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[Afferent connections of the dorsal sections of the pars magnocellularis in the red nucleus of the cat].

Location of retrogradely labelled neurons in various structures of the central nervous system was studied by microiontophoretic injection of horseradish peroxidase into dorsal sections of the magnocellular part of the cat red nucleus. Projections were revealed from some hypothalamic nuclei, centrum medianum, as well as from nucleus parafascicularis and subthalamic nucleus; from zone incerta, field of Forel, nucleus medialis habenulae; from reticular formation of the pons, medulla oblongata and midbrain, central gray matter, colliculus superior, nucleus interstitialis Cajal; from contralateral red nucleus, nucleus fastigii and facial nucleus; from nucleus vestibularis lateralis (pars dorsalis) and nucleus vestibularis medialis as well as from ventral horn of the spinal cord cervical segments. Connections between substantia nigra and the red nucleus have been studied more accurately. Bilateral trajectories of retrogradely labelled fibre systems are described.

Afferent Pathways↗

Development of the human magnocellular red nucleus: a morphological study.

The development of the human magnocellular red nucleus (RNm) was studied in 20 fetuses at 12-39 weeks of gestation (WG). With microscopic observation on serial sections of the brain, we measured the profile area of a neuronal cell body. At 12WG, several islands of immature cells of the RNm appeared dorsal to the parvocellular red nucleus (RNp). At 16WG, the RNm was detected ventral to the RNp as a cluster of semilunar shape, consisting of basophilic neurons of various sizes. During 18-23WG, the neurons were dispersed dorsal to the RNp. They were isolated or aggregated as small clusters among the myelinated oculomotor nerve roots. Twenty-eight WG onwards, the neurons were widely distributed ventrolateral to the superior cerebellar peduncle and around the caudal pole of the RNp. Measurement of the profile area revealed that the average size of overall neurons increased almost linearly with the gestational age, and that two populations (large and small neurons) were clearly distinguished on the histogram from 33WG onwards. The relative position of the RNm to the RNp may vary among the individuals, especially in earlier fetal stage. This study suggests that the differentiation and maturation of neuronal cytoarchitecture of the RNm may gradually and monotonously progress during the later half of gestation.

Age Factors↗

Responses of red nucleus neurons to antidromic and synaptic activation.

An account is given of the responses of 432 red nucleus (RN) neurons with axons projecting down the spinal cord. Almost half were in an initial series of 18 experiments on anesthetized cats, and the remainder were in a second series of 12 experiments on decerebrate unanesthetized cats. The differences between the two series were of little significance. All recording was from single neurons using extracellular glass microelectrodes that were inserted throught the right superior colliculus and directed to the right red nucleus at a standard orientation. Identification of RN neurons was both by location, checked by subsequent histology, and by antidromic invasion from the spinal cord. The spinal stimulating electrodes were placed in proximity to the left rubrospinal tract at C2 and L2 segmental levels. Axonal conduction velocities were calculated from the latency differential between the L2 and C2 antidromic responses and were usually in the range 60-130 m/s, 97% of all neurons located in the red nucleus had axons projecting to the C2 level, and 37% projected to the L2 level. The responses of 229 RN neurons were observed with stimulation applied to the contralateral (left) interpositus nucleus. In 10 (5%) there were antidromic responses to both interpositus and C2 stimulation, a finding in good agreement with the anatomical description of rare axon collaterals from rubrospinal fibers to the interpositus nucleus. In 209 (91%), there was a clear monosynaptic excitation. The impulse generation was at a latency usually of 1.0-1.8 ms, which a modal value of 1.4 ms. The afferent inputs to RN neurons were provided by stimulation either of predominantly cutaneous nerves in all four limbs or of cutaneous mechanoreceptors of the contralateral forelimb and hindlimb...

Anesthesia, General↗

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.

Animals↗

[Electrical responses of the red nucleus to acoustic stimulation].

Letency of evoked potentials (EPs) recorded in the anesthetized cat's magnocellular part of red nucleus varied from 3.5 to 4.5 msec on binuaural and contralateral stimulations. In ipsilateral stimulation, latency of EPs varied from 6 to 10.5 msec. EPs of the parvocellular part of the red nucleus were of two types: EP of the first type had latency of 4-5 msec, of the second type -6.5-10.5 msec on binaural and contralateral stimulations. In ipsilateral stimulation EP of the first type occurred with latency of 6-9 msec, those of the second -8.5-14 msec. Both latency and amplitude of the responses depended on intensity of the auditory stimulation. Possible ways of transmission of auditory information to red nucleus are discussed.

Animals↗

Neurotransmitter-mediated control of neuronal firing in the red nucleus of the rat: reciprocal modulation between noradrenaline and GABA.

The electrical activity of neurons from the red nucleus, a mesencephalic structure involved in motor control, is under the influence of several neurotransmitters released from afferent fibers and/or from local interneurons. We have investigated the combined effects of gamma-aminobutyric acid (GABA) and noradrenaline (NA), both present at high levels in the red nucleus, on the firing activity of single rubral neurons recorded extracellularly in vivo on anesthetized adult rats. NA inhibited the firing activity of a large part of rubral neurons and induced excitatory or biphasic inhibitory/excitatory effects in a smaller group of cells. Neuronal firing was also inhibited by GABA in all the cells studied. When the effect of GABA was tested during continuous applications of NA, the magnitude of GABA response was modified in 58% of the cells: the effect of GABA was potentiated by NA in half of the responding neurons and was decreased in the remaining half. NA-induced potentiation of GABA response was mimicked by the alpha(2)-adrenoceptor agonist clonidine and was abolished by the alpha(2)-adrenoceptor antagonist yohimbine. On the other side, the decrease of GABA response was reproduced by the beta-adrenoceptor agonist isoprenaline and was blocked by timolol, an antagonist of beta-adrenoceptors. Neuronal firing activity was reduced by nipecotic acid, an inhibitor of GABA reuptake mechanism, and was instead increased during application of the GABA(A) receptor antagonist bicuculline, suggesting that rubral neurons in vivo were under tonic control by endogenous GABA. Both the inhibitory and the excitatory effects of NA were reduced in the presence of nipecotic acid and were instead potentiated during application of bicuculline, suggesting that NA responses were modified by endogenous GABA. Taken together, our results indicate a reciprocal modulation between the effects of GABA and NA on neuronal firing activity in the red nucleus of the rat: GABA depresses the responsiveness of rubral neurons to NA, whereas NA is able either to potentiate or to decrease the effects of GABA by activation of alpha(2)- and beta-adrenoceptors, respectively. The functional significance of such interaction, as well as the possible implication in diseases affecting motor control, will be discussed.

Action Potentials↗

Motor deficit induced by red nucleus lesion: re-appraisal using kainic acid destructions.

The motor deficits induced by red nucleus lesions have been well documented but so far based upon approaches destroying both cells and fibres of passage. In the present study we used kaïnic lesions, which are known to spare, at least partially, the fibres of passage in order to re-investigate the motor deficit induced by rubral lesion. Five cats were fully trained to perform a forepaw pointing movement towards a moving spot of light. Four of them underwent a bilateral neurotoxic lesion of the red nucleus; a fifth one, was used as a control, with the lesion being done electrolytically. Kaïnic lesions induced strong dysmetria with a tendency to over-reaching, and a delayed movement onset; after postoperative training, the dysmetria only persisted when reaching towards targets moving at high speed. The electrolytic lesion led to a much stronger deficit with an additional lengthening of the execution phase duration. Moreover, although overall accuracy could recover, time taken for movement initiation and execution stayed permanently impaired. In the light of these results a distinction can be made between the red nucleus syndrome per se and the one due to damage to fibres of passage.

Animals↗

Projection of the magnocellular red nucleus to the region of the accessory abducens nucleus in the rabbit.

The projection of the magnocellular red nucleus (RNm) to the region of the accessory abducens nucleus (AABD) was traced in rabbit using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). In one set of animals, recordings of antidromic responses from RNm neurons elicited by electrical stimulation of the rubrospinal tract were used to localize injections of WGA-HRP for orthograde labeling of RNm terminals. In a different set of animals, horseradish peroxidase was injected into the retractor bulbi muscle to retrogradely label motoneurons of the AABD. The positions of RNm fibers and terminals were examined and compared to the locations and distribution of AABD cell bodies and labeled dendrites. Analyses revealed that along the entire rostrocaudal extent of the AABD, RNm efferents terminate primarily lateral to, or in the lateral aspects of, labeled motoneurons. For the rostral AABD, RNm efferents terminate only lateral to the nucleus. Although the terminals are not positioned to contact cell bodies of the AABD, they could overlap with dendrites that extend in the lateral direction. RNm efferents terminate more extensively within the posterior AABD, overlapping within both dendritic and cell body regions of the nucleus. Even in this posterior region, however, RNm efferents were distributed primarily over the lateral half of the nucleus. These data show that RNm can monosynaptically influence the AABD, through primarily its lateral and posterior aspects. Our findings also show that a major target of RNm efferents is the reticular cell population located lateral to the AABD, suggesting that the RNm also may affect AABD motoneuronal output indirectly through its projection to reticular cells.

Abducens Nerve↗

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.

Animals↗

Motor co-ordinates in primate red nucleus: preferential relation to muscle activation versus kinematic variables.

1. Magnocellular red nucleus (RNm) neurones (n = 158) were recorded from two macaque monkeys during a tracking task using one of six single-degree-of-freedom manipulanda. This task allowed us to study discrete movements about most of the joints of the arm. Single-unit, kinematic and electromyographic (EMG) signals from ten to twenty muscles of the upper limb were collected for approximately 2 min while the monkey used a given manipulandum. Movements about different joints were studied by switching among manipulanda. 2. Cross-correlation functions were calculated between RNm discharge rate and the kinematic variables, position and velocity, and between RNm and each of the EMG signals. Statistically significant cross-correlation peaks were found in 24% of the position correlations, 22% of the velocity correlations and 32% of the EMG correlations. The highest correlations were for EMG, reaching above 0.60. The peak correlation provided an effective means of identifying neurones with strong functional relations to one or more movements and/or muscles. These could then be analysed in detail, on a trial-by-trial basis. 3. The similarity between the dynamics of EMG and velocity signals of many highly practised movements makes it difficult to determine which might be the more likely target of RNm control. Therefore, we sought exceptions to this pattern, in order to distinguish between these two possible modes of control. For example, at the end of a movement, muscles occasionally remained active as velocity approached zero. Small corrective movements were often accompanied by a disproportionately large EMG. During these periods, RNm activity usually followed the time course of one or more of the EMG signals as opposed to the velocity signal. In the majority of cases, RNm responses were bidirectional, less frequently unidirectional and rarely reciprocal. These patterns were similar to the patterns of muscle activity. They did not resemble the velocity signals unless the latter were passed through a rectifier. 4. The results support the hypothesis that the red nucleus generates motor commands in a muscle-based co-ordinate system. Covariation between RNm discharge and velocity may result indirectly from correlations between muscle activation and movement. We discuss how the cerebellar cortex might convert the distributed representation of target position, known to be present in the posterior parietal cortex, directly into dynamic, muscle-based commands in the rubro-cortico-cerebellar limb premotor network.

Animals↗

Cortical projections to the human red nucleus: a diffusion tensor tractography study with a 1.5-T MRI machine.

INTRODUCTION: Previous studies in apes and monkeys have shown that the red nucleus receives projections from the sensorimotor and premotor cortices, whereas other experiments carried out with injured human brains have found corticorubral projections issuing from associative areas. Therefore, we reassessed in vivo the human anatomical projections from the cerebral cortex to the red nucleus using diffusion tensor imaging (DTI) axonal tracking. METHODS: The connectivity between the cerebral cortex and the red nuclei of seven volunteers was studied at 1.5 T using streamlined DTI axonal tracking. RESULTS: Trajectories were constantly tracked between the red nuclei and the ipsilateral pericentral and prefrontal cortices, as well as the temporal cortex and the striatum in two subjects. Within the cerebral trunk, trajectories also include the superior cerebellar peduncle and the central tegmental tract. CONCLUSION: The human red nucleus receives its main afferences from the sensorimotor and prefrontal cortices.

Adult↗

Single-unit activity in red nucleus during the classically conditioned rabbit nictitating membrane response.

Previous investigations have suggested that the cerebellum and associated brainstem structures, including the red nucleus, are essential for the expression of the classically conditioned nictitating membrane (NM) response. The present study examined the firing patterns of extracellularly-recorded single units in the red nucleus of the awake rabbit during differential conditioning. Tones were used as conditioned stimulus (CS+ and CS-) and periocular electrostimulation was used as the unconditioned stimulus (US). Most units exhibited one or more changes in firing rate during the presentation of the CS, and increases in firing were much more common than decreases. The onset of some of these changes appeared to be time-locked to the onset of the CS ('CS-locked' responses), while other changes were time-locked to the onset of the CR ('CR-locked' responses). About one-third of all CS-locked changes were CR-dependent, meaning that the neuronal response was reduced when the CR did not occur. About two-thirds of all CR-locked responses preceded the onset of the CR, and lead times varied considerably across units. Many CR-locked units were located in what has been described as a dorsal face region of the red nucleus. Most units responded to the US, and some of the US responses were CR-dependent: i.e., a smaller US response was evoked when a CR preceded the US than when the CR was absent. Our results support the notion that cerebellum-brainstem circuits are involved in generating NM CRs.

Acoustic Stimulation↗

Cerebellar terminations in the red nucleus of Macaca fascicularis: an electron-microscopic study utilizing the anterograde transport of WGA:HRP.

The red nucleus (RN) of the macaque monkey is divided into a rostral two-thirds, the parvicellularis (RNp), which projects to the cerebellum by way of the inferior olivary nucleus, and a caudal third, the magnocellularis (RNm), which projects to the spinal cord via the rubrospinal tract. The RNp and RNm receive afferents from two principal sources: the cerebral motor cortices and the deep cerebellar nuclei. The terminations of these two afferent projections tend to be spatially segregated on rubral neurons, in that most corticorubral afferents terminate on more distal dendrites, and those from the deep cerebellar nuclei terminate more proximally. The present electron-microscopic analysis of the cerebellar terminations in the macaque RN provides anatomical evidence for the presence of labeled afferents in both divisions of this motor nucleus, following injection of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the deep cerebellar nuclei and the anterograde transport of the tracer to the RN. The cerebellar terminal afferents are large; contain numerous mitochondria and primarily rounded synaptic vesicles; and form asymmetric synaptic contacts with rubral neurons. Unlike other terminals in the nucleus, they possess an electron-lucent cytoplasmic matrix and less densely packed synaptic vesicles. They are termed "large, round, pale" (LRP) terminals because of the morphological characteristics that distinguish them from other afferent terminal types found in RN. Labeled cerebellar afferents in RNp and RNm contact primarily neuronal somata, proximal dendrites emerging from the cell body, large-diameter dendrites, and the spines of rubral neurons that arise from somata and proximal dendrites.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Cat red nucleus activity preceding movement depends on initiation conditions.

The activity of 98 Red Nucleus neurons was recorded in 3 cats operantly conditioned to perform a ballistic forelimb flexion movement triggered after a brief sound in a simple Reaction Time condition, or Delayed after the same sound in the presence of a tone cue. Fifty-eight task related neurons presented changes of activity in either one or both conditions. Forty-four of them were studied quantitatively and classified in 3 categories: 1) only 16% of the units presented similar changes of firing preceding the triggered or delayed movement; 2) most units (55%) presented different changes of activity in the two conditions: in the Delayed condition, the activation occurred earlier before the movement, and/or the change in magnitude was reduced or the pattern of activity was modified; 3) moreover, for 29% of the units, the change of activity observed before movement in the Reaction Time condition was severely reduced or even absent in the Delayed condition. For some of these neurons a building-up of activity was observed very early in the Reaction Time condition, during the preparatory period, well before the occurrence of the conditioned stimulus. These results show that the Red Nucleus activity preceding a movement is clearly dependent on its initiation conditions. The distinct patterns of unit firing observed in the Reaction Time condition and in the Delayed condition are tentatively related to the different preparation and initiation constraints determined by the behavioral conditions.

Action Potentials↗

[Neuronal mechanisms of red nucleus interaction with brain stem structures].

Axon collaterals of rubrospinal neurons to various brainstem structures were identified in acute experiments in cats using the technique of intracellular recording of antidromic action potentials in combination with collision testing. A systemic principle of organization of the rubrospinal influences as well as a tendency to synchronous arrival of rubral impulses at various brainstem centres are shown. Most of the brainstem centres are relay nuclei sending direct efferent projections to those cerebellar areas which, in turn, control the red nucleus activity. Besides this loop which provides dynamic cerebellar control of motor activity, the somatosensory information transmission from the dorsal column nuclei of the spinal cord directly to the red nucleus is shown. The recorded mono- and polysynaptic EPSPs evoked by stimulation of the dorsal column nuclei are characterized by peculiarities which suggest that they originate in various parts of the somadendritic membrane of the red nucleus neurons. The mechanisms of integration of the descending motor command by the red nucleus are discussed.

Animals↗

[Effect of electrical stimulation of red nucleus on acupuncture analgesia].

The function of red nucleus (RN) was important in motor control. This work was to study whether the RN influenced the effect of EA and the somatosensory afferent system. C-responses of spinal dorsal horn neurons (SDHN) were recorded as nociceptive responses. Electrical stimulation of RN could intensify the inhibitory effect of EA and inhibit nociptive response of SDHN. Naloxone (NX) could completely block that inhibition of RN. The result inferred that the RN can modulate both of somatomotion and somatosense. The endogenous opiate system is involved in the somatosensory modulation of RN.

Acupuncture Analgesia↗

Comparative study of the posterior red nucleus in baboons and gibbons.

The posterior red nucleus (PRN) was studied in two species of primates by the technique of retrograde degeneration of rubrospinal cells following transection of the spinal cord at different levels. The form of the PRN was reconstructed for both a quadruped monkey (baboon) and an anthropoid with erect posture (gibbon). The PRN contains polymorphic cells characterized by their very chromophilic and granular Nissl substance. These neurons vary in diameter from 25 micrometer to 70 micrometer. Some of them give rise to the rubrospinal tract. Baboon: The approximately 1,300 rubrospinal cells in this species are divided into two equal groups, one related to the contralateral forelimb, with axons ending between the second cervical and third thoracic segment, and the other related to the contralateral hindlimb, projecting caudally beyond T3. Following a high cervical lesion, nondegenerated cells of similar description remain throughout the nucleus. A significantly large group of these cells occurs medially and may be the source of fibers ending in the brain stem or cerebellum. Gibbon: In this species, the number of rubrospinal cells controlling the hindlimb is less than half that found in the baboon. This reduction in the gibbon is much greater for medium-sized cells, but is also significant for the giant cells. These results obtained from primates are compared with those reported for the cat. A possible function for the PRN in the control of limb movements is discussed from the viewpoint of phylogeny.

Animals↗

Eye movement-related neurons in the red nucleus.

Extracellular unit activity of the parvocellular red nucleus (RN) and spontaneous horizontal eye movements were recorded in adult, nitrous oxide-anesthetized and C1 transected cats. It was found that 7.5% of the neurons of each RN were related to spontaneous horizontal saccadic eye movements. Three types of neurons were observed: (1) bidirectional neurons which increased their frequency of discharge in relation to any horizontal eye movement; (2) unidirectional neurons which altered their frequency of discharge in relation to a horizontal eye movement of a precise direction; and (3) neurons which increased their frequency of discharge in relation to the rapid phase of an horizontal nystagmus. These 3 types of neurons modified their frequency of discharge before the initiation of the eye movement. One pair of oculomotor neurons recorded simultaneously in both RN showed a significant correlation coefficient. These results suggest that the RN may contribute to the preparation or execution of horizontal eye movements.

Animals↗