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PubMed1987

Further studies on the use of the fluorescent tracers fast blue and diamidino yellow: effective uptake area and cellular storage sites.

Some basic methodological issues concerning the use of the fluorescent tracers Fast blue (FB) and Diamidino yellow (DY) were studied using the projections of the red nucleus to the nucleus interpositus anterior (NIA) of the cerebellum of the cat. On standard Nissl-stained sections, it was possible to delineate 4 distinct zones at the FB and DY injection sites. Correlative studies of injection sites in the NIA and retrograde labeling of cell bodies in the contralateral red nucleus showed that effective uptake occurred only from the zone mechanically damaged by the injection needle (termed zone 0). The tracer remains in this zone during the post-injection survival. The limited uptake area for both tracers is a valuable feature for studies of restricted neuronal projections. However, the tracers are not suitable for use in quantitative studies, especially those concerning axonal collateralization. Perfusion with water-soluble fixatives did not alter the cellular storage site. In double-labeling experiments using horseradish peroxidase and DY, the HRP histochemistry induced an important "washing out" of DY and consequently, an underestimation of the number of labeled neurons.

Amidines↗
PubMed1988

Inhibition of rubral neurons by a specific ligand for sigma receptors.

1,3-Di-ortho-tolylguanidine (DTG), a compound with marked selectivity for sigma receptors was iontophoretically applied to neurons in the red nucleus and nearby mesencephalic reticular formation. Spontaneous firing of rubral neurons was reduced by DTG in most cases. However, in the reticular formation, less than half of the cells tested showed inhibition; the remaining cells showed either an increase in rate or no consistent response to DTG. This corresponds to the greater density of sigma receptors in the red nucleus and supports previous work which suggests that sigma receptors play a role in the regulation of movement and posture.

Action Potentials↗
PubMed1986

The cerebellorubral projection in the rat: retrograde anatomical study.

The cerebellorubral projections have been studied in the rat using the retrograde transport of horseradish peroxidase-wheat germ agglutinin conjugate. The lateral cerebellar nucleus projects to the parvocellular red nucleus (RN), the anterior (NIA) and posterior (NIP) interposed nuclei project to the magnocellular RN. Whereas the projections from the NIP are limited to the medial aspect of the RN, those from the NIA extend throughout the magnocellular RN. NIA-RN projections are topographically arranged: the medial NIA projects ventrally, the lateral NIA projects dorsally. Functionally, this differential distribution seems to fit the hindlimb-forelimb areas of origin of the rubrospinal tract.

Animals↗
PubMed1979

Observations on the orthograde and retrograde transport of horseradish peroxidase in the cat.

Horseradish peroxidase (HRP) was applied to the precruciate cortex of the cat. The peroxidase was either applied directly to the surface or injected by glass micropipettes in single or multiple injections. Retrograde as well orthograde transport was observed by light and electron microscopy in different areas: in the thalamus: the nucleus ventralis lateralis and the nucleus centrum medianum, in the red nucleus and in the spinal cord. The distribution of HRP within the nervous elements of the nuclei: axon terminals and/or perikarya and dendrites, was observed by light and electron microscopy. HRP was present in dendrites and perikarya, indicating retrograde transport, in experiments where damage to the injected nervous tissue could be suspected. However HRP appeared restricted to the nerve endings, indicating orthograde transport, when the damage seemed to be minimal. This effect of injury on retrograde transport of HRP was further confirmed by experiments using bilateral HRP injections and unilateral lesions of the spinal cord to label rubro-spinal cells. Thus retrograde transport of HRP could be induced by lesion in systems where it does not occur normally. The normal intra-axonal transport of HRP appears to be from the perikaryon to the nerve endings. This orthograde transport can be seen under the light microscope and can be confused with faint retrograde labeling.

Animals↗
PubMed2001

Localization of Claude's syndrome.

Although the red nucleus often has been suggested to be the lesion site responsible for Claude's syndrome, the precise localization of the syndrome is uncertain. Lesion sites were reviewed in six patients with Claude's syndrome and compared with other patients with the syndrome identified by a literature search. The findings strongly suggest that Claude's syndrome occurs because of a lesion of the superior cerebellar peduncle just below and medial to the red nucleus. Midbrain infarction and partial oculomotor nerve palsy was common.

Adult↗
PubMed1999

The effect of rubrospinal tractotomy on a conditioned limb response in the cat.

Five cats were trained to perform a forelimb conditioned response to a paired tone CS/shock UCS. Rubrospinal tract section ipsilateral to the trained limb was carried out following criterion CR performance. Lesion sites were identified histologically and further confirmed by observation of cellular changes in the red nucleus contralateral to the trained limb. Tractotomy resulted in total or near-total loss of the CR. Prolonged postoperative training resulted in no increase in CR performance levels. The UCR remained unaffected, as did limb placing, accuracy of striking at moving objects, grooming, running and walking. Training of the opposite limb in two subjects resulted in mean scores of 90 and 85% within three sessions. Control lesions in those subjects resulted in no changes in CR performance scores. The red nucleus receives a substantial input from sensorimotor cortex and cerebellum, both of which have been shown to represent essential parts of the brain circuitry involved in associative learning and memory. Since pyramidotomy has no effect on limb CR performance [Vonedia TJ. Exp Neurol 1976;19:483-493], the possible role of the red nucleus/rubrospinal tract is discussed in terms of a critical trigger area for the expression of a learned motor response.

Animals↗
PubMed1988

Ultrastructural evidence for direct monosynaptic rubrospinal connections to motoneurons in Macaca mulatta.

The magnocellularis division of the red nucleus of the Macaca mulatta, a midbrain structure involved in processing motor information, is known by light microscopic analysis to project, via the rubrospinal tract, to the contralateral intermediate horn of the spinal cord. Physiological studies, however, provide additional evidence for direct monosynaptic connections to motoneurons subserving distal musculature. This electron microscopic study demonstrates, by analyzing the anterograde transport of 5% wheatgerm agglutinin-horseradish peroxidase injected into the red nucleus, the presence of labeled terminals synapsing upon somata and proximal dendrites of motoneurons in the lateral portion of the ventral horn of the cervical enlargement of the spinal cord. We conclude that this anatomical evidence confirms the presence of direct monosynaptic connections to spinal motoneurons in the primate.

Animals↗
PubMedDate not supplied

Iontophoretic effects of sigma ligands on rubral neurons in the rat.

Iontophoretic application of the sigma ligands, 1,3-di-o-tolylguanidine (DTG), dextrallorphan, and (+)-pentazocine reliably inhibited the firing rate of rubral neurons. Dextrallorphan inhibited 87% of the neurons tested, DTG inhibited 76%, and (+)-pentazocine inhibited 50%. These inhibitions were current dependent and occurred without significant changes in spike amplitude or duration, suggesting that local anesthetic effects were not involved. In contrast to the other sigma ligands, iontophoretic application of (+)-3-PPP in the rat red nucleus resulted in very few inhibitions and tended to elicit weak excitations instead. Only 14% of rubral neurons were inhibited by (+)-3PPP, while 36% were excited. Although unusual, (+)-3-PPP has atypical effects when compared to other sigma ligands in numerous functional assays for sigma receptor activity. (+)-3-PPP, therefore, appears to have complex effects and may act through nonsigma mechanisms or through a different type of sigma binding site than the other compounds. The inhibition of firing rate produced by the more typical sigma ligands may contribute to the postural changes produced by microinjection of sigma ligands into the rat red nucleus.

Animals↗
PubMed1995

Effect of zolpidem on gamma-aminobutyric acid (GABA)-induced inhibition predicts the interaction of ethanol with GABA on individual neurons in several rat brain regions.

Previous investigations have suggested a relationship between zolpidem binding within specific brain regions and the ability of ethanol or zolpidem to enhance gamma-aminobutyric acid (GABA)-induced inhibition. The purpose of the present study was to extend our electrophysiological analysis to additional brain sites with high levels of zolpidem binding. In the brain regions chosen, red nucleus and globus pallidus, GABA-induced inhibition was shown to be enhanced by either ethanol or zolpidem on some, but not all, neurons. These findings led to the hypothesis that the effect of zolpidem on GABA-induced inhibition would predict the action of ethanol on responses to GABA for that neuron. When zolpidem and ethanol were applied individually to the same neurons in the red nucleus and globus pallidus, those neurons sensitive to zolpidem enhancement of GABA also were sensitive to ethanol. Conversely, if zolpidem did not enhance responses to GABA, ethanol did not enhance responses to GABA at these brain sites. A similar relationship between the abilities of zolpidem and ethanol to enhance GABA-induced inhibition was obtained in 90% of the neurons studied in the medial septum/diagonal band and ventral pallidum. These studies provide further support for the contention that the zolpidem-sensitive GABAA-benzodiazepine isoreceptor also responds to ethanol. Finally, the expression of GABAA subunit mRNAs was analyzed by polymerase chain reaction from micropunches of several brain regions that contain zolpidem binding sites and exhibit sensitivity to ethanol. Polymerase chain reaction analysis proved more sensitive than in situ hybridization in the detection of receptor subunit mRNAs. Several subunits (alpha 1, alpha 2, alpha 3, beta 2, beta 3 and gamma 2) were common to all brain regions in which ethanol and zolpidem enhanced GABA responses. GABAA receptor alpha 4/5, alpha 6, beta 1, gamma 1, gamma 3 and delta subunits were not consistently expressed in association with the presence of zolpidem binding. These data are consistent with the view that one native GABAA receptor to which zolpidem binds, and on which ethanol acts, contains the GABAA receptor subunits alpha 1, beta 2 and gamma 2; however, the present investigation did not preclude the possibility that other subunit combinations can contribute to ethanol and zolpidem enhancement of responses to GABA.

Animals↗
PubMed1981

An electron microscopic study of the afferent connections of the lateral reticular nucleus of the cat.

The mode and pattern of termination of the afferents to the lateral reticular nucleus (LRN) of the cat were examined at the cellular level through the ultrastructural localization of induced degeneration. Examination of the LRN following hemicordotomy at the fifth and sixth cervical levels revealed that most of the degenerating terminals were in contact with intermediate and distal dendrites, and that most of these degenerating terminals were small and contained round vesicles. Fewer degenerating terminals were observed on the somata and proximal dendrites after spinal hemisection, and most of these terminals were large and contained round vesicles. Following lesions of the pericruciate cortex, small degenerating terminals were occasionally observed making contact onto intermediate and distal dendrites. Degenerating rubral terminals were observed synapsing on somata, somatic and dendritic spines, proximal dendrites and most commonly on intermediate and distal dendrites following lesioning of the red nucleus. The degenerating axosomatic rubro-LRN terminals belonged to the large, round-vesicle terminal population, while those degenerating terminals contacting intermediate and distal dendrites belonged to the small, round-vesicle population. Small, degenerating terminals were occasionally seen following lesions of the fastigial nucleus, and they made synaptic contact mainly onto intermediate and distal dendrites and dendritic spines. The present ultrastructural observations taken together with the convergence pattern of LRN afferents and the available electrophysiological data on inputs to the LRN suggest an extensive integration of converging impulses from two or more afferent sources to the rostral LRN neurons. The results of this study therefore support the veiw that the rostral LRN functions as a comparator of command signals from the motor cortex and red nucleus and feedback signals from the spinal cord and cerebellum during ongoing movement.

Afferent Pathways↗
PubMed1981

Descending projections from brainstem and sensorimotor cortex to spinal enlargements in the cat. Single and double retrograde tracer studies.

Single and double retrograde tracer techniques were employed in cats to investigate: (1) the topographical relationships between supraspinal neurons projecting to either the brachial or lumbosacral enlargement, (2) the distribution and relative frequency of single supraspinal neurons which project to both enlargements by means of axonal branching. In one group of cats large injections of horseradish peroxidase (HRP) were made throughout either the brachial or lumbosacral enlargement. The results from these experiments support recent observations on the multiplicity of brainstem centers giving origin to descending spinal pathways and provide evidence for a population of corticospinal neurons in area 6. In a second set of experiments, HRP was injected in one enlargement, and 3H-apo-HRP (enzymatically inactive) was injected in the other enlargement. Relatively large numbers of neurons with collateral projections to both enlargements (double-labeled) were observed in the medullary and pontine reticular formation, the medial and inferior vestibular nuclei bilaterally, the ipsilateral lateral vestibular nucleus, Edinger-Westphal nucleus, caudal midline raphe nuclei and nuclear regions surrounding the brachium conjunctivum. By contrast, double-labeled neurons were infrequently observed in the red nucleus and sensorimotor cortex, contralateral to the injections. In the red nucleus, lateral vestibular nucleus and sensorimotor cortex, neurons projecting to the brachial enlargement were largely segregated topographically from neurons projecting to the lumbosacral enlargement. However, there was some overlap, and double-labeled neurons were consistently observed within the region of overlap. In the sensorimotor cortex, the overlap between brachial- and lumbar-projecting neurons was most prominent in areas 4 and 3a, along the cruciate sulcus, but also involved other cytoarchitectonic regions in the medial aspect of the hemisphere.

Animals↗
PubMed1991

GABAergic control of rubral single unit activity during a reaction time task.

The activity of 61 rubral neurones was recorded in association with microinjections of GABA, muscimol, bicuculline-methiodide or saline, in cat Red Nucleus area, during the performance of a reaction time task. The depressing action of GABA and muscimol on the firing of most neurones (17/23) suggests that, in a behavioural situation, an inhibitory GABAergic control can be exerted on rubral neurones discharging with different patterns during the reaction time task. The motor slowing down induced by GABA and muscimol is in agreement with a general reduction of the rubral output. Injections of bicuculline, whose antagonistic effects on GABA transmission are well established in the Red Nucleus, had various consequences on the firing of rubral neurones: 1) the decreases of activity related to the reaction time task were never suppressed, suggesting that these task-related inactivations are probably not mediated by GABA A receptors; 2) an enhancement of the tonic and phasic discharges was found for 1/4 of the neurones (7/29), which were either activated or not modulated in relation to the reaction time task, suggesting that a sustained GABA A-mediated inhibition, blocked by bicuculline, could be exerted on these neurones; 3) a reduction of the tonic and phasic discharges was observed for other neurones (15/29), which were either activated, inactivated or not modulated in relation to the reaction time task, suggesting that the activity of these neurones could be controlled by inhibitory processes not mediated by GABA A receptors, possibly enhanced or released by bicuculline. The delay in motor triggering induced by bicuculline could be related to the disruption of the pattern or rubral output during the reaction time task, as a result of the opposite changes affecting the firing of rubral neurones. A well-balanced GABAergic activity appears to be critical in the control of rubral firing during the performance of the reaction time task.

Animals↗
PubMed1995

A time-dependent loss of retrograde transport ability in distally axotomized rubrospinal neurons.

Studies on the effect of axotomy on adult intrinsic central projection neurons have generally assumed that the severed proximal axonal stumps were still capable of retrogradely transporting tracer at varying times after injury. Failure of transport was interpreted as neuronal death, which is at odds with current understanding that central projection neurons survived distal axotomy. We used lumbar spinal cord-projecting rubrospinal neurons of the rat as a model to evaluate the ability of injured neurons to transport tracer retrogradely at different times after distal axotomy. We examined only the caudal part of the red nucleus, since rubrospinal neurons are concentrated here. In control animals, tracer applied to the rubrospinal tract at the T10 vertebral level labeled ventrolateral rubral neurons, while C3 application marked all rubral neurons. From 3 days after a T10 axotomy and tracer application, most ventrolateral neurons were no longer labeled by another tracer application at the C3 vertebral level via an axonal cut. The phenomenon was not caused by tracer toxicity, since a T10 tractotomy without tracer application also prevented these axotomized neurons from being labeled when treated similarly. Thus, neuronal retrograde transport capability was seriously retarded 3 days after a distal axotomy. Loss of retrograde transport may merely suggest that a mechanism no longer in service has been switched off, or perhaps it may insulate injured neurons from the effect of lesion site-derived factors. Using this property, we were able to localize cervical spinal cord-projecting rubrospinal neurons in the caudal red nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Distribution of effective synaptic currents in cat triceps surae motoneurons. VI. Contralateral pyramidal tract.

We measured the effective synaptic currents (IN) produced by stimulating the contralateral pyramidal tract (PT) in triceps surae motoneurons of the cat. This is an oligosynaptic pathway in the cat that generates both excitation and inhibition in hindlimb motoneurons. We also determined the effect of the PT synaptic input on the discharge rate of some of the motoneurons by inducing repetitive firing with long, injected current pulses during which the PT stimulation was repeated. At resting potential, all but one triceps motoneuron received a net depolarizing effective synaptic current from the PT stimulation. The effective synaptic currents (IN) were much larger in putative type F motoneurons than in putative type S motoneurons [+4.6 +/- 2.9 (SD) nA for type F vs. 0.9 +/- 2.4 nA for putative type S]. When the values of IN at the threshold for repetitive firing were estimated, the distribution was markedly altered. More than 60% of the putative type S motoneurons received a net hyperpolarizing effective synaptic current from the pyramidal tract stimulation as did 33% of the putative type F motoneurons. This distribution pattern is very similar to that observed previously for the effective synaptic currents produced by stimulating the contralateral red nucleus. As would be expected from the wide range of IN values at threshold (-4.8 to +8.7 nA), the PT stimulation produced dramatically different effects on the discharge of different triceps motoneurons. The discharge rates of those motoneurons that received depolarizing effective synaptic currents at threshold were accelerated by PT stimulation (+1 to +8 imp/s), whereas the discharge rates of cells that received hyperpolarizing currents were retarded by the PT input (-2 to -7 imp/s). The change in firing rates produced by the PT stimulation was generally approximated by the product of the effective synaptic currents and the slopes of the motoneurons' frequency-current relations. Our findings indicate that the contralateral pyramidal tract may provide a powerful source of synaptic drive to some high-threshold motoneurons while concurrently inhibiting low-threshold cells. Thus this input system, like that from the contralateral red nucleus, can potentially alter the gain of the input-output function of the motoneuron pool as well as disrupt the normal hierarchy of recruitment thresholds.

Animals↗
PubMed1988

Modifications of brain electrical activity after activation of the benzodiazepine receptor types in rats and rabbits.

The present study reports a comparative electroencephalographic (EEG) study of drugs belonging to different chemical classes which share the property to bind at benzodiazepine (BDZ) recognition sites. The EEG patterns are recorded from the neocortex of rats and rabbits as well as from dorsal hippocampus and red nucleus in rabbits after intravenous administration of diazepam (0.1-10 mg/kg), clonazepam (0.02-2.5 mg/kg), zopiclone (0.3-3 mg/kg), flunitrazepam (0.03-2.5 mg/kg), CGS 9896 (0.1-3 mg/kg), zolpidem (0.1-3 mg/kg) and Cl 218,872 (0.1-10 mg/kg). The most relevant differences are observed at the level of the neocortex. All drugs induced appearance of 7-12 Hz spindle bursts. On the contrary, the presence of 15-30 Hz waves (defined beta-like activity) mainly occurs after diazepam, clonazepam and zopiclone. Scarce beta-like activity is present after CGS 9896, zolpidem and Cl 218,872. According to the selectivity of these drugs for the various types of BDZ receptor, one can speculate that activation of BDZ2 is relevant for the appearance of the beta-like activity. Flunitrazepam, diazepam, and zolpidem increase the amplitude of the red nucleus waves. Such an effect is less marked after zopiclone and CGS 9896, whereas is almost absent after clonazepam and Cl 218,872. A reduction of the frequency is observed after flunitrazepam, diazepam, clonazepam, CGS 9896 and zolpidem, whereas it is almost absent after zopiclone and Cl 218,872. Finally, all drugs induce a reduction of the amplitude of the hippocampal theta rhythms, whereas after diazepam, flunitrazepam, zolpidem and CGS 9896 a slowing of the record also occurs.

Animals↗
PubMed1975

Effects of afferent volleys from the limbs on the discharge patterns of interpositus neurones in cats anaesthetized with alpha-chloralose.

1. In cats anaesthetized with alpha-chloralose, micro-electrodes have been used to record the discharge patterns of single neurones in the region of the nucleus interpositus. 2. Almost all cells tested could be antidromically invaded following electrical stimulation of the contralateral red nucleus, showing that they were cerebellar efferent neurones. 3. A little over half of the interpositus neurones were spontaneously active, usually at rates of less than 20 impulses/sec. 4. About 40% of the cells had no spontaneous activity, although they gave brisk responses to electrical stimulation of cutaneous nerves. Such silent units were encountered most frequently in the earlier stages of an experiment, but a number were found more than 15 hr after the beginning of an experiment. 5. Stimulation of cutaneous and mixed nerves of the fore and hind limbs provoked impulse discharges of the cells and also produced phases of deceleration of the resting discharge of spontaneously firing cells. 6. The typical response of an interpositus neurone consisted of a short latency (6-35 msec) discharge, usually separated from a long latency (50-500 msec) discharge by a period of inhibition or return to the resting discharge rate. The two phases of excitation appeared to be independently generated, since in a number of cells one phase appeared without the other. In addition, the later phase of excitation was abolished in all cells tested by a small dose of pentobarbitone which produced very little effect on the earlier phase. The long latency response was quantitatively much greater, sometimes consisting of 50 or more impulses in a response which lasted several hundred msec, but was very variable from one trial to another. 7. The long latency discharge and sometimes the preceding inhibition could readily be mimicked by single shock stimulation of the region of the contralateral inferior olive. Short latency discharges were, however, rarely evoked by olivary stimulation. 8. It is suggested that the short latency responses of the interpositus neurones were a result of synaptic excitation via cerebellar afferents, while the ensuing inhibition was a result of post-synaptic inhibition resulting from the Purkinje cell excitation due to the afferent volleys. It is suggested that the long latency excitation is due to the afferent volleys. It is suggested that the long latency excitation is due at least in part to disinhibition resulting from long pauses in Purkinje cell firing following their activation by climbing fibre afferents. 9. The possibility that these long latency responses have a physiological significance in relation to locomotion is discussed.

Action Potentials↗
PubMed2000

[A comparative analysis of the descending projections of areas 5 and 7 of the parietal cortex to the cat brain stem].

Relative quantity of descending fibres of parietal fields 5 and 7 of cat brain stem was studied. Maximal projections of these field were determined, maximal projections of fields 5 and 7 to red nucleus reticular nucleus of midbrain and nucleus proprius of pons were shown. Topographic and quantitative overlapping of projections of fields 5 and 7 in red nucleus and reticular nucleus of midbrain was noted. Field 5 is maximally presented in ventral nucleus while field 7 has maximal number of projections in lateral nucleus. Projection of fields 5 an 7 to superior colliculus of tectum of the midbrain was determined that was significant although less pronounced than in the above mentioned nuclei. The number of fibres projecting onto the superior colliculus of tectum of the midbrain (its caudal part) from field 7 exceeds that from field 5. There are less fibres in inferior colliculus of tectum of the midbrain than in superior colliculus. The number of fibres projecting from field 5 is greater than those from field 7 in inferior colliculus. In caudal reticular nucleus of pons the presence of fields 5 and 7 was not significant. Comparison of the authors' data with that available in literature allows to suggest the possible inhibitory, i.e. modulating influence of parietal cortex on nuclei of the pons.

Animals↗
PubMed1990

Metabolites of haloperidol display preferential activity at sigma receptors compared to dopamine D-2 receptors.

Haloperidol bound with equal affinity to sigma and dopamine D-2 receptors (KI = 2.8 nM). Compared to haloperidol, its carbonyl-reduced metabolite bound to sigma receptors with nearly equal affinity. However, reduced haloperidol bound to dopamine receptors with 85-fold lower affinity compared to haloperidol (KI = 239 nM). The chlorophenyl-hydroxy-piperidine metabolite of haloperidol lacked affinity for dopamine receptors, but bound with moderate affinity to sigma receptors (KI = 326 nM). The carboxylic acid metabolite lacked affinity for either receptor. Like haloperidol, (+)-pentazocine, and 1,3-di-o-tolylguanidine, reduced haloperidol potently inhibited the phosphoinositide response to muscarinic agonists in rat brain synaptoneurosomes, an assay which monitors sigma agonist activity. This metabolite also produced a dystonic alteration of head position in rats when microinjected into the red nucleus. However, unlike observations with haloperidol and other sigma ligands, this effect was associated with pathological changes in the red nucleus. Therefore, it cannot be attributed to sigma receptor interactions with certainty. These findings suggest that administration of haloperidol results initially in effects mediated through both dopamine and sigma receptors, but as metabolism proceeds the sigma actions would be expected to decline at a significantly slower rate than the dopaminergic actions.

Animals↗