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[Representation of cutaneous sensitivity in the cat red nucleus].

Responses of the red nucleus neurons to the skin stimulation in unanestethized chronic cats showed most of the neurons to have wide receptive fields with areas stimulation of which caused an extremely intense and stable activation of respective neurons. The somatotopic principle of the cutaneous representation in the red nucleus was revealed. Destruction of the cerebellar nuclei and sensory motor cortex lowered the spontaneous activity of the red nucleus neurons, changed their responses to the skin stimulation, and caused the narrowing and the redistribution of the peripheral receptive fields preserving, however, the somatotopic character of the cutaneous representation in the red nucleus.

Animals↗

Responses of the red nucleus neurons to stimulation of the paw pads of forelimbs before and after cerebellar lesions.

Cerebellar cortex ablation releases deep cerebellar nuclei of monosynaptic inhibition from Purkinje cells. Therefore, it strengthens excitatory influence from Interpositus Nucleus (IN) upon Red Nucleus (RN), which results in much higher facilitation of the rubro-spinal neurons. This causes a big increase of spontaneous discharge rate, and eliminates brakes of discharges from responses generated by somatosensory stimuli. These two changes destroy content and timing of feedback information flowing through the spino-cerebello-rubro-spinal loop. This false bias of the feedback information, very important for fast postural adjustment and coordination of ongoing movements executed by central motor program, may at least in part be responsible for abnormal motor behavior evoked by cerebellar damage. Hemicerebellectomy resulted in dramatically reduced spontaneous activity and responses to limb stimulation because of severing a major input to the red nucleus from deep cerebellar nuclei. Due to direct somatosensory input to magnocellular Red Nucleus (mcRN) from the spinal cord that bypassed the cerebellum, the latency of response to limb stimulation was not changed and the narrower receptive fields were still present.

Animals↗

The red nucleus and mesencephalic tegmentum in a ranid amphibian: a cytoarchitectonic and HRP connectional study.

Movement control in vertebrates is a complex function that is known to involve several parallel systems. In amphibians, which lack the isocortical structures shown in mammals to initiate and control voluntary movements, supraspinal motor control systems have received surprisingly little attention. Because amphibians lack a corticospinal equivalent, coordination and control of all movement strategies must take place in non-cortical, supraspinal integrating centers. The rubro-cerebello-rubrospinal circuit is likely to represent a major motor control system in such vertebrates. In this anatomical investigation four mesencephalic tegmentospinal projection nuclei are described in ranid amphibians (Rana catesbiana and Rana pipiens): reticular formation, accessory optic complex, interstitial nucleus of Cajal, and the red nucleus. The red nucleus, which shows no distinct somatotopic organization, can be distinguished because it is the only one of the four that is predominantly contralateral in its projections. Horseradish peroxidase injections into the tegmentum and the cerebellum demonstrated that the red nucleus also maintains reciprocal connections with the cerebellum via the deep cerebellar nucleus. These connections could not be localized to any distinct region in the deep cerebellar nuclear mass, suggesting that this represents a single cerebellar recipient nucleus. Thus, anuran amphibians are shown to possess the major pathways that comprise the rubro-cerebello-rubrospinal circuitry in mammals.

Accessory Nerve↗

Functional connections between neurons of interpositus nucleus of the cerebellum and the red nucleus.

Patterns of functional connections between individual neurons of nucleus interpositus (IP) of the cerebellum and red nucleus (RN) were examined. This was assessed by cross-correlation of spike trains characterizing interaction between simultaneously recorded neurons. Direct interpositorubral connections were always excitatory in nature: direct inhibition was only found within and not between these nuclei. Shared inputs from common sources outnumber other types of interpositorubral connections. Patterns of connection between IP RN neurons could be influenced by sensorimotor cortex.

Afferent Pathways↗

Intrinsic and synaptic properties of turtle red nucleus neurons in vitro.

Burst discharges in the red nucleus are correlated with discrete limb movements. Intracellular recordings from red nucleus neurons in the in vitro turtle brainstem-cerebellum was performed to elucidate mechanisms underlying these bursts. Depolarizing intracellular current injection failed to demonstrate endogenous membrane currents that might produce burst discharges, and neurons did not exhibit significant spike frequency adaptation, which is a characteristic of synaptically driven bursts. Responses of red nucleus neurons to synaptic input demonstrated a late, slow depolarizing synaptic potential (slow EPSP) having a latency of 9-12 ms, and a maximal duration of 600 ms. it is concluded that neither intrinsic membrane responses, nor the duration of the slow EPSP, can fully account for the behavior of red nucleus neurons during burst discharge. We hypothesize that activity in the red nucleus is driven by a gradual recruitment of NMDA receptors, and lpr by polysynaptic excitatory pathways.

Animals↗

A behavioral study of the contributions of cells and fibers of passage in the red nucleus of the rat to postural righting, skilled movements, and learning.

Although the red nucleus consists of cells of origin for the rubro-spinal and rubro-olivary tracts, fibers of passage, including those of the superior cerebellar peduncle, which project from the cerebellum to the ventrolateral thalamus, pass through it. This study examined the relative effect of cell vs. fiber damage in the red nucleus on a number of behaviors thought to involve the red nucleus, including a skilled movement of reaching for food with a forelimb, postural righting on a surface and in the air, and learning a place response in a swimming pool test. Rats received unilateral or bilateral red nucleus lesions, using either the relatively cell-specific neurotoxins, ibotenic and quinolinic acid, or non-specific electrolytic anodal lesions. Both neurotoxic lesions effectively eliminated all red nucleus cell bodies, and in some animals they produced small cavities in the red nucleus and/or loss of cells in adjacent structures. Electrolytic lesions destroyed both cells and fibers, leaving a large cavity. The severity of the behavioral deficits were not related to the loss of red nucleus cells and there was a close relation between fiber damage and behavioral impairments on all of the tasks. The results suggest that for a number of behaviors, which have been thought to involve the red nucleus, impairments are more closely associated with fiber damage or damage to structures outside the red nucleus than they are to damage to cells of the red nucleus.

Animals↗

Loss of neurons in the red nucleus after spinal cord transection.

Red nucleus neurons, particularly those of the caudal one-half of the nucleus, die or severely atrophy following complete spinal cord transection at T9. The size of residual horseradish peroxidase-labeled cells was smaller at 10 and 15 weeks, but those survivors which could be labeled at 25 weeks were normal in size. Hematoxylin and eosin-stained sections of the red nucleus at 52 weeks postoperative showed loss of cells from all size groups.

Animals↗

Morphometric and experimental studies of the red nucleus in the albino rat.

Cytoarchitectural observations showed that the red nucleus of the albino rat consists of three distinct neuronal populations. Neurons with coarse Nissl bodies occupy the caudal end of the red nucleus and extend in diminishing number to the rostral tip. Neurons with finely granular Nissl material are the predominant cell type at the rostral tip of the red nucleus and interdigitate with the coarse neurons except at the caudal end of the nucleus. Coarse neurons, in contrast to fine neurons, are multiangular in contour and tend to be larger, although the two populations overlap in size. A population of interneurons, almost entirely smaller than the other cell types and less numerous, is ubiquitous within the red nucleus. Injections of horseradish peroxidase (HRP) at different levels of the spinal cord established that the coarse neurons on the contralateral side are the source of the rubrospinal tract and are topographically organized. The dorsal-medial part of the red nucleus emits axons which project to the cervical cord and the ventral-ventrolateral part of the nucleus to the lumbar cord. The thoracic cord receives projections from rubral neurons at intermediate positions. Further, coarse neurons from the entire rostrocaudal axis of the red nucleus contribute fibers to the rubrospinal tract.

Animals↗

Evolution of the red nucleus and rubrospinal tract.

A red nucleus, defined by its relative position in the tegmentum mesencephali, its contralateral rubrospinal or rubrobulbar projections and by crossed cerebellar afferents, is found in terrestrial vertebrates and certain rays. A crossed rubrospinal tract occurs in anurans, limbed urodeles and reptiles, birds and mammals, but is apparently absent in boid snakes, caecilians and sharks. A distinct rubrospinal tract is found in certain rays which use their enlarged pectoral fins for locomotion. A crossed tegmentospinal tract, possibly a rubrospinal tract, is found in lungfishes. Although evidence was presented for a rubrospinal tract in more advanced snakes, the available experimental data in lower vertebrates suggest that the presence of a rubrospinal tract is related to the presence of limbs or limb-like structures. In the connectivity of the red nucleus in terrestrial vertebrates, 'levels' of complexity can be distinguished, paralleled by the development of the cerebellum. These 'grades of organization' are probably related to the type of motor performance the particular terrestrial vertebrates are capable of.

Afferent Pathways↗

Is there a reciprocal connection between the red nucleus and the interposed cerebellar nuclei? Conclusions based on observations of anterograde and retrograde transport of peroxidase-labelled lectin in the same animal.

The rubrointerposital projection was studied in cats where wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was implanted in various parts of the interposed nuclei. No retrogradely labelled rubral cells were observed following implantations in the posterior interposed nucleus, and only very few such cells were identified in the contralateral red nucleus after implantations restricted to the anterior interposed nucleus with no contamination of cerebellar white matter or cortex. However, when WGA-HRP was delivered by a pressure injection, which in addition to the anterior interposed nucleus included the adjacent white cerebellar matter along the needle track and the overlying cortex, many retrogradely labelled cells were present contralaterally in the magnocellular red nucleus, with some also found in its rostral parvicellular part. The same observation was made when injection of free HRP exceeded the boundaries of the anterior interposed nucleus. These observations indicate that there is a negligible projection from the red nucleus to the contralateral interposed cerebellar nuclei. What has been considered to be rubrointerposital cerebellar fibres probably is the projection to the cerebellar cortex (Exp. Brain Res., 50 (1983) 353-358). Anterogradely labelled fibres could be followed from the implantations in the posterior interposed nucleus to a medial crescent of the entire contralateral red nucleus. Caudal as well as rostral parts of the posterior interposed nucleus project into the same area of the red nucleus. Implantations restricted to the anterior interposed nucleus label a projection to the contralateral magnocellular red nucleus which is topographically organized. The caudal part of the anterior interposed nucleus projects to the dorsomedial portion of the magnocellular red nucleus, the rostral part to its ventrolateral portion. In addition, a mediolateral organization in the anterior interposed nucleus coincides with a caudorostral arrangement in the red nucleus. This topical arrangement corresponds to what has previously been observed in cat and monkey, but due to the small implantation sites used in the present study a more precise mapping of the projection has been obtained. Furthermore, our implantations of WGA-HRP into the red nucleus show especially well the latter topical arrangement in the projection. The observations mentioned above are discussed and related to previous studies of the rubrocerebellar and cerebellorubral projections.

Animals↗

The morphology and cytoarchitecture of the red nucleus of the one-humped camel (Camelus dromedarius).

The red nucleus of the camel was delineated and reconstructed. For this purpose, three camel brain stems were used for making serial sections in the transverse, sagittal and horizontal planes after double embedding in celloidin-paraffin. All sections were mounted. Nissl and nissl-myelin methods were used for staining. The red nucleus was reconstructed by using a Leitz drawing device; it was seen to have the shape and form of an egg with a flattened medial surface. The red nucleus measures 8.35 mm (length) X 5.00 mm (width) X 3.70 mm (height) and extends from just caudal to the oculomotor nerve fibres to the fasciculus retroflexus rostrally. Five cell types were seen namely, giant, large, medium, small and minimus. The red nucleus shows a larger rostral parvocellular and a smaller caudal magnocellular divisions. The parvocellular division shows three subdivisions namely, the pars veniralis, pars dorsomedialis and cornu lateralis. The red nucleus and its giant cells are the largest reported in literature so far; the giant cells are quite similar to the large ventral spinal motor neurons. The camel cerebellum is very big and this fact along with the greatly developed red nucleus and rubrospinal tract may account for the great muscular control and coordination necessary for the camel to survive in the peculiar desert environment, it is exposed to.

Animals↗

Red nucleus lesions impair overground locomotion in rats: a kinetic analysis.

The red nucleus is a prominent brainstem nucleus in mammals which is thought to be involved in production of skilled limb movements. The presence of the red nucleus and associated rubrospinal tract in animals that do not produce skilled limb movements, however, suggests that these structures might also be involved in control of more general limb actions, such as those occurring during locomotion. The present study investigates this question by measuring the three-dimensional ground reaction forces produced by locomoting rats with unilateral excitotoxic lesions of the red nucleus. Twenty-four to 48 h after the lesion, rats moved with an asymmetric gait during which abnormal braking and propulsive forces were produced during the dual contact time of the forelimb contralateral to the lesion and the ipsilateral hindlimb. Rats did not recover normal symmetrical locomotion within the 55-day duration of the study. The persistent asymmetry produced by red nucleus ablation provides the first unequivocal demonstration that the red nucleus plays a role in ongoing overground locomotion in the rat. Species differences in phylogeny and connectivity of the red nucleus are discussed, as well as the possibility that there is a general compensatory response to unilateral CNS injury in the rat.

Animals↗

Changes in motor performance and rubral single unit activity in cats after microinjections of serotonin into the red nucleus area.

The serotonergic control exerted on the red nucleus (RN) was studied in unrestrained cats during the performance of a simple reaction time task which consisted of releasing a lever in response to an auditory go-signal. The effects of microinjections of serotonin-oxalate salt into the rubral area on the motor activity and on the firing of neurons recorded concomitantly in the red nucleus were investigated. Injections of serotonin (5-HT) (200-400 ng) into the red nucleus or its dorsal border induced subtle alterations in the conditioned motor performances but had no major effects on the spontaneous motor behavior. The changes in the conditioned motor output (an increase in the static force exerted on the lever and a speeding up of the lever release) are reminiscent of the facilitatory influence of serotonin on various motor reflexes previously reported. Changes in the neuronal activity were observed concomitantly with the effects on the motor output: 5-HT either enhanced or reduced the firing rate of the rubral neurons. These effects were apparently dependent on the discharge pattern of the neurons during the static motor activity. The results suggest that the serotonergic input to the red nucleus may participate in motor control by exerting a dual modulatory action on the activity of rubral neurons.

Animals↗

Somatosensory and movement-related properties of red nucleus: a single unit study in the turtle.

Extracellular recordings were performed from turtle red nucleus neurons to examine their responsiveness to peripheral somatic stimulation and to study differences between rubral sensory and movement-related responses. In pentobarbital sodium-anesthetized or decerebrate turtles, red nucleus neurons could be divided into two categories based on their response characteristics. The first group, which included 87% of neurons studied, had low spontaneous rates of activity and responded with excitation to electrical stimulation of the spinal cord or the cerebellum, or during active movement of the contralateral limbs. Neurons in this category were likely to be rubrospinal cells. The remaining 13% of cells studied had higher rates of spontaneous discharge and were inhibited by electrical stimulation or during active movement. These cells might be rubral GABAergic interneurons. Single red nucleus neurons responded with excitation and/or inhibition to somatosensory stimulation. Unlike the motor fields, which were restricted to a single contralateral limb, red nucleus sensory receptive fields were wide and often bilaterally distributed. Rubral responsiveness to sensory stimulation was found to be significantly diminished during active limb movements, thereby suggesting that sensory inputs to the red nucleus are not used for the on-line modification of motor commands. Inactivation of the cerebellar cortex enhanced the sensory responsiveness of rubral neurons and expanded the size of red nucleus receptive fields. These results suggest that the red nucleus receives substantial sensory input, and that the cerebellar cortex can modify the flow of sensory information to the red nucleus.

Animals↗

[Intracellular study of the formation of new synapses and collateral sprouting of red nucleus neurons after destruction of the cerebellar nucleus interpositus in the adult cat].

Responses of red nucleus neurons to stimulation of ipsilateral cerebellar nucleus interpositus were studied in cats after lesion of contralateral cerebellar nucleus interpositus within the period ranging from two weeks to one year and seven weeks. Recording of fast and slow mono- and polysynaptic EPSPs showed collateral sprouting of axons of interposito-rubral neurons to occur in various parts of soma-dendritic membrane of rubro-spinal neurons. Stimulation of ipsilateral cerebellar nucleus interpositus evoked antidromic activation in many red nucleus neurons, suggesting the sprouting of axon collaterals from rubro-spinal neurons onto the neurons of ipsilateral cerebellar n. interpositus projecting to the red nucleus.

Animals↗

Red nucleus stimulation inhibits within the inferior olive.

Red nucleus stimulation inhibits within the inferior olive. J. Neurophysiol. 80: 3127-3136, 1998. In the anesthetized cat, electrical stimulation of the magnocellular red nucleus (RNm) inhibits responses of rostral dorsal accessory olive (rDAO) neurons to cutaneous stimulation. We tested the hypothesis that RNm-mediated inhibition occurs within the inferior olive by using stimulation of the ventral funiculus (VF) of the spinal cord in place of cutaneous stimulation of the hindlimb. Fibers in the VF terminate on hindlimb rDAO neurons, so inhibition of this input would have to occur within the olive. rDAO responses elicited by VF stimulation were inhibited by prior stimulation of the RNm, indicating that inhibition occurs within the olive. In contrast, evoked potentials recorded from the VF or dorsal columns following hindlimb stimulation were not affected by prior stimulation of RNm, indicating that stimulation of the RNm does not inhibit olivary afferents at spinal levels. RNm stimulation that inhibited rDAO responses had little effect on evoked somatosensory responses in thalamus, indicating that inhibition generated by activity in RNm may be specific to rDAO. To test limb specificity of RNm-mediated inhibition, conditioning stimulation was applied to the dorsolateral funiculus at thoracic levels, which selectively activates RNm neurons projecting to the lumbar cord. Stimulation at thoracic levels inhibited evoked responses from hindlimb but not forelimb regions of rDAO, suggesting that inhibitory effects of RNm activity are limb specific. Several studies have reported that olivary neurons have reduced sensitivity to peripheral stimulation during movement; it is likely that RNm-mediated inhibition occurring within the olive contributes to this reduction of sensitivity. Inhibition of rDAO responses by descending motor pathways appears to be a salient feature of olivary function.

Animals↗

Effects of red nucleus inactivation on burst discharge in turtle cerebellum in vitro: evidence for positive feedback.

1. In behaving animals the red nucleus produces sustained action potential discharge during movements of the limbs. These bursts are thought to encode parameters of movement and thereby represent motor commands. Similar bursts can be recorded in the in vitro brain stem-cerebellum from the turtle. In this preparation, sustained discharge of red nucleus neurons was postulated to be generated by N-methyl-D-aspartate-mediated cellular mechanisms acting in combination with positive feedback in a recurrent cerebellorubral network. The present study was designed to test this positive feedback hypothesis. During recording of sustained discharge in the deep cerebellar nuclei and cortex, the red nucleus was reversibly inactivated by microinjection. The positive feedback hypothesis would be supported if activity in the cerebellum was attenuated by inactivation of the red nucleus. A nonrecurrent source of excitation would have to be postulated if cerebellar activity was unaffected. 2. Extracellular single-unit recordings were made from neurons in the deep cerebellar nuclei, cerebellar cortex, and vestibular nuclei. Burst discharges were evoked by brief electrical stimuli applied to the spinal cord that activated sensory structures. During inactivation of the red nucleus, sensory projections to the cerebellum that may evoke burst discharge were unaffected. Pressure microinjections of cobalt, lidocaine, gamma-aminobutyric acid (GABA), or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to reversibly inactivate the red nucleus. Saline injections were also tested. 3. Sustained discharge of all neurons recorded in the lateral cerebellar nucleus was greatly attenuated or blocked completely by injection of the pharmacological agents into the red nucleus. These effects were reversible. Of the recordings in the cerebellar cortex, 63% of these were blocked. All four compounds tested were effective blockers of the bursts, although the effects of GABA were less potent than the others. Saline injections into the red nucleus showed no effect. Burst discharges of single units recorded in either the medial cerebellar nucleus or the vestibular complex, which do not receive input from the red nucleus, showed no effect of red nucleus inactivation. 4. The results showed that sustained discharge in the cerebellum was significantly attenuated by inactivation of the red nucleus even though sensory input that may trigger the bursts was intact. These data support the hypothesis that sustained discharge in the cerebellorubral circuit is generated by a distributed neuronal network that uses positive feedback. The results have implications for mechanisms underlying normal brain function and some motor disorders.

Action Potentials↗

The effects of reversible inactivation of the red nucleus on learning-related and auditory-evoked unit activity in the pontine nuclei of classically conditioned rabbits.

The pontine nuclei carry auditory conditioned stimulus information to the cerebellum during classical conditioning of the nictitating membrane response in rabbits. In well-trained animals learning-related as well as stimulus-evoked unit activity can be recorded throughout the pontine nuclei but particularly in the lateral and dorsolateral pons. Recent work in our laboratory has provided evidence that the learning-related unit activity in the pons is dependent on the interpositus nucleus and that the pons is not a site of essential plasticity for the learned response. In the present study we considered the question of whether learning-related unit activity might be projected from the interpositus nucleus to the pons through the red nucleus, a primary output target of the interpositus and a structure known to be essential for expression of the learned response. Multiple unit recordings were taken from lateral and dorsolateral pontine locations in well-trained rabbits before and during cooling of the red nucleus. Analysis of pooled data for all recording locations within the lateral and dorsolateral pons indicated that reversible inactivation of red nucleus abolished both stimulus-evoked and learning-related unit activity. However, we also found discrete recording locations where stimulus-evoked and learning-related unit activity were attenuated but not abolished by red nucleus cooling.

Animals↗