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PubMed1983

Effects of age and strain differences on the red nucleus of the mouse mutant Dystonia musculorum.

The mouse mutant Dystonia musculorum exhibits pathological changes in the magnocellular neurons of the red nucleus. The present study shows that allelic differences occur in the age of onset and severity of this pathology. The magnocellular neurons of the Jackson allele (dtJ) almost completely disappear prior to 4 weeks of age while some of these cells are retained in the adult of the Albany strain (dtAlb). However, acetylcholinesterase histochemistry suggests that the remaining rubral neurons in dtAlb are nonfunctional. This pathology may contribute to the severe locomotor disturbances seen in these animals.

Acetylcholinesterase↗
PubMed1977

Pharmacology of the brachium conjunctivum: red nucleus synaptic system in the baboon.

Acetylcholine, biogenic amines, and certain amino acids were applied by microiontophoresis to parvicellular and magnocellular red nucleus (RN) neurons of baboon while recording brachium conjunctivum (BC)-evoked and amino acid-evoked unit discharge from these neurons. Glycine, gamma-aminobutyric acid, and beta-alanine were potent depressants of BC-RN synaptic transmission, amino acid-evoked firing, and spontaneous activity of all RN neurons studied. Glycine was clearly more potent than the other 2 depressant amino acids. L-Glutamic and DL-homocysteic acid were strong excitants of all RN neurons tested. Dopamine, noradrenaline, and 5-hydroxytryptamine depressed the excitability of both parvicellular and magnocellular RN neurons; no excitatory effects were observed with these biogenic amines on RN neurons. Acetylcholine increased the rate of firing of spontaneously discharging parvicellular RN neurons and facilitated the amino acid-induced firing of these same neurons. Acetylcholine did not facilitate BC-RN synaptic transmission nor could this transmission be blocked by cholinergic antagonists. Unlike parvicellular RN neurons, the responsiveness of magnocellular neurons was either unaltered by acetylcholine or slightly decreased. These experiments demonstrate a difference in the pharmacologic responsiveness of parvicellular and magnocellular RN neurons to acetylcholine but do not provide evidence for a cholinergic input to RN via the brachium conjunctivum.

Acetylcholine↗
PubMed1976

Comparison between red nucleus and precentral neurons during learned movements in the monkey.

Monkeys were trained to depress a hold key for a period of 2 sec. After this hold period, either a red or a green cue lamp appeared in random sequence. The red lamp required the monkey to move his hand from the hold key to a target button within 1 sec of the cue presentation. The green lamp required continued depression of the hold key for 1 sec following presentation of the cue. Correct performance was reinforced with fruit juice. In comparing poststimulus and peri-response latencies of 48 red nucleus (RN) and 46 percentral gyrus (PG) units related to the arm movement triggered by the red lamp, the onset of activity in most RN units occurred after the onset of activity in most PG neurons. For 48 RN neurons, the peak of the distribution of onset times was shifted 120 msec later than for 46 neurons. This delay between PG and RN is even greater than the delay between PG and postcentral gyrus. It is known that RN receives powerful inputs both from the sensorimotor cortex and from cerebellum--and it seems possible that the activity in RN was dependent on the combined action of these two inputs, with sensory feedback from movement (relayed via postcentral gyrus and/or cerebellum) being one input, and a central program from cerebellum and/or precentral gyrus being the other input.

Action Potentials↗
PubMedDate not supplied

Effects of cortical stimulation on red nucleus neurons in the guinea pig.

The aim of the present work was to study the control that the cerebral cortex exerts on red nucleus (RN) neurons in the guinea pig. The experiments were carried out in anaesthetized animals. Electrical stimulation of localized cortical foci was performed by tungsten microelectrodes in frontal and parietal regions containing sensorimotor representations of the body. Single unit RN activity was extracellularly recorded through glass micropipettes, and the encountered RN neurons were recognized by searching their peripheral receptive field. Then, corticorubral influences were tested on RN neurons whose receptive field was located in the same body regions where motor responses were evoked by cortical stimulation. The stimulation with a single pulse evoked complex responses, typically consisting of long lasting inhibitions sometimes preceded by a weak facilitation and always followed by an excitatory rebound. The application of a second pulse modified this pattern, depending on the time interval between the two stimuli. In fact, the reduction of the interval below 300 ms enhanced the excitatory components whereas it shortened the inhibitory component; moreover, an "early" facilitation was evoked but only at intervals as short as 50-150 ms, or less. These results suggest that the corticorubral control may vary according to different levels of cortical activation, becoming more and more facilitatory as the cortical discharges increase from low frequency values (tonic activity) towards high frequency values (phasic activity).

Animals↗
PubMed1996

Does the red nucleus provide the tonic support against which fractionated movements occur? A study on forepaw movements used in skilled reaching by the rat.

The red nucleus (RN) is a prominent structure in the motor system of mammals and is thought to play a role in the control of limb movement. In the rat, there are contradictory reports concerning its role in controlling movements of the paw and digits in grasping food in skilled reaching tasks. Some studies report severe impairments in the effectiveness of limb movement and impairments in grasping movements, whereas other studies report only mild impairments. This study is designed to resolve this issue by examining limb and paw movements in rats with RN lesions using a new high-speed video filming procedure. It was found that unilateral ibotenic acid lesions of the RN do not impair reaching or grasping success with the contralateral to the lesion. Reaching movements are changed, however. Control rats aim their paw by adducting the elbow, pronate their paw by abducting the elbow, and they place their digits over the food with a lateral to medial arpeggio pattern. In rats with RN lesions, aiming and pronating are reduced and the arpeggio movement does not occur. Rather, the food is grasped with a flexion of the digits as the limb is retracted. This change results in a very rapid grasp and an absence of a pause in limb transport during grasping. These impairments and the 'release' of the grasp response suggests that the RN may provide the tonus or supporting framework that momentarily immobilizes the limb so that arpeggio and grasping movements can occur. It is suggested that the function of the RN more generally may be to provide a tonic framework against which the motor cortex can produce more fractionated movements.

Animals↗
PubMedDate not supplied

Cerebellar projections to the red nucleus of the cat.

The organization of cerebello-rubral projections in the cat was studied after injection of Diamidino yellow and/or horseradish peroxidase into the red nucleus (RN). The nucleus interpositus posterior projects to the rostral RN and the nucleus interpositus anterior to the caudal RN. In each case only sparse retrograde labeling was observed in the nucleus lateralis. These projection zones do not correspond with the organization of rubrospinal projections.

Animals↗
PubMed1991

Distribution of motor cortical neuron synaptic terminals on monkey parvocellular red nucleus neurons.

We determined the location of 54 horseradish peroxidase (HRP)-labeled motor cortical neuron synaptic terminals on 17 parvocellular neurons in the monkey red nucleus. Synaptic terminals and their postsynaptic elements were identified and reconstructed, using light- and electron-microscopic techniques, from serial thick and thin sections. Terminals were found on proximal and distal dendrites of small and medium-sized parvocellular neurons, where they formed excitatory synapses. Some were 180 microns from cell somata. Approximately half of the labeled terminals, aside from those located at dendritic origins, were situated strategically at or near dendritic branch points. Since monkey parvocellular neurons show little activity during movement, the obvious next question is this: How and in what way does motor cortex influence these cells?

Animals↗
PubMed1993

Correlation of primate red nucleus discharge with muscle activity during free-form arm movements.

1. We recorded from 239 neurons located in the magnocellular division of the red nucleus of four alert macaque monkeys. At the same time, we recorded electromyographic (EMG) signals from as many as twenty electrodes chronically implanted on muscles of the shoulder, arm, forearm and hand. We recorded EMG signals for periods ranging from several months to a year. 2. The monkeys were trained to perform three free-form food retrieval tasks, each of which activated all of the recorded muscles and most of the neurons. The 'prehension' task required simply that the monkey grasp a piece of food from a fixed point in space. The 'barrier' task required the monkey to reach around a small barrier to obtain the food, and the 'Kluver' task required that food be removed from small holes. During the prehension task, we found approximately equal numbers of neurons that were strongly active while the hand was being moved toward the target (70% of units), and while the food was being grasped (60%). Relatively few units were active as the hand was returned to the mouth (15%). 3. Data files of 1-2 min duration were collected while the monkey performed a single behavioural task. Whenever possible, we recorded files for all three tasks from each neuron. For each file we calculated long time-span analog cross-correlations (+/- 1.28 s) between instantaneous neuronal firing rate and each of the full-wave rectified, low-pass filtered EMG signals. We used the peak correlation and the time of the peak as two summary measures of the functional relation between modulation of neuronal activity and EMG. 4. The magnitude of the strongest correlations was between 0.4 and 0.5 (normalized to a perfect correlation of +/- 1.0). Distal muscles were the most frequently correlated, and extensors were more frequently correlated than flexors. For all monkeys, the lags for well correlated muscles were distributed broadly about a uni-modal value near 0 ms. Eighty five per cent of the correlations larger than or equal to 0.25 had peaks between -150 and 200 ms. 5. The activity of each neuron was represented in a muscle co-ordinate system by an n-dimensional 'functional linkage vector', each element of which was the peak correlation with one of n muscles. The vector for any given neuron points in a particular direction in muscle space, depending on the similarity between the activity of the neuron and the activity of each muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Red nucleus: role in motor control.

Experimental reports in the past year have provided a better understanding of the motor functions of excitatory and inhibitory neurotransmitters in the red nucleus, and of the sensorimotor properties of single rubral neurons. These data fit well within the framework of a neural network model of the rubrocerebellar system.

Animals↗
PubMed1985

Magnocellular red nucleus activity during different types of limb movement in the macaque monkey.

Three hundred and thirty-four neurones located in the magnocellular division of red nucleus (r.n.m.) were studied in three alert macaque monkeys. These cells had low discharge rates at rest and produced high frequency bursts during movement. Single cells were selectively active for movement of one body part, and a motor somatotopy was evident. From dorsal to ventral we encountered cells related to movements of the face, contralateral upper limb, contralateral lower limb and, in one case, the tail. Free-form tests indicated that 76% of upper-limb cells were preferentially related to hand and finger movements, and 84% of lower limb cells were preferentially related to foot and toe movements. Quantitative tests of movement relations were based on depths of modulation in discharge rate recorded while the monkeys operated several devices that served as manipulanda in a tracking task; each device elicited a different movement. We conducted 220 tests on eighty-one cells using eleven devices. The modulation in discharge rate exceeded a 50 pulses/s criterion level in seventy-nine cases; eleven were well related to proximal movements, twenty-two to movements of the digits and forty-six to a co-ordinated hand movement elicited by a device called the twister. Both unidirectional and bidirectional patterns of bursting were frequent. A few cells showed reciprocal patterns consisting of a large increase in rate for one direction of movement and a small decrease for the other. The bursts in discharge preceded movement onset (97% of 132 cases) by an average of 135 ms. Electromyographic activity in forearm muscles preceded movement by about 55 ms. In some cases we recorded from a single cell while the monkey operated two, three or four devices. Depth of modulation on the twister device was twice that on a proximal device in nine cases whereas one case showed a proximal device preference; five cases showed overlap. Comparison between twister and digits yielded ten cases of twister preference, four of digit preference and twenty cases of overlap. A directional preference was found for ten out of eleven cells responsive during active movement restricted to the metacarpo-phalangeal joints, and in all cases the preferred direction was extension. Responses to natural somatosensory stimulation were weak or absent for the majority of cells. When present, sensory fields were confined to the same limb but were frequently out of register with motor fields.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed2003

Responses of the red nucleus neurons to limb stimulation after cerebellar lesions.

Two series of experiments concerning the effects induced by unilateral cerebellar lesions on background activity and responses of red nucleus neurons contralateral to lesion sites are reported in this short review. The first series describes the effects of cerebellar cortex ablations, the second reports the results of hemicerebellectomy. The major source of input to the deep cerebellar nuclei, the Purkinje cells of the cerebellar cortex are known to be inhibitory. Removal of this influence by cerebellar cortex lesion results in an increase of the interpositus neurons background activity. This effect strengthens the interpositus excitatory influence upon rubral neurons by evoking exaggerated depolarization and enhancing sensitivity of these cells to somatosensory volleys. This causes a considerable increase in the background firing, eliminates the pauses in discharges occurring in responses generated by somatosensory stimuli, and augments the excitatory rebound. These changes destroy the content and timing of feedback information flowing through the spino-cerebello-rubro-spinal loop, and are, at least in part, responsible for motor deficits of cerebellar dysfunction. Hemicerebellectomy reduces drastically spontaneous firing of rubro-spinal neurons and simplifies response patterns. Due to direct spino-rubral pathways the latency of response is not changed.

Animals↗
PubMed1986

Sprouting of GABAergic synapses in the red nucleus after lesions of the nucleus interpositus in the cat.

An immunocytochemical study using anti-GAD serum was performed to examine the plastic changes of GABAergic inhibitory synapses in the red nucleus (RN) after lesions of the nucleus interpositus (IP) of the cat. Light-microscopic analyses revealed that 20-175 d after the unilateral lesion of the IP, somatic profiles of large neurons in the magnocellular RN contralateral to the lesion were more densely covered with GAD-immunoreactive puncta than those in the ipsilateral RN. Electron-microscopic analyses demonstrated that the GAD-immunoreactive puncta observed with the light microscope were synaptic terminals and that the number of GAD-immunoreactive synaptic terminals per unit length of somatic membrane of RN neurons was increased on the deafferented side. The GAD-immunoreactive terminals on somata of RN neurons made symmetric synaptic contacts with somatic membranes on both the deafferented and control sides. The number of immunoreactive synapses on somata of RN neurons was markedly increased on the deafferented side following IP lesion, whereas that of the unlabeled asymmetric synapses was decreased. These observations indicate that new GABAergic synapses were formed on somata of RN neurons after deafferentation from the IP.

Afferent Pathways↗
PubMed1983

In vitro radioautographic study of the monoaminergic innervation of cat red nucleus. Identification of serotoninergic terminals.

This study emphasizes the existence of a dense plexus of serotoninergic nerve terminals having specifically accumulated tritiated serotonin in vitro in the red nucleus of cat. These terminals innervate the whole rostrocaudal extension of the nucleus, being frequently in close apposition to the cell bodies and proximal dendrites of magnocellular neurons in its caudal part. A possible involvement of this serotoninergic input in the modulation of cerebello-rubro-spinal activity is proposed.

Animals↗
PubMedDate not supplied

Red nucleus and motor cortex: parallel motor systems for the initiation and control of skilled movement.

This study examines the differential contributions of motor cortex (MCx) and red nucleus (RN) neurons to the initiation of a targeted limb response and to the control of trajectory. These questions were assessed in two ways. First, by comparing the characteristics of task-related neuronal activity in MCx and RN. Second, by determining the changes in reaction time and trajectories produced by the reversible inactivation of corticospinal fibers in the crus cerebri (CSTc), the rubrospinal tract (RST) and the RN, using microinjections of lidocaine, gamma-aminobutyric acid, or muscimol. Neurons in forelimb areas of both MCx and RN were modulated in advance of forelimb force production. RN neurons more frequently had a phasic discharge pattern, while neurons in MCx more frequently had a tonic pattern. Whereas the modulation of most forelimb area neurons in MCx correlated with responses in a specific direction, the majority of RN neurons were non-directional. Reversible inactivation of CSTc, RN and RST prolonged reaction time. The normal stereotyped form of isometric force trajectories was unaffected by injections at any site. While CSTc inactivation resulted in hypometric responses, response amplitude was unchanged during RN and RST inactivation. We conclude that both MCx and RN contribute to response initiation, but that only MCx is involved in the proper scaling of targeted responses.

Animals↗
PubMed1993

Excitatory amino acids as neurotransmitters of cortical and cerebellar projections to the red nucleus: an immunocytochemical study in the guinea pig.

We combined a retrograde labeling technique with peroxidase immunocytochemistry to verify whether cortical and cerebellar neurons projecting to the red nucleus (RN) contain high concentrations of glutamate and aspartate as possible neurotransmitters. Injections of a tracer, colloidal gold-labeled enzymatically inactive horseradish peroxidase conjugated to wheatgerm agglutinin, into the RN of adult guinea pigs produced retrograde labeling of layer V cortical neurons, with a large predominance in the ipsilateral hemisphere. Corticorubral neurons were located in the granular parietal cortex (Gr), agranular frontal cortex (Ag), agranular cingulate cortex (Cg), and retrobulbar cortex (Rb). Large numbers of retrogradely labeled neurons were concentrated in contralateral interpositus and dentate cerebellar nuclei. We found the majority of corticorubral neurons to be immunostained by antibodies raised in rabbits against glutamate or aspartate conjugated to invertebrate hemocyanin by glutaraldehyde, supporting the hypothesis that excitatory amino acids are neurotransmitters of corticorubral projections. With either antiserum, immunostaining was found in 58-72% of corticorubral neurons in Ag and Gr; higher percentages were observed in Rb (80-85%) and Cg (up to 96%). Cross-sectional area measurements indicated that the perikarya of corticorubral neurons were larger in Ag and Gr than in Rb and Cg; in each area, soma size values of immunopositive corticorubral neurons tended to be larger than those of immunonegative ones. In the cerebellar nuclei, virtually all retrogradely labeled neurons were immunostained by glutamate and aspartate antisera, suggesting that excitatory amino acids might also be considered as possible neurotransmitters for cerebellorubral projections.

Afferent Pathways↗
PubMed1998

Distribution and characteristics of poststimulus effects in proximal and distal forelimb muscles from red nucleus in the monkey.

We used stimulus-triggered averaging (StTA) of electromyographic (EMG) activity to investigate two major questions concerning the functional organization of the magnocellular red nucleus (RNm) for reaching movements in the macaque monkey. The first is whether the clear preference toward facilitation of extensor muscles we have reported in previous studies for distal (wrist and digit) forelimb muscles also exists for proximal muscles (shoulder and elbow). The second question is whether distal and proximal muscles may be cofacilitated from RNm suggesting the representation of functional muscle synergies for coordinated reaching movements. Two monkeys were trained to perform a prehension task requiring multijoint coordination of the forelimb. EMG activity was recorded from 24 forelimb muscles including 5 shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles. Microstimulation (20 microA at 20 Hz) was delivered throughout the movement task. From 137 microstimulation sites in the RNm, a total of 977 poststimulus effects was obtained including 733 poststimulus facilitation effects (PStF) and 244 poststimulus suppression effects (PStS). Of the PStF effects, 58% were obtained from distal muscles; 42% from proximal muscles. Digit muscles were more frequently facilitated (35%) than the wrist, elbow, or shoulder muscles (20, 24, and 18%, respectively). The intrinsic hand muscles were infrequently facilitated (3%). At all joints tested, PStF was more common in extensor muscles than flexor muscles. This extensor preference was very strong for shoulder (85%), wrist (85%), and digit muscles (94%) and weaker for elbow muscles (60%). Of the PStS effects, 65% were in distal muscles and 35% in proximal muscles. Interestingly, the flexor muscles were more frequently inhibited from RNm than extensor muscles. At 72% of stimulation sites, at least two muscles were facilitated. The majority of these sites (61%) cofacilitated both proximal and distal muscles. At the remaining sites (39%), PStF was observed in either the proximal (17%) or distal muscles (22%). Facilitation most often involved combinations of shoulder, elbow, and distal muscles (30%) or shoulder and distal muscles (26%). Only rarely were intrinsic hand muscles part of the total muscle synergy. Our results show that the RNm 1) controls both proximal and distal muscles but the strength of influence is biased toward distal muscles, 2) preferentially controls extensor muscles not only at distal forelimb joints but also at proximal joints, and 3) output zones cofacilitate synergies of proximal and distal muscles involved in the control of forelimb reaching movements.

Animals↗
PubMed1982

A quantitative study of synaptic reorganization in red nucleus neurons after lesion of the nucleus interpositus of the cat: an electron microscopic study involving intracellular injection of horseradish peroxidase.

A quantitative electron microscopic analysis of the corticorubral projection was performed in the red nucleus (RN) of adult cats to determine morphological correlates of synaptic reorganization that occur following a lesion of the interpositus nucleus (IP). Corticorubral synaptic endings were identified by lesioning the sensorimotor cortex 2-6 days before electrophysiological experiments. Horseradish peroxidase (HRP) was injected into electrophysiologically identified RN neurons. Sagittal sections 100 micrometers thick were cut and reacted by diaminobenzidine. Sections containing HRP-positive neurons were selected and embedded in Epon. In normal cats, degenerating corticorubral terminals in the RN region frequently made contact with dendritic profiles, having small cross-sections, while a few made contact with somatic profiles. Similar results were obtained when degenerating terminals making contact with HRP-filled dendrites were analyzed. In the experimental animals, the cortical lesion was performed more than 8 weeks after lesion of the IP. In these animals, degenerating corticorubral terminals were frequently found on proximal dendrites and somata in RN region and HRP-positive neurons in contrast to the findings in normal cats. The results indicate that new corticorubral synapses were formed on proximal dendrites and somata of RN neurons as a consequence of IP lesions.

Animals↗
PubMed1996

Noradrenaline modifies the spontaneous spiking activity of red nucleus neurons in the rat by activation of alpha 2- and beta-adrenoceptors.

We have investigated the effects of noradrenaline (NA) on the spontaneous firing activity of red nucleus (RN) neurons recorded extracellularly in anesthetized rats by using an in vivo electrophysiological technique. Microiontophoretic applications of NA (5-100 nA for 30 s) modified the background firing rate in 99 out of 124 neurons and three different patterns of response were observed in distinct cells. In 61% of the responding neurons NA decreased the mean firing rate, whereas 22% of the neurons responded to NA application with an increase of their spiking activity; in a smaller group of cells (17%) NA exerted a biphasic inhibitory/excitatory effect on the spontaneous firing rate. The effects of NA were reversible and dose-dependent. From histological examination, the neurons responding to NA with a purely inhibitory effect were scattered throughout the RN. On the other hand, the neurons responding to NA with an excitation were found to be more numerous in the dorso-medial part of the RN, whereas the neurons in which NA induced biphasic effects appeared to be segregated in the outer lateral portion of the RN. The alpha 2-adrenoceptor antagonist yohimbine completely blocked the inhibitory effect of NA but was unable to antagonize the excitatory response. In addition, the inhibitory effect of NA was mimicked by clonidine, a selective agonist of alpha 2-adrenoceptors; clonidine had no effect on those cells which responded to NA with an increase of the mean firing rate. The excitatory effect of NA was mimicked by the beta-receptor agonist isoprenaline and was antagonized by timolol, a selective antagonist of beta-adrenoceptors. Isoprenaline was ineffective in those cells in which NA exerted inhibitory responses. Taken together, our results indicate that the inhibitory effect of NA on the firing activity of rat RN neurons were mediated by alpha 2-adrenoceptors, whereas beta-adrenoceptors were responsible for the excitatory effects.

Action Potentials↗