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PubMed1988

Pharmacological analysis of the magnocellular red nucleus during classical conditioning of the rabbit nictitating membrane response.

Previous experiments have suggested that the red nucleus is an essential structure in the neural pathways subserving the conditioned responses (CRs) elicited in several simple associative learning paradigms. The present investigation confirms the involvement of the magnocellular red nucleus in production of the classically conditioned nictitating membrane response in the rabbit and suggests that gamma-aminobutyric acid (GABA) processes within this structure are involved in expression of the CR. Specifically, these studies demonstrate that microinfusion of a GABA antagonist (either picrotoxin or bicuculline methiodide) into the magnocellular red nucleus can selectively and reversibly reduce or abolish retention of the CR, without altering the unconditioned reflex response. Furthermore, these pharmacological manipulations that disrupt the CR are both anatomically and pharmacologically specific, and demonstrate a predictable dose-dependent function. These findings suggest that GABAergic processes within the magnocellular red nucleus are part of the critical circuitry subserving the CR.

Animals↗
PubMed1979

Interaction of peripheral and cerebellar inputs to red nucleus neurons.

In chloralose anesthetized cats responses of red nucleus neurons to cerebellar cortical or peripheral stimulation are described. Interactions between cerebellar (conditioning) and peripheral (test) stimulations were studied at various interstimulus intervals. Peripheral stimulation alone typically evoked a complex response consisting of an early (15 ms latency) burst, a period of depression of activity (inhibition, lasting up to 300 ms) and a late, long-lasting (on an average 300 ms) excitation. Cerebellar cortical stimulation resulted in a similar pattern of response; but it was composed predominantly of only two phases, an initial inhibition followed by a prolonged late discharge. With conditioning- testing intervals in a range of 10-150 ms, depending on the cell, there was a conspicuous depression of the sh0i.t-latency test excitation, followed by a prominent potentiation of this component. An occlusion of the inhibitory or late excitatory responses occurred when conditioning-testing stimuli were applied with an interval shorter than 0.5 s. It is suggested that the early excitation and the subsequent late components are generated in the red nucleus by independent mechanisms. The initial depression of the early test response is explained as an effect of Purkinje cell inhibition, and the later potentiation as a result of temporary blockage of the cerebellar cortex to afferent input.

Animals↗
PubMed2002

Distinctive patterns of connectivity between the zona incerta and the red nucleus of rats.

In an effort to understand better the function of the zona incerta of the thalamus, this study has examined the organisation of its connections with the red nucleus of the midbrain. Injections of the tracers biotinylated dextran (BD) or cholera toxin subunit B (CTb) were made into either the zona incerta or red nucleus of Sprague Dawley rats and the resultant labelling was examined. The results indicate that there are strong connections between the zona incerta and red nucleus; further, that these connections make distinct patterns in each nucleus. After incertal injections, labelling is found mainly within the smaller parvocellular lamina of the red nucleus, leaving the larger magnocellular lamina barren of labelling. After rubral injections, labelling is seen across all of the four distinct sectors of the zona incerta, but with a concentration within the medial region of each. Overall, the results indicate that the zona incerta is in a position to influence the motor related functions of the parvocellular lamina of the red nucleus. It is suggested that these results, when taken together with recent reports of a large interpositoincertal pathway, render the zona incerta as a synaptic interface between cerebellar and rubral circuits.

Animals↗
PubMed1993

Reversible lesions of the red nucleus during acquisition and retention of a classically conditioned behavior in rabbits.

Previous lesion, recording, and stimulation studies implicated the cerebellum and its associated brain-stem circuitry as essentially involved in classical conditioning of discrete, somatic muscle responses. This is a companion to our study of interpositus cooling, which showed that the formation of a memory was prevented. In the present study, we assess the red nucleus for its role in the plasticity associated with learning and memory by using local cooling as a reversible lesion technique. A cooling probe was implanted lateral to the red nucleus. Recording electrodes were implanted in the right red nucleus and the left interpositus nucleus. Animals were trained for 5 days with the cooling probe activated. No behavioral conditioned responses (CR) developed, and multiple unit recordings related to learning did not develop in the red nucleus. However, a learning related model did develop in the interpositus. After 5 days of training while cooling, animals were given 5 days of normal training (cooling probe inactive) to assess retention. Substantial savings were evident when normal training was given. CRs appeared quickly on the first day of normal training, and multiple unit models were present in both red nucleus and interpositus nucleus. These results support the idea that the red nucleus is a necessary efferent for the memory trace formed in the cerebellum.

Animals↗
PubMed1983

Preservation of physical dimensions in a model of reactive synaptogenesis in the red nucleus.

Collateral sprouting of cerebral cortical fibers in the red nucleus following destruction of the interpositus nucleus may be effective in restoring activity of rubral neurons. Shrinkage of the deafferented red nucleus was measured to estimate its effect on recording neural activity and its contribution as a stimulus for sprouting. The results suggest that rubral morphology is preserved during the early time course of collateral sprouting when electrophysiological changes are evident.

Animals↗
PubMed1993

The temporary inactivation of the red nucleus affects performance of both conditioned and unconditioned nictitating membrane responses in the rabbit.

These experiments are part of a series of studies examining the role of the red nucleus in the performance of the conditioned and unconditioned nictitating membrane reflexes in the rabbit. Specifically, the experiments test the hypothesis that the temporary inactivation of the red nucleus selectively affects the performance of the conditioned reflex. The experiments were designed to assess the effects of lidocaine and control saline microinjections on conditioned as well as unconditioned responses in both paired and unpaired trials. Rabbits were chronically implanted with cannulae through which small injecting tubes were passed stereotaxically to the red nucleus. The animals were conditioned using a delay paradigm in which a 1 kHz tone and an air puff applied to the cornea were used as the unconditioned and conditioned stimulus, respectively. Once conditioned, the effects of either lidocaine or saline injection were evaluated while alternating paired trials with unpaired trials in which only the air puff was applied. The principal finding of this study was that the amplitudes of both the conditioned and unconditioned responses were reduced following lidocaine injection into the red nucleus. The effect on the unconditioned response amplitude could not be ascribed to any interaction between the conditioned and unconditioned responses, since it also was present in the unpaired trials. The reduction in amplitude of the conditioned and unconditioned responses was shown to be correlated with changes in other characteristics of the same responses. The data suggest that the red nucleus contributes to the performance of both the conditioned and unconditioned nictitating membrane reflexes and consequently is not likely to be involved only in pathways responsible for mediating and/or storing the engram for the conditioned reflex.

Acoustic Stimulation↗
PubMed1990

Comparative characteristic of afferent inputs to the dorsal and ventral regions of the magnocellular part of the cat red nucleus.

The mosaic of topical organization of afferent inputs from some cortical, subcortical, including nucleus caudatus, brainstem and spinal cord structures to the magnocellular part of the cat red nucleus has been revealed by microiontophoretic injection of horseradish peroxidase and subsequent study of retrograde axonal transport of the enzyme. Substantial differences between afferent inputs of dorsal and ventral regions of the red nucleus as representation zones of fore- and hind-limbs in this structure were observed. It was found that while a considerable variety of afferent inputs to the ventral regions of the red nucleus exists, the dorsal region receives information from only a restricted number of structures. The trajectories of retrogradely labelled fibre systems of the red nucleus have also been described.

Afferent Pathways↗
PubMedDate not supplied

A common somaesthetic pathway to red nucleus and motor cortex.

Comparable short latency somaesthetic responses have been observed in the red nucleus and the motor cortex. Since previous experiments showed that a ventral spinal ascending pathway could account for red nucleus responses, the present experiments were designed to establish whether the same pathway could also transmit the short latency peripheral inputs to motor cortex. Two experimental data argue in favour of a such organization: (1) Using the collision technique, it was demonstrated that somaesthetic responses recorded in red nucleus cells are transmitted by collaterals of ascending fibres ending in the ventrobasal thalamus. (2) Intracellular recordings from identified corticospinal cells were performed on cats acutely prepared on section of the brachium conjunctivum and the dorsal columns of the spinal cord. Cortico-cortical connections to motor cortex were also eliminated by lesions of the ipsilateral sensory cortex and contralateral motor cortex. With this preparation it is still possible to record postsynaptic potentials after stimulation of primary afferent fibres in the dorsal columns, caudally to their section. The existence of these somaesthetic parallel inputs to rubro- and corticospinal cells suggest that the ongoing movement might be corrected on-line by these two pathways.

Afferent Pathways↗
PubMedDate not supplied

Expression of a kinase anchoring protein 79 and synaptophysin in the developing human red nucleus.

Our previous study showed that in the human fetal and neonatal brain, the magnocellular and parvocellular parts of the red nucleus can be well delineated by calcium-binding proteins. To study the development of rubral afferents, the expression of A kinase anchoring protein 79 (AKAP79) and synaptophysin (SYN) was examined in the human fetal red nucleus. It was found that during prenatal development both AKAP79 and SYN expression increased gradually although a major alteration in the distribution of the proteins within the two compartments of the red nucleus was not observed. In AKAP79 immunopreparations, the magnocellular part became well demarcated from 23 weeks of gestation onwards and both parts showed punctate immunolabelling with moderate to high packing densities of immunoreactive cells. SYN immunoreactivity with a punctate appearance was, however, mainly located in the parvocellular part. It was evenly distributed throughout the compartment at 14-22 weeks of gestation, and then from 23 weeks to the time of birth, there was a pericellular arrangement of SYN. Our observations are mainly in line with connectivity data regarding the red nucleus.

A Kinase Anchor Proteins↗
PubMed1985

Brachium conjuntivum and rubrobulbar tract: brain stem projections of red nucleus essential for the conditioned nictitating membrane response.

The trajectory of the rubrobulbar tract in rabbit to the level of the accessory abducens nucleus is described: orthograde labeling of fibers of the rubrobulbar tract following horseradish peroxidase implants into red nucleus of 8 animals permitted ad hoc analysis of the effects of brain stem lesions on the rabbit's conditioned nictitating membrane response. Twenty-four rabbits, trained to give conditioned NM responses from both eyes, received unilateral lesions of the right pontine brain stem. Six of the 7 cases of post-lesion disruption of ipsilateral conditioned responding involved either ipsilateral brachium conjunctivum or the rubrobulbar tract. This finding, together with a reexamination of data from two related studies from this laboratory strongly support the conclusion that an essential premotor component of the conditioned NM response is a doubly decussating circuit from the interpositus nucleus of the cerebellum to magnocellular red nucleus, via brachium conjunctivum and its decussation, and from red nucleus caudally, via the ventral tegmental bundle and the rubrobulbar tract, to the accessory abducens nucleus, where motoneurons involved in the NM response are located. These findings are consistent with published reports on the essential role of interpositus nucleus of the cerebellum in NM conditioning. The possible role of the supratrigeminal reticular formation in this learned behavior is also discussed.

Abducens Nerve↗
PubMed2003

Glial fibrillary acidic protein expression in the hamster red nucleus: effects of axotomy and testosterone treatment.

Testosterone propionate (TP) administration coincident with facial nerve axotomy in the hamster attenuates glial fibrillary acidic protein (GFAP) expression in the facial nucleus that is normally increased following axotomy alone. This ability of TP to modulate astrocyte activity has been linked to the ability of steroid hormones to enhance the regenerative response of injured motor neurons. In an ongoing study designed to examine the potential influences of steroid hormones on centrally projecting motoneurons, the astrocyte reaction in the red nucleus was examined. In the present study, in situ hybridization was used to assess changes in GFAP mRNA in the hamster red nucleus following spinal cord injury (SCI) and TP treatment. Castrated male hamsters were subjected to right rubrospinal tract (RST) transection at spinal cord level T1, with half the animals implanted subcutaneously with Silastic capsules containing 100% crystalline TP and the remainder sham implanted. The uninjured red nucleus served as an internal control. Postoperative survival times were 1, 2, 7, and 14 days. Qualitative-quantitative analyses of emulsion autoradiograms were accomplished. Axotomy alone resulted in a significant but transient increase in GFAP mRNA levels at 2 days postoperative in the injured red nucleus compared with the contralateral uninjured red nucleus. However, in TP-treated animals, GFAP mRNA levels were no different than control levels at 2 dpo but were significantly increased at 7 dpo relative to contralateral control. Additionally, the increase in GFAP mRNA levels following TP treatment was significantly smaller than following axotomy alone. These data suggest that testosterone both delays and reduces the astrocytic reaction in the red nucleus following rubrospinal tract axotomy, and confirms a difference between peripheral and central glial responses to axotomy and steroid administration.

Androgens↗
PubMed1983

Cerebellar cortical afferents from the red nucleus in the cat.

A crossed projection from the red nucleus to the cerebellar cortex in the cat has been demonstrated by means of retrograde transport of the wheat germ agglutinin-horseradish peroxidase complex. The majority of projecting neurons are situated in the rostral part of the red nucleus and have a maximum diameter of more than 20 microns. The findings indicate that rubrocerebellar fibers terminate in intermediate parts of the anterior and posterior cerebellar cortical lobes.

Afferent Pathways↗
PubMed1989

Changes in red nucleus neuronal development following maternal alcohol exposure.

The red nucleus of Swiss Webster mouse fetuses was examined for morphological changes following maternal ethanol exposure. Pregnant females were given a liquid diet containing 30% or 0% ethanol-derived calories. Changes in numerical density of neurons and in neuronal nuclear volume were found in the rostral red (RR) nucleus of ethanol-exposed pups but not in the caudal red (CR) nucleus. Because of the integrative nature of the RR, changes in neuronal morphology that might relate to synaptic connections could affect the behavioral response mechanisms of these offspring.

Animals↗
PubMed1980

The red nucleus of the monkey. Topographic localization of somatosensory input and motor output.

The topographic organization of somatosensory input to the primate red nucleus was investigated by studying receptive fields of rubral neurons, and that of the motor output by delivering trains of microstimulating pulses to evoke movements. A receptive field was identified in 191 of 208 rubral neurons. Most neurons (172) responded to passive movement of one or two joints including digits but some (26) had a cutaneous input. Neurons in both the parvocellular (RNpc) and magnocellular (RNmc) divisions of the nucleus had receptive fields. Neurons which responded to stimulation of the forelimb were located in the dorsomedial part of the nucleus. Those responsive to stimulation of the hindlimb were in the ventrolateral part. Thin regions on the dorsal and ventrolateral borders of the nuclei, respectively, contained neurons responsive to face and tail stimulation. Within the regions representing each limb, neurons receiving an input from the extremity (hand or foot) formed a core surrounded by neurons with an input from more proximal segments. This core extended uninterrupted throughout the RNpc and RNmc. Movements of individual limb segments including digits were readily evoked by microstimulating in the RNmc with thresholds as low as 3 microA. In most cases, movements were evoked in the direction opposite to the passive movement which drove the neurons at the stimulating site, although fibers of passage limited the analysis of the sensory input-motor output organization with stimulation. We conclude that there is topographic localization of somatosensory input and motor output in the macaque red nucleus. Furthermore, the red nucleus of monkeys contributes to the control of independent movements of limb segments including digits, although the number of axons it sends to the spinal cord is less than 1% of the number of corticospinal axons.

Animals↗
PubMed1994

The postnatal development of the GABAA/benzodiazepine receptor in the rat red nucleus.

The development of the GABAA/Benzodiazepine receptor (GABAAR) in the red nucleus was studied using 3H-flunitrazepam (FNZ) as the probe. Saturation binding assay showed that the Bmax of the ligand to the membranes of the nucleus increased from 0.50 +/- 0.04 nmol/mg protein at postnatal day 4, to 0.71 +/- 0.1 and 0.78 +/- 0.08 at day 7 and day 10. At day 20 the Bmax decreased to a level near day 4 and persisted until day 40. However, the affinity of 3H-FNZ to the receptor remained quite constant. At least 4 proteins of 51kD, 53kD, 59kD and 62kD in the nucleus were labeled by 3H-FNZ, as revealed from photoaffinity binding and SDS-PAGE. The labeling of 53kD, 59kD and 62kD was high at earlier ages than day 10, whereas the 51kD was predominent from day 10 to day 40. Receptor binding autoradiography of the nucleus also showed that the most dense labeling was seen around day 10. The early transient increase in the GABAAR of the red nucleus may indicate the plasticity of the nucleus in response to environmental changes after birth.

Age Factors↗
PubMed1992

Susceptibility to seizures produced by chemical convulsants and maximal electric shock in rats after electrolytic lesions into the red nucleus.

Bilateral electrolytic lesions into the red nucleus (RN) of rat elicit an increase in susceptibility to seizures induced by pilocarpine, kainic acid, isoniazid, pentylenetetrazole, bicuculline and maximal electric shock (MES). It was also observed that carbachol-induced wet-dog shakes were increased in the RN-lesioned rats. The brain acetylcholine (ACh) and gamma-aminobutyric acid (GABA) concentrations were significantly decreased in the striatum and substantia nigra, respectively. There were no changes in electroencephalogram (EEG) recordings in the RN-lesioned group compared with sham-operated rats. Based on the results it is proposed that the RN is involved in the generalization and acceleration of seizure activity through the cholinergic and GABA-ergic system.

Acetylcholine↗
PubMed1987

Electrophysiological peculiarities of cortical inputs to the cat red nucleus.

Complex multicomponent EPSPs of the red nucleus rubro-spinal neurons evoked by stimulation of the sensorimotor cortex and associative fields of the parietal cortex were studied in acute pentobarbitalized cats by intracellular recording technique. Complex cortical EPSPs were recorded in 2/3 of the neurons studied. Components of the EPSPs in question were distinguished by using stimulation of various frequency and intensity. The first component of the EPSPs appearing at the lowest threshold was found to have a short and stable latency, stable rising time for depolarization and was able to follow high frequencies of stimulation. The second component was more variable, although in some EPSPs it too had a short latency, was stable enough and, like the first component could be classified as monosynaptic. The complex character of the EPSPs recorded persisted after the removal of the cerebral gray and was observed when stimulating the white matter so excluding its cortical origin. The first two components of the EPSP were evoked by corticofugal impulsation propagating at an average velocity of 18.5 m/s and 7.5 m/s being supposedly the result of activation of the slow-conducting pyramidal and cortico-rubral neurons. In some rubro-spinal neurons they were characterized by a fast rising phase being apparently an electrophysiological manifestation of the activation of axosomatic synapses.

Afferent Pathways↗
PubMed1982

Autoradiographic study of the neurogenesis of the inferior olive, red nucleus and cerebellar nuclei of the rat brain.

This study provides basic data on the time of origin as well as on the spatio-temporal setting pattern of the neurons of the red nucleus, the inferior olivary complex and the cerebellar nuclei during ontogenesis of the rat brain. The first neurons of the olive form on day 12. In the adult they set in the rostral part of the dorsal accessory olive and in the minor subgroups associated with the medial accessory olive. On day 13, neurogenesis is intense in both divisions of the red nucleus, in all areas of the inferior olivary complex, in the medial and interpositus cerebellar nuclei and in the small-celled part of the lateral cerebellar nucleus. On day 14, neurogenesis is completed in the magnocellular division of the red nucleus and in the dorsal accessory olive but the neurons of the principal and medial accessory olives, of the rostral and caudal poles of the medial cerebellar nuclei, of the interpositus and lateral cerebellar nuclei as well as those of the parvocellular division of the red nucleus are still formed. Our study suggests that in the rat brain the neurons of the nuclei involved in the rubro (parvo)-olivo-cerebello-rubral and rubro (magno)-reticulo-cerebello-rubral loops develop on days 13 and 14 of gestation. Maturation, cytoarchitecture and phylogeny are also discussed.

Animals↗