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PubMed1981

Classical conditioning mediated by the red nucleus in the cat.

We have attempted to develop a behavioral and neuronal model for classical conditioning in the corticorubrospinal system. A conditioned stimulus (CS) was applied to the cerebral peduncle (CP) in cats which had lesions that interrupted the corticofugal fibers caudal to the red nucleus. The unconditioned stimulus (US) was an electric shock to the skin of the forelimb that produced flexion of the limb. After pairing of the CS and US in close temporal association, an initially ineffective stimulus to the cerebral peduncle was found to give rise to the flexion of the elbow. Extinction of the conditioned response was achieved by applying the CS alone or by reversing the sequence of the stimuli (US-CS: backward pairing). Furthermore, the US alone did not produce an increase in the effectiveness of the CS stimulus. Finally, pairing the fixed CS stimuli with the US at random intervals did not produce any increase in performance in response to the CS. In these respects, the observed behavioral modification has the features of associative conditioning. Because the thresholds for and the strength of elbow flexion induced by stimulation of the nucleus interpositus of the cerebellum were identical in the experimental and control animals, the interpositorubrospinal system cannot be the site of the plastic change. Since the conditioned response is most probably mediated by the corticorubrospinal system, it is likely that a modification of the corticorubral synapses underlies this behavioral change.

Animals↗

PubMed2001

Role of primate magnocellular red nucleus neurons in controlling hand preshaping during reaching to grasp.

Reaching to grasp is of fundamental importance to primate motor behavior and requires coordinating hand preshaping with limb transport and grasping. We aimed to clarify the role of cerebellar output via the magnocellular red nucleus (RNm) to the control of reaching to grasp. Rubrospinal fibers originating from RNm constitute one pathway by which cerebellar output influences spinal circuitry directly. We recorded discharge from individual forelimb RNm neurons while monkeys performed a reach-to-grasp task and two tasks that were similar to the reach-to-grasp task in trajectory, amplitude, and direction but did not include a grasp. One of these, the device task, elicited reaches while holding a handle, and the other, the free-reach task, elicited reaches that did not require any specific hand use for task performance. The results demonstrate that coordinated whole-limb reaching movements are associated with large discharge modulations of RNm neurons predominantly when hand use is included. Therefore RNm neurons can at best only make a minor contribution to the control of reaching movements that lack hand use. We evaluated relations between the discharge of individual RNm neurons and electromyographic (EMG) activity of forelimb muscles during the reach-to-grasp task by comparing times of peak RNm discharge to times of peak EMG activity. The results are consistent with the view that RNm discharge may contribute to EMG activity of both distal and proximal muscles during reaching to grasp especially digit extensor and limb elevation muscles. Relations between the discharge of individual RNm neurons and movements of the metacarpi-phalangeal (MCP), wrist, elbow, and shoulder joints during individual trials of task performance were quantified by parametric correlation analyses on a subset of neurons studied during the reach-to-grasp and free-reach tasks. The results indicate that MCP extensions were consistently preceded by bursts of RNm discharge, and strong correlations were observed between parameters of discharge and the duration, velocity, and amplitude of corresponding MCP extensions. In contrast, relations between discharge and movements of proximal joints were poorly represented, and RNm discharge was not related to the speed of limb transport. Based on our data and those of others, we hypothesize that cerebellar output via RNm is specialized for controlling hand use and conclude that RNm may contribute to the control of hand preshaping during reaching to grasp by activating muscle synergies that produce the appropriate MCP extension at the appropriate phase of limb transport.

Animals↗

PubMed1999

Red nucleus neurons of Bcl-2 over-expressing mice are protected from cell death induced by axotomy.

The Bcl-2 proto-oncogene regulates apoptosis and prevents cell death. We studied the effect of Bcl-2 gene over-expression on the survival of axotomized red nucleus (RN) neurons after unilateral hemisection at cervical segment 4/5 (C4/5) in mice. Seventy-five percent of RN neurons survived in Bcl-2 over-expressing mice 1 or 2 months after surgery compared with only 55% of RN neurons in wild-type mice. However, Bcl-2 gene over-expression does not prevent lesion-induced shrinkage of RN neurons.

Animals↗

PubMed1984

An ipsilateral projection from the red nucleus to the lateral reticular nucleus in the cat.

Injections of the wheat germ agglutinin--horseradish peroxidase complex into the lateral reticular nucleus reveal that in addition to the well known contralateral rubroreticular connection, there is also a small but clear cut ipsilateral projection. Cells of various sizes participate in this ipsilateral pathway, and the retrogradely labelled neurons lie dispersed throughout the entire red nucleus.

Animals↗

PubMed1993

Differential effects of local inactivation within motor cortex and red nucleus on performance of an elbow task in the cat.

This study examined changes in the performance of a single-joint, elbow task produced by reversible inactivation of local regions within the proximal forelimb representation in area 4 gamma of motor cortex (MCx) and the red nucleus (RN) of the cat. Inactivation was carried out by microinjecting lidocaine, gamma-aminobutyric acid, or muscimol into sites where microstimulation evoked contraction of elbow muscles. Reaction time, amplitude, and speed (velocity or dF/dt) of position and force responses elicited during inactivation were compared to control values obtained immediately prior to inactivation. In addition, we assessed qualitatively the effects of inactivation on reaching, placing reactions, and proprioceptive responses to imposed limb displacement. In the single-joint task, injections in MCx did not increase reaction time (simple or choice) and produced modest and inconsistent reductions in response amplitude (mean -8%) and speed (mean -19%). In contrast, injections of the same amounts of inactivating agents in the forelimb representation of RN consistently increased reaction time (34.4%), and increased the reaction time coefficient of variability (32%). There were small reductions in response amplitude (-4%) and speed (-10%) which were less than those produced by MCx inactivation. During reaching, however, these same injections in MCx and RN produced a substantial loss of accuracy. For MCx, this was due, in part, to systematic hypometria: for RN, inaccuracy resulted from increased variability in paw paths. Placing reactions and corrective responses to imposed limb displacements were also depressed by the cortical and rubral injections. Our results suggest that the forelimb representation in RN plays a role in the initiation of the single-joint, elbow tracking response examined here. The RN may mediate cerebellar regulation of response timing, a function that is likely to be important for interjoint coordination. Although neurons in the forelimb representations of MCx may contribute to force generation in single-joint movements, their contribution to multijoint control appears to be more important and is examined in the subsequent report (Martin and Ghez 1993).

Animals↗

PubMed1994

Changes in retrogradely labelled neurones in the red nucleus and cortex after depletion of motoneurones by axotomy in neonatal rats.

Following nerve injury to the sciatic nerve in neonatal rats many motoneurones die, so that the target of the rubrospinal and corticospinal cord is altered. Retrograde labelling of neurones terminating in this region shows that, in the red nucleus as well as cerebral cortex, there is a significant reduction in labelled neurones on the side contralateral to the nerve injury. Thus neurones in the brain that give rise to descending fibres are influenced by the altered environment in the spinal cord following axotomy at birth.

Animals↗

PubMed1994

Pericruciate fibres to the red nucleus and to the medial bulbar reticular formation.

Extracellular single activity was recorded from pericruciate neurons in anaesthetized, paralysed, artificially ventilated cats. A total of 455 neurons were classified antidromically according to their sites of termination along the corticospinal tract and whether they sent collateral branches to the ipsilateral red nucleus and/or to the contralateral nucleus reticularis gigantocellularis. It was found that the majority of the branching fibres that reached the most caudal segments of the cord were fast conducting, while the slower branching axons tended to terminate at more rostral levels of the corticospinal tract. Most of the branching fibres terminated at bulbar and cervical levels (153/182: 84%), and the remaining ended at thoracic (21/182: 11.5%) and at lumbar (8/182: 4.4%) segments of the cord. The non-corticospinal, pyramidal tract fibres branched more (56%) than the corticospinal fibres (26.6%). Within the corticospinal neurons, the degree of branching decreased with distance along the spinal cord. While 57.5% of the pericruciate fibres that projected only as far as the pyramidal tract were slow conducting, the majority of the corticospinal neurons were fast conducting (74.6%). Both pyramidal tract and corticospinal neurons that sent branches to one or to the two sites tested were significantly faster conducting than the neurons which did not branch. A total of 101 corticorubral and corticobulbar neurons which did not respond to pyramidal tract stimulation was also recorded. The data can be of significance in the understanding of co-ordination of different muscles in order to couple movement and posture into a common act. The results are discussed from this point of view.

Animals↗

PubMed2001

Discharge of primate magnocellular red nucleus neurons during reaching to grasp in different spatial locations.

Reaching to grasp is of fundamental importance to primate motor behavior. One descending motor pathway that contributes to the control of this behavior is the rubrospinal tract. An important source of origin of the rubrospinal tract is the magnocellular red nucleus (RNm). Forelimb RNm neurons discharge vigorously during reach-to-grasp movements. RNm discharge is important for hand use, as coordinated whole-limb movements without hand use are not associated with strong discharge. Because RNm is functionally linked to muscles of the entire forelimb, RNm discharge may also contribute to use of the proximal limb that accompanies hand use. If RNm contributes to proximal limb use, we predict discharge to differ for reaches that differ in proximal limb involvement but require the same grasp. We tested this prediction by measuring discharge of individual RNm neurons while monkeys reached to grasp objects in four spatial locations in front of them. The animals reached from the waist to locations to the left, right, above, and below the shoulder of the "reaching" limb. RNm neurons of our sample were activated strongly during reach-to-grasp, and discharge of a third of the neurons tested depended on the spatial location of the object grasped. Discharge of RNm neurons and EMG activity of many of the distal and proximal forelimb muscles we tested were larger for reaching to grasp in the upper and/or right than lower and left target locations. Based on comparisons of each individual neuron's discharge patterns during reaches with and without preshaping the hand, we conclude that target location-dependent modulations in discharge rate of the majority of RNm neurons whose discharge differed for reaching to grasp in the four target locations contributed to aspects of hand preshaping that covaried with reach direction.

Action Potentials↗

PubMedDate not supplied

Participation of the red nucleus in motor initiation: unit recording and cooling in cats.

Cats were trained to release (Go) or not to release (No-go) a lever after a brief auditory signal, depending on the presence of an additional tone (No-go cue). Unit recording and cooling were made in the red nucleus (RN) contralateral to the performing limb. Three major results were found: (1) in the Go condition, we observed phasic increases of rubral firing, with a constant latency after the auditory signal and with an amplitude correlated to the latency of motor triggering (i.e. reaction time, RT); the tonic activity preceding the auditory signal could also be correlated to the RTs for some units; (2) in the No-go condition, there was no phasic increase of rubral firing after the auditory signal; the tonic activity during the presentation of the No-go cue was markedly decreased compared to the Go trials; (3) cooling of the RN increased the RTs and could also block the motor triggering. These results suggest that the RN is involved in setting and triggering a conditioned motor response according to sensory cues.

Animals↗

PubMed1998

MRI of the occipital cortex, red nucleus, and substantia nigra during visual aura of migraine.

The authors report a patient with migraine in whom they measured brain oxygenation indirectly during a visual aura by means of T2-weighted MRI. An aura of left homonomous quadrantanopia was accompanied by increased T2-weighted contrast intensity of bilateral regions in the occipital cortex, and the red nucleus and substantia nigra bilaterally. The mechanisms of these changes remain to be determined, but in this patient the migraine aura was associated with probable hyperoxia and not cerebral ischemia.

Adult↗

PubMed1997

Behavioural effects of selective serotonin reuptake inhibitors following direct micro injection into the left red nucleus of the rat.

The behavioural effects of selective serotonin reuptake inhibitors (paroxetine, sertraline, citalopram, fluvoxamine, fluoxetine) and reference compounds (N,N'-di(o-tolyl)guanidine, haloperidol, 3-(3-hydroxyphenyl)-N-(l-propyl)piperidine and chlorpromazine) were studied for their ability to produce dystonia and torticollis following direct micro injection into the left red nucleus of the rat, an area of the brain containing a high density of sigma2 receptors but relatively devoid of biogenic amine receptors. Each animal was monitored for abnormalities in posture and movement for a period of 30 min and then sacrificed 40 min following drug administation. Only fluvoxamine (100 nmol) and fluoxetine (100 nmol) elicited acute dystonic behaviour (1-5 min). The onset of dystonia was accompanied by facial spasticity, vacuous chewing movements and grooming behaviour which reflected the extent of dystonia. The dystonic behaviour following the direct intrarubal injection of fluvoxamine and fluoxetine suggest the possible activation of sigma2 receptors while citalopram, sertraline and paroxetine were without effect. The results of this study support the role of sigma2 receptors in the regulation and control of movement and coordination and provides preliminary evidence to suggest the in vivo activity of sigma receptors by fluoxetine and fluvoxamine.

1-Naphthylamine↗

PubMed1986

A new pathway from primary afferents to the red nucleus.

Evidence is provided that rubrospinal neurons receive feedback information from the periphery via pathways which bypass both the cerebellum and the cerebral cortex. It appears that the primary afferent fibers which ascend in the dorsal columns of the spinal cord give off collaterals via which they activate ascending tracts with axons in the ventral quandrants of the spinal cord. The existence of such pathways indicates that the red nucleus is part of a long feedback loop assisting the ongoing movement.

Animals↗

PubMed2000

The cytoarchitectonic and neuronal structure of the red nucleus in guinea pig: Nissl and Golgi studies.

The present studies were carried out on the brains of adult guinea pigs, Dunkin-Hartley strain. On the basis of preparations, they were stained according to the Nissl and the Klüver-Barrera method's; a short description of the cytoarchitectonics and the characteristics of the rubral cells were written. The red nucleus (RN) of the guinea pig is 1.2 mm in length. Three cellular parts in RN, and three classes (A, B, C) of the rubral cells were distinguished. Taking into consideration the predominant cell size, RN was divided into magnocellular part (RNm), parvocellular part (RNp) and intermediate part (RNi). On the basis of Golgi impregnated preparations four neuronal types (I, II, III, IV) were distinguished. To sum up, in the guinea pig were observed: the large, mainly multipolar (type I) and bipolar (type II) spiny being coarse (class A) in Nissl material; the medium-sized, triangular, aspiny (type III) corresponding to the fine cells (class B); and the small, both spiny and aspiny neurons (type IV), which are the fine or achromatic cells (classes B or C) in Nissl stained slices. The highest degree of dendritic branching was observed in type I, whereas the lowest in cells of types III and IV.

Animals↗

PubMed1986

Amino acid receptor mediated excitatory synaptic transmission in the cat red nucleus.

A study has been made of the effects of the selective N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovalerate (APV), and the broad spectrum excitatory amino acid antagonists, gamma-D-glutamylglycine (gamma-DGG), gamma-D-glutamylaminomethylsulphonate (GAMS), 4(p-chlorobenzoyl)-cis-piperazine-2, 3-dicarboxylate (pCB-PzDA) and kynurenate, have been examined on excitation evoked on neurones in the magnocellular red nucleus (m.r.n.) of the anaesthetized cat by stimulation of the interpositus nucleus (i.p.n.) and sensorimotor cortex, and by ionophoresed excitant amino acid agonists. The profile of activity of the excitatory amino acid antagonists on m.r.n. neurones was similar to that described on neurones in other areas of the central nervous system. APV selectively depressed responses to N-methyl-D-aspartate (NMDA), whereas the broader spectrum antagonists reduced responses to kainate and quisqualate as well as to NMDA. Neuronal responses to L-glutamate and L-aspartate were depressed by all the antagonists tested. I.p.n.-evoked monosynaptic responses of m.r.n. neurones were reversibly reduced by the broad spectrum antagonists, but were unaffected by APV. Cortically evoked mono- and polysynaptic excitatory responses were reversibly depressed by APV and the broad spectrum antagonist, pCB-PzDA. The action of APV corresponded with its ability to antagonize responses to NMDA. However, the cortically evoked responses appeared to be more sensitive to the actions of pCB-PzDA than to those of APV, although the former is a less effective antagonist of NMDA-induced excitation compared with APV. APV depressed excitation induced by cortical stimuli and L-glutamate and L-aspartate. However, there was no obvious correlation between the actions of the broad spectrum amino acid antagonists on synaptically evoked responses and those induced by L-glutamate or L-aspartate on the few neurones tested. These results are consistent with an amino acid being the transmitter in the interposito-rubral and cortico-rubral excitatory pathways which interacts with non-NMDA and both NMDA and non-NMDA receptors respectively. However, the identity of the transmitter acting at these receptors remains to be determined.

2-Amino-5-phosphonovalerate↗

PubMed1992

Elevated gene expression in the red nucleus after spinal cord compression injury.

Since the mechanism of injury in the majority of human traumatic spinal cord injuries involves rapid cord compression due to bone displacement or fracture-dislocation, we have used a compression injury model to examine the response of adult rat rubrospinal neurons to traumatic spinal cord injury. We have applied in situ hybridization techniques to examine levels of mRNA for cytoskeletal and growth-associated proteins. We report a population of magnocellular red nucleus neurons with elevated levels of T alpha 1 tubulin and GAP-43 up to four weeks post-lesion. In control animals, both probes had very low hybridization signals indistinguishable from background. These and other findings suggest that kinetic compression injuries of the adult spinal cord can result in regeneration-associated gene expression in intrinsic CNS neurons.

Animals↗

PubMed1997

The electrical activity is impaired in the red nucleus of dt(sz) mutant hamsters with paroxysmal dystonia: an EEG power spectrum analysis of depth electrode recordings.

The genetically dystonic (dt(sz)) hamster is an animal model of paroxysmal dystonia that displays attacks of sustained abnormal movements and postures in response to mild stress. Dysfunctions within the basal ganglia may be critically involved in the pathophysiology of dystonia in mutant hamsters. Furthermore, previous observations from autoradiographic studies pointed to an altered neural activity in the red nucleus (RN). In the present study, computerized EEG spectral analysis of depth electrode recordings from the RN was performed before and after dystonic attacks in freely moving dt(sz) hamsters and compared to age-matched non-dystonic controls. No epileptic activity was seen in any of the recordings, substantiating previous notions that paroxysmal dystonia in these mutants has no epileptogenic basis. The predominant EEG changes in RN of dystonic hamsters were a decrease in total power over the range of 1.25-42.00 Hz, a decrease in maximum power and a shift of frequency at maximum power to lower frequencies. With regard to selected frequency bands, there was a decrease in the alpha, beta and gamma band. Although the observed changes of neural activity in the RN are probably based on a primary dysfunction in related structures, the present data demonstrate its importance in the expression of dystonic movements.

Animals↗

PubMed1988

Bilateral pericruciate cortical innervation of the red nucleus in cats with adult or neonatal cerebral hemispherectomy.

We studied remodeling of the remaining corticorubral projections in adult cats sustaining a left cerebral hemispherectomy in adulthood or neonatally using cortical injections of [3H]leucine-proline. Injection sites and terminal fields were reconstructed from autoradiography-processed tissue. In all cats, the label filled similar extents of ares 4 gamma and 3a of the right frontal cortex. We used sections at 8 coronal planes throughout the red nucleus (RN) for computer-assisted analysis of visually estimated density and topography of distribution of terminal label, and for calculation of RN cross-sectional area. Additionally, at 3 coronal planes we further quantified terminal label using computerized procedures (number of particles for surface area). In all lesioned cats we found terminal label in the RN contralateral to the injection site with a topographic distribution similar to that of the RN ipsilateral to the injection in normal or lesioned cats and in absence of any significant shrinkage of the nucleus. The difference between the 2 age-at-lesion groups was that in the cats with neonatal ablation the density of contralateral terminal label was about double that seen in adult-lesioned subjects. However, the amount of contralateral labeling in adult-lesioned cats was substantial and represented a significant increase over the minimal labeling seen in normal cats. There were no differences between groups in labeling or size of the RN ipsilateral to the injection site. For reasons discussed, we interpret the label on the side of the hemispherectomy as representative of reinnervation of the cortically deafferented RN by crossing collaterals of fibers arising in the remaining motor cortex and not as lesion-sustained persistent prenatal connections.

Aging↗

PubMedDate not supplied

Long loop participation of red nucleus in contact placing in the adult cat with facilitation by tactile input at the spinal level.

This report focuses on the question 'Why does stimulation of a few hairs of a cat's unsupported paw lead to biceps activation and contact placing (CP) while stimulation of the supported paw does not?' The rubral system is used as the model; individual rubral neurons (RN) are recorded in the awake cat during CP and rubrospinal tract neurons (RTN) are identified by demonstrating antidromic invasion. Classes of RN were identified corresponding to each of the main stages of CP. In particular, a contingent, contact-locked category was identified, responding only if placing followed the contact. Another category, the pre-delayed movement-locked, responded 40-160 ms prior to delayed placing. Both of these categories imply that the rubral system dynamically participates (with other higher motor neurons) in CP, a conclusion strengthened by the positive relationship between RN discharge and movement parameters under varying load conditions. Physiological stimulation of the supported paw may fail to excite RN, which respond strongly to gentle contact of the unsupported paw (which leads to CP). Cooling or making permanent lesions in nucleus interpositus and dentatus drastically reduces resting and evoked RN and especially RTN activities in the awake cat. Some evidence of recovery was present by 4-6 weeks after the lesions. The effect of behavioral context was also studied on the biceps responses in the awake cat to a train of 3-4 pulses at 500 Hz delivered either to the red nucleus or to the rubrospinal tract (RT). The biceps responses were enhanced when the forepaw was removed from a support (the pre-condition for CP).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗