quantitative T2 calculations of eight anatomic regions (red nucleus, substantia nigra, dentate nucleus, corpus callosum, caudate, putamen, temporal lobe white matter, and frontal lobe white matter) from T2-weighted spin-echo images were performed in 60 patients aged newborn to 35 years. b) Quantitative brain iron concentrations were obtained in six of the eight anatomic regions (red nucleus, substantia nigra, dentate nucleus, corpus callosum, cauda, and putamen) using 13 autopsied brains (newborn to 78 years). Brain tissue from these six regions was digested with 0.6 N HCl-2.5% wt/vol KMnO4 for 2 hours at 60 degrees C. After centrifugation, 0.1 mL of an iron-chelating reagent (2 mol/L ascorbic acid, 5 mol/L ammonium acetate, 6.5 nmol/L ferrozine, 13.1 mmol/L neocuprine) was added and the absorbance was measured at 562 nm/L and compared with a standard curve with ferric chloride. c) The in vivo iron concentrations in tissue that were obtained were reproduced in four test tube phantom studies with ferric ammonium sulfate or ferrous ammonium sulfate dissolved in either deionized water or 5% agarose. T2 calculations of the phantoms were made with a single-section multiple repetition time, multiple echo time acquisition. RESULTS: a) Clinical T2 calculations--all eight anatomic regions showed a decrease with age in T2 value, beginning shortly after birth. During the first three decades, the T2 shortening was most significant in the region of substantia nigra. b) Quantitative brain iron--five anatomic regions but not the corpus callosum demonstrated an age-related increase in brain iron (1449.6 nmol/g for the red nucleus versus 261.8 nmol/g for the corpus callosum). c) T2 effect of iron in vitro--both the ferric and ferrous iron phantoms showed a decreased T2 value in the in vivo concentration range of iron obtained from the postmortem studies. The T2 shortening was most marked for the ferric phantoms. CONCLUSION: There is an age-related accumulation of iron in five regions of the brain, correlating with an associated decrease in T2 value that can be demonstrated in iron phantoms. Brain iron appears to contribute to the progressive decrease of T2 signal that occurs with aging.

Adolescent↗

Sites of action of segmental and descending control of transmission on pathways mediating PAD of Ia- and Ib-afferent fibers in cat spinal cord.

The present series of investigations was aimed to disclose the possible sites of action of excitatory and inhibitory inputs on tho-interneuron pathway mediating the primary afferent depolarization (PAD) of group I afferents of extensor muscles in the cat spinal cord. To this end we compared the effects produced by stimulation of segmental and descending pathways on the PAD generated either by stimulation of group I fibers of flexor muscles or by intraspinal microstimulation. It was assumed that under the appropriate conditions the PAD produced by intraspinal microstimulation results from the activation of the last-order interneurons in the PAD pathway and may, therefore, allow detection pathway. The PAD of single group I afferent fibers was determined in barbiturate-anesthetized preparations by measuring the test stimulus current required to maintain a constant probability of antidromic firing. This was achieved by means of a feedback system that continuously adjusted the test stimulus current to the required values. The PAD of individual group Ia gastrocnemius soleus (GS) fibers that is produced by activation of the low-threshold afferents of the posterior biceps and semitendinosus nerve was found to be inhibited by conditioning stimulation of the relatively low-threshold cutaneous fibers and also by stimulation of supraspinal structures such as the ipsilateral brain stem reticular formation, the contralateral red nucleus, and the contralateral pyramidal tract. In contrast, the PAD of group Ia fibers produced by microstimulation applied in the intermediate nucleus could be inhibited only by stimulation of the brain stem reticular formation but not by stimulation of the other descending inputs presently tested or by stimulation of cutaneous nerves. PAD of group Ia fibers was produced also by microstimulation applied within the motor nucleus. However, in most fibers the resulting PAD could not be inhibited either by stimulation of the brain stem reticular formation, the red nucleus, the pyramidal tract, or cutaneous nerves. Stimulation of cutaneous and of flexor muscle nerves of the brain stem reticular formation, the red nucleus, and the pyramidal tract all produced PAD of the group Ib GS fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗