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PubMed1975

Input-output relations of the red nucleus in the cat.

In unanesthetized cats, microstimulation within the red nucleus produces contraction of single muscles of the contralateral limbs and face. Separate zones may activate different muscles. Forelimb muscles were primarily activated from areas in the dorsomedial quadrants of the red nucleus whereas hindlimb muscles were predominantly activated from the ventorlateral quadrants. With stimulus currents of 10 muA there was considerable overlap in the effective zones activating different muscles. In the majority of cases the minimal threshold was under 10 muA when stimilating with a 50-msec pulse train. Current thresholds for electromypgraphic changes in the muscles varied inversely with pulse frequency and train duration. When long stimulus trains were applied to the red nucleus, the resulting muscle contraction was sustained for the duration of the stimulus. These motor effects did not depend upon the motor cortex or pyramidal tract but were mediated by a tract in contralateral dorsal quadrants of the spinal cord which was likely to be the rubrospinal tract. Units within the red nucleus typically had wide cutaneous receptive fields and responded to deep pressure and joint rotation in one or more limbs. Usually the focus driving the cell most briskly was located in one of the contralateral limbs and corresponded to the limb where muscle contraction was elicited by microstimulation with the same electrode. It is concluded that the red nucleus includes overlapping efferent neuronal colonies controlling individual muscles irrespective of their functional class. This property is shared by the motor cortex and suggests that these two structures may complement each other in the control of movement. The more diffuse activation of rubral than cortical neurons by natural stimuli suggests that rubral activity may not be as tightly linked as that of the motor cortex to specific peripheral input.

Animals↗
PubMed1991

Role of excitatory amino acids in mediating burst discharge of red nucleus neurons in the in vitro turtle brain stem-cerebellum.

1. Bursts of discharge have been recorded in the red nucleus in several species and are thought to represent the expression of motor commands. A cerebellorubral circuit comprised of recurrent connections among the cerebellum, red nucleus, and reticular formation was postulated to function as a positive feedback loop that generates these motor commands and transmits them to the spinal cord via the rubrospinal pathway. We have used an in vitro preparation from the turtle that leaves the circuitry connecting the cerebellum, brain stem, and spinal cord intact to study the role of excitatory amino acid neurotransmitters and recurrent excitation in mediating the generation of burst discharges in the red nucleus. 2. Burst discharges were recorded extracellularly from single cells in the red nucleus in response to single pulse or brief train stimulation of the contralateral spinal cord or brief train stimuli applied to the ipsilateral cerebellar cortex. The firing characteristics and pharmacologic sensitivities of the bursts were independent of the type of stimulus used. The bursts had long durations ranging from 2 to 17 s and showed spike frequency adaptation. 3. Transection of the cerebellar peduncle, which eliminates inhibition impinging onto the cerebellorubral circuit, greatly enhanced the spontaneous activity and burst discharges recorded in the contralateral red nucleus. Furthermore, bath application of a solution containing elevated levels of calcium and magnesium blocked the expression of burst discharges even though synaptic activation of the neurons was not blocked. 4. The possibility that excitatory amino acid receptors mediate burst responses in the red nucleus was investigated in light of the antagonistic effects of elevated magnesium ions on bursting. Bath application of 100 microns DL-2-amino-5-phosphonovaleric acid (APV), a specific N-methyl-D-aspartate (NMDA) receptor antagonist; [10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)], a specific non-NMDA receptor antagonist; or 100 microM, DL-2-amino-4-phosphonobutyric acid (AP4), an agonist of a fourth class of excitatory amino acid receptor, blocked burst activity in the red nucleus. With a multibarreled pipette for simultaneous ejection of drug and recording, iontophoresis of APV or CNQX into the red nucleus blocked bursting whereas AP4 failed to show a significant effect. These data suggest that red nucleus neurons have both NMDA and non-NMDA receptors. The site of action of the AP4-sensitive receptor appears to be elsewhere in the cerebellorubral circuit. 5. Iontophoretic application of excitatory amino acid receptor agonists NMDA and quisqualate (Q) induced excitation of red nucleus neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Evidence for GABAergic interneurons in the red nucleus of the painted turtle.

Immunocytochemical and electrophysiological evidence supporting the presence of GABAergic interneurons in the turtle red nucleus is presented. Injections of HRP into the spinal cord produced labeling of large neurons in the contralateral red nucleus. The peroxidase-antiperoxidase (PAP) method revealed smaller cells immunoreactive to an antibody against glutamate decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter GABA, that were interspersed among larger immunonegative neurons. Similar small neurons were densely immunostained by antibodies to GABA-glutaraldehyde conjugates obtained from different sources and applied according to pre-embedding and postembedding protocols. Rubrospinal neurons retrogradely labeled with HRP measured 16 and 27 microns in mean minor and major cell body diameters, while GABA-like immunopositive neurons situated within the red nucleus measured 7 and 13 microns. There was very little overlap in soma size between the two cell populations. Therefore, we suggest that the GAD- and GABA-positive neurons may be local inhibitory interneurons. This notion is further supported by observations of pre-embedding immunostaining for GAD and postembedding immunostaining for GABA showing that the turtle red nucleus is amply innervated by immunoreactive axon terminals. These puncta are closely apposed to cell bodies and dendrites of both immunonegative large neurons and immunopositive small neurons. Moreover, immunogold staining at the electron microscopic level demonstrated that GABA-like immunoreactive axon terminals with pleomorphic synaptic vesicles formed symmetric synapses with cell bodies and dendrites of the two types of red nucleus cells. These ultrastructural features are commonly assumed to indicate inhibitory synapses. A moderately labeled bouton with round vesicles and asymmetric synapses was also observed. In addition, the two types of red nucleus neurons received asymmetric axosomatic and axodendritic synapses with GABA-negative boutons provided with round vesicles, features usually associated with excitatory functions. To obtain electrophysiological evidence for inhibition, intracellular recordings from red nucleus neurons were conducted using an in vitro brainstem-cerebellum preparation from the turtle. Small, spontaneous IPSPs were recorded from 7 out of 14 red nucleus cells studied. These morphological and physiological results provide strong support for concluding that the turtle red nucleus, like its mammalian counterpart, contains GABAergic inhibitory interneurons. While we have not identified the main source of input to these interneurons, in view of the scarce development of the reptilian cerebral cortex, this input is unlikely to come from the motor cortex as it does in mammals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

The human red nucleus and lateral cerebellum in supporting roles for sensory information processing.

A functional MRI study compared activation in the red nucleus to that in the lateral cerebellar dentate nucleus during passive and active tactile discrimination tasks. The study pursued recent neuroimaging results suggesting that the cerebellum may be more associated with sensory processing than with the control of movement for its own sake. Because the red nucleus interacts closely with the cerebellum, the possibility was examined that activity in red nucleus might also be driven by the requirement for tactile sensory processing with the fingers rather than by finger movement alone. The red and dentate nuclei were about 300% more active (a combination of activation areas and intensities) during passive (non-motor) tactile stimulation when discrimination was required than when it was not. Thus, the red nucleus was activated by purely sensory stimuli even in the absence of the opportunity to coordinate finger movements or to use the sensory cues to guide movement. The red and dentate nuclei were about 70% more active during active tactile tasks when discrimination was required than when it was not (i.e., for simple finger movements alone). Thus, the red nucleus was most active when the fingers were being used for tactile sensory discrimination. In both the passive and active tactile tasks, the observed activation had a contralateralized pattern, with stronger activation in the left red nucleus and right dentate nucleus. Significant covariation was observed between activity in the red nucleus and the contralateral dentate during the discrimination tasks and no significant correlation between the red nucleus and the contralateral dentate activity was detected during the two non-discrimination tasks. The observed interregional covariance and contralateralized activation patterns suggest strong functional connectivity during tactile discrimination tasks. Overall, the pattern of findings suggests that the activity in the red nucleus, as in the lateral cerebellum, is more driven by the requirements for sensory processing than by motor coordination per se.

Adult↗
PubMed1991

Decreased release of D-aspartate in the guinea pig spinal cord after lesions of the red nucleus.

This study attempts to determine if fibers that project from the guinea pig red nucleus to the spinal cord use L-glutamate and/or L-aspartate as transmitters. Unilateral injections of kainic acid were placed stereotaxically in the red nucleus to destroy the cells of origin of the rubrospinal tract. Six days after the injection, Nissl-stained sections through the lesion site showed that the majority of neurons in the red nucleus ipsilateral to the kainic acid injection were destroyed. In addition, the lesioned area included parts of the surrounding midbrain reticular formation. Silver-impregnated, transverse sections of the cervical spinal cord revealed the presence of degenerating fibers contralaterally in laminae IV-VII of the gray matter. Ipsilaterally, very sparse degeneration was evident in laminae VII and VIII of the gray matter. Two to six days after surgery, the electrically evoked, Ca2(+)-dependent release of both D-[3H]aspartate, a marker for glutamatergic/aspartatergic neurons, and gamma-amino[14C]-butyric acid ([14C]GABA) was measured in dissected quadrants of the spinal cervical enlargement. Lesions centered on the red nucleus depressed the release of D-[3H]aspartate by 25-45% in dorsal and ventral quadrants of the cervical enlargement contralaterally. The release of [14C]GABA was depressed by 27% in contralateral ventral quadrants. To assess the contribution of rubro- versus reticulospinal fibers to the deficits in amino acid release, unilateral injections of kainic acid were placed stereotaxically in the midbrain reticular formation lateral to the red nucleus. Nissl-stained sections through the midbrain revealed the presence of extensive neuronal loss in the midbrain and rostral pontine reticular formation, whereas neurons in the red nucleus remained undamaged. In the spinal cord, degenerating axons were present ipsilaterally in laminae VII and VIII of the gray matter. Some fiber degeneration was also evident contralaterally in laminae V and VI of the gray matter. This lesion did not affect the release of either D-[3H]aspartate or [14C]GABA in the spinal cord. The substantial decrements in D-[3H]aspartate release following red nucleus lesions suggests that the synaptic endings of rubrospinal fibers mediate the release of D-[3H]aspartate in the spinal cord. Therefore, these fibers may be glutamatergic and/or aspartatergic. Because other evidence suggests that rubrospinal neurons are probably not GABAergic, the depression of [14C]GABA release probably reflects changes in the activity of spinal interneurons following the loss of rubrospinal input.

Animals↗
PubMed2000

Demonstration of the medullary lamellae of the human red nucleus with high-resolution gradient-echo MR imaging.

BACKGROUND AND PURPOSE: The human red nucleus is not a uniform structure. It is composed of caudally located magnocellular and rostrally located parvicellular subnuclei. In fact, the latter forms the bulk of the human red nucleus and can be subdivided histologically by two medullary lamellae into three parts. Because iron is deposited in the human red nucleus and gradient-echo sequences are more sensitive than spin-echo sequences in the detection of iron, a high-resolution gradient-echo MR sequence was used in this study to determine whether the medullary lamellae of the normal human red nucleus could be detected in vivo. METHODS: Ten healthy volunteers (seven men and three women, 27-48 years old) were examined with a high-resolution T2-weighted gradient-echo MR sequence using a 1.9-T MR imager. The scanning parameters were 60/40/15 (TR/TE/excitations) with a flip angle of 20 degrees , a pixel size of 1 x 1 mm, and a slice thickness of 5 mm. RESULTS: The medullary lamellae were depicted in all subjects in three imaging planes: coronal, oblique axial, and oblique sagittal. The signal intensity of the lamellae was consistently higher than that of other parts of the red nucleus on all images. With the lamellae, the parvicellular subnucleus of the human red nucleus can be divided into its subdivisions. CONCLUSION: High-resolution gradient-echo MR imaging is capable of depicting the medullary lamellae of the normal human red nucleus in vivo.

Adult↗
PubMed1988

Classical conditioning does not occur when direct stimulation of the red nucleus or cerebellar nuclei is the unconditioned stimulus.

The involvement of the cerebellum and the red nucleus in the classically conditioned nictitating membrane/eyeblink response in the rabbit is investigated using direct stimulation of the interpositus or the red nucleus as the unconditioned stimulus. Stimulation of either of these structures produced eye closure in naive animals, and this eye closure was paired with a tone in the standard Pavlovian conditioning paradigm. The results indicate that eyelid closure due to stimulation of either the red nucleus or the interpositus nucleus is not sufficient for the development of conditioned responses to the tone. Animals which had received interpositus stimulation as the unconditioned stimulus acquired the conditioned response to tone significantly faster following the substitution of air puff for stimulation than did those animals that had received red nucleus stimulation, or controls that did not receive any stimulation. However, animals that had been trained to tone-air puff could not retain the conditioned response after being switched to tone-interpositus stimulation. Lesions of the interpositus and the red nucleus through the stimulating electrodes were effective in impairing or abolishing conditioned responses. The results are interpreted to indicate that the red nucleus and interpositus are elements of the circuit that carries out the expression of the conditioned response. In addition the interpositus, but not the red nucleus, may be critical in the formation of the memory trace for the conditioned stimulus-unconditioned stimulus association, by virtue of the greatly accelerated learning that results from its stimulation.

Animals↗
PubMed1997

A hypothalamic projection to the turtle red nucleus: an anterograde and retrograde tracing study.

It is well known that the reptilian red nucleus lacks a descending motor cortical input to the red nucleus, but has a well-developed cerebellar input. The present study was undertaken to determine whether there is a descending rubral input that originates from the hypothalamus. Using an in vitro preparation from the turtle, injections of neurobiotin into the red nucleus resulted in retrograde labeling of neurons in the suprapeduncular nucleus of the hypothalamus. Injections of either neurobiotin or fluorescein dextran into the suprapeduncular nucleus resulted in anterograde labeling of axons and terminal boutons in the red nucleus. The majority of these terminations appeared to lie in the medial part of the red nucleus. These data have implications for the potential control of the somatic motor system of reptiles by limbic system inputs.

Animals↗
PubMed2006

Conventional MRI is inadequate to delineate the relationship between the red nucleus and subthalamic nucleus in Parkinson's disease.

BACKGROUND: An understanding of the relationships between the anterior commissure-posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus (RN) is imperative if these structures are to be used for targeting in deep brain stimulation. Currently, these relationships are incompletely understood and difficult to assess using conventional MRI. We examined the location and relationships of the STN and the RN to the AC-PC line and to each other in order to provide a greater understanding of their utility when targeting the STN, and the consistency of these anatomic relationships when examined using conventional MRI. METHODS: A total of 52 STN and RN in 26 patients with Parkinson's disease were evaluated on T2-weighted MR images. The anterior and posterior commissures and the border coordinates of the STN and RN were derived using frame coordinates. The distances from the midcommissural point (mcp) to the centers of the STN and RN, the diameters for each nucleus, and the distances between the nuclei were calculated in the x-, y-, and z-axes. RESULTS: The mean AC-PC length was 26.1 +/- 1.3 mm. The distance from the mcp to the center of the STN was 10 +/- 0.7 mm in the x-axis, 0.2 +/- 0.7 mm in the y-axis, and 3.3 +/- 0.9 mm in the z-axis. The distance from the mcp to the center of the RN was 4.7 +/- 0.6 mm in the x-axis, -5.9 +/- 1.0 mm in the y-axis, and 6.1 +/- 1.3 mm in the z-axis. The distance between the STN and RN was 2.3 +/- 0.7 mm in the x-axis, 2.1 +/- 1.0 mm in the y-axis, and -0.2 +/- 1.3 mm in the z-axis. CONCLUSIONS: Although recent studies imply that the RN can be used as a relatively consistent marker for the position of the STN, the present data suggest otherwise. These data indicate that a single targeting method may be inadequate given the resolution of conventional MRI, and that it is imperative to use multiple anatomical measurements when targeting the STN for deep brain stimulation in Parkinson's disease.

Deep Brain Stimulation↗
PubMed1990

Red nucleus lesions do not affect limb preference or use, but exacerbate the effects of motor cortex lesions on grasping in the rat.

The corticospinal and rubrospinal systems are thought to collaborate in the production of skilled forelimb movements in primates. This study examined whether this relation holds in rodents. Limb preference and limb skill were assessed in a reaching-for-food task in rats with ibotenic acid lesions of the red nucleus or combined red nucleus lesions and aspirative motor cortex lesions. Major findings were: (1) Unilateral red nucleus lesions did not influence subsequent development of limb preference in naive rats. (2) Unilateral red nucleus lesions in pretrained rats failed to affect the incidence of reaching (total reaches) and reaching success (hit percent) by either the contralateral or ipsilateral limb. (3) Whereas motor cortex lesions impaired subsequent use of the contralateral limb, additional red nucleus lesions did not change total reaches or hit percent, but did produce moderate qualitative changes in limb accuracy and paw opening during grasping. The results demonstrate that in the rat, the red nucleus is not essential for the ballistic component of reaching but may contribute to fine motor control.

Animals↗
PubMed1988

[Reorganization of the synaptic inputs of the sensorimotor cortex to the red nucleus after the destruction of the cerebellar nucleus interpositus in adult cats].

Responses of the red nucleus to neurons to stimulation of the ipsilateral sensorimotor cortex have been studied in acute cats with preliminary lesion of the contralateral cerebellar nucleus interpositus (exposition from two weeks to a year and longer period) by intracellular recording technique. Acceleration of the monosynaptic EPSPs rise testifying to formation of the terminal dendrosomatic sprouting of axons of the corticorubral neurons on proximal segments of the somatodendritic membrane of the red nucleus neurons was observed. Various division of the sensorimotor cortex were unequally involved in the process of reorganization of synaptic inputs on the level of individual red nucleus neurons.

Animals↗
PubMed1982

[Reorganization of the synapsoarchitectonics of the rat red nucleus after destruction of the motor cortex of the cerebral hemispheres].

In 50 white rats the red nucleus synaptic organization both normal and at various time (1, 2, 3, 5, 7, 10, 14, 21, 30 and 60 days) after destruction of the cerebral cortical motor area has been studied electron microscopically. Peculiarities of the synaptic organization in the parvicellular and macrocellular parts of the red nucleus and reorganization of the synapsoarchitectonics are demonstrated after the motor cortex has been destroyed. During the first 2-3 weeks after the destruction, certain degenerative changes are mainly noted in the parvicellular area of the red nucleus. Small axonal terminals with round light synaptic vesicles are subjected to degeneration according to the dark type, they form asymmetric synapses on small, sometimes--on middle dentritic branches. On the 21-30th day, together with the degenerative changes, plastic reorganization of the red nucleus synapsoarchitectonics both in the parvicellular area and in the macrocellular areas adjoining the latter are noted. Evidently, this reorganization takes place at the expense of the cerebello-rubral fibres. The participation of the inter-posito-rubral fibres terminating in the macrocellular part of the red nucleus is definitely stated. Their large terminals form synapses on the soma and the proximal dendrites of the giant and large neurons. It is from these axonal terminals that the growth cones take their origin on the 21st day after the destruction of the motor cortex. Later (on the 30th and the 60th day) new processes and synapses appear in the parvicellular part of the red nucleus. Some dendrites undergo certain changes. Dendro-dendritic synapses and complex synaptic contacts appear.

Animals↗
PubMed2001

Differential expression of calcium-binding proteins in the red nucleus of the developing and adult human brain.

The adult human red nucleus consists of two parts: (1) the parvocellular part, which is clearly separated from (2) the magnocellular part. The latter and its rubrospinal projection is known to be rudimentary in the adult human brain. Information concerning the fetal or neonatal features of the red nucleus is sparse. This study is aimed at providing a detailed account of the distribution of three calcium-binding proteins: calretinin (CR), calbindin (CB), and parvalbumin (PV), which are known to be expressed in distinct neuronal populations. Special attention has been paid to transient phenomena. CB was the most abundant protein in the magnocellular part in fetal and perinatal brains; immunoreactive (ir) neurons appeared numerous and densely packed. In the adult only few and widely spaced ir nerve cells were present. CR-expression largely corresponds to that of CB, except that fewer neurons were immunolabelled. In double-labellings the majority of neurons expressed both CB and CR; a moderate number of nerve cells solely expressing CR was present in the magnocellular part. PV-ir fibers and a moderate number of small cells were observed in the fetal, perinatal as well as the adult parvocellular part. A few PV-ir neurons were seen in the magnocellular part of the fetal and perinatal brains. Our results indicated that: (1) the magnocellular and parvocellular parts of the red nucleus were well-demarcated portions from fetal life onwards, thus a dominance of the parvocellular part over the magnocellular occurred during development; (2) the magnocellular part was more prominent in the fetal period than in adulthood; (3) neurons in the red nucleus were heterogeneous with respect to the immunoreactivities towards the three calcium-binding proteins examined; (4) the transient prominence of the magnocellular part might be a substrate for a specific transitory pattern of motor behaviour.

Brain↗
PubMed1986

[Synaptic responses of neurons of the red nucleus of the alert cat to stimulation of the sensomotor area of the cortex and the nucleus interpositus of the cerebellum].

Postsynaptic potentials of the red nucleus neurons evoked by stimulation of the cortical sensomotor region and the cerebellar nucleus interpositus were studied in chronic experiments on awake cats by means of intracellules revording. Rubro-spinal neurons identified by their antidromic activation in response to the stimulation. A decrease of the critical depolarization level was a specific feature for mono- and polysynaptic responses of the red nucleus neurons in alert animals. Isolated EPSPs, therefore, were rarely recorded as well as a great number of polysynaptic potentials. Burst discharges of rubro-spinal neurons and intensive activity of the red nucleus interneurons, were observed.

Animals↗
PubMed2000

Macaque red nucleus: origins of spinal and olivary projections and terminations of cortical inputs.

The cerebellar, spinal, bulbar, and cortical connections of the mammalian red nucleus imply a motor role. However, what information the red nucleus receives, processes, and distributes is poorly understood, partly because the rubral microcircuitry, especially in primates, remains incompletely defined. Multiple retrogradely transported fluorescent tracers were injected into the spinal cord and inferior olive of the macaque to label rubrospinal and rubroolivary neuron populations, respectively. Anterograde dextran amines were used to label the terminals of corticorubral neurons. These data provided the topographic framework for examining the morphology of rubral neurons in the accompanying paper (Burman et al. [2000]). Soma profiles of rubrospinal and rubro-olivary neurons were respectively segregated in the magnocellular and parvocellular nuclei. A subpopulation of neurons (DL-spinal cells) with their somas immediately dorsolateral to the rostral magnocellular nucleus and its capsule, also projected to the spinal cord, as did clusters of neurons in the periaqueductal grey matter. Terminals of corticorubral axons originating from ipsilateral primary motor area 4 (the densest projection), the supplementary motor area, cingulate area 24, area 8, and posterior parietal area 5, were each mapped in the parvocellular red nucleus. Only area 4 projected to the magnocellular red nucleus, and this projection as small. DL-spinal neurons had no cortical input. The somatotopic organization of rubral connections was examined only in (a) the corticorubral input from motor area 4, and (b) the rubrospinal and DL-spinal projections. These connections and their somatotopic alignment, were mapped in a 3-dimensional reconstruction of the red nucleus.

Animals↗