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At least 19 recordsLinked to original sources

Effects of lidocaine injection in the interpositus nucleus and red nucleus on conditioned behavioral and neuronal responses.

The role of the cerebellum and the red nucleus in the conditioned eyeblink response was assessed, using a combination of reversible lesions and multiple-unit extracellular recording in the awake, behaving rabbit. Lesion, recording, and stimulation experiments have indicated that both of these structures are involved in the performance of learned skeletal muscle responses. The present study sought to distinguish the relative contributions of the interpositus nucleus and the red nucleus to the expression of the learned response by recording behavior-related multiple unit activity in one structure while reversibly inactivating the other via injections of local anesthetic. Results indicate that inactivating either the interpositus or the red nucleus temporarily abolishes the learned eyeblink response. Injection of lidocaine into the interpositus also abolishes the neuronal unit model of the conditioned response in the red nucleus, while injection into the red nucleus does not affect the model in the interpositus. These results are consistent with the hypothesis that the red nucleus acts as a relay for motor commands from the cerebellum, and that the plasticity that generates conditioned responses occurs in the cerebellum or an afferent structure.

Animals↗

Effects of diphenylhydantoin on the spontaneous activity of Purkinje, nucleus interpositus, red nucleus and motor cortex cells.

(1) Extracellular multiunit recordings were made of the spontaneous activity in cerebellar Purkinje cells, nucleus interpositus, red nucleus and sensorimotor cortex in acute cat preparations. (2) Changes in this spontaneous neural activity produced by the administration of diphyenylhydantoin (DPH) were studied. DPH was infused i.v., generally at a concentration of 2.5 mg/ml and at a rate varying from 0.08 to 0.48 mg/kg/min. Two different patterns of infusion were used: fixed time, variable rate and variable time, fixed rate. Pulsed doses were also given at intervals of 5--10 min. (3) DPH at a level of 10--20 mg/kg produces a significative initial deceleration in all structures followed by a significative acceleration in the Purkinje cells, nucleus interpositus and red nucleus as a dose of 20--30 mg/kg is reached. Higher levels caused a profound depression of multiunit activity. (4) The activation produced by DPH is oscillatory (3--5/min) in character and is composed of 'trains' which occur at a rate of 20--30/sec with very rapid discharge frequencies (600--800 Hz). (5) A direct significant correlation was found between DPH serum levels and the intravenously administered dose. The activating DPH dose (20--30 mg/kg) corresponded to serum levels of 24--32 micrograms/ml. (6) The possibility is discussed whether the anticonvulsant action of DPH may be due in part to the production of rhythmic oscillatory activity in the cerebello-rubro-olivo-cerebellar ciruit and the depression of the cerebellothalamic-cortical pathway.

Animals↗

Elicitation, modification, and conditioning of the rabbit nictitating membrane response by electrical stimulation in the spinal trigeminal nucleus, inferior olive, interpositus nucleus, and red nucleus.

Elicitation of responses by electrical brain stimulation (EBS) was related to the synaptic distance of the target nucleus from the accessory abducens. Specifically, responses to EBS in the spinal trigeminal nucleus (TRIG) and red nucleus (RN) increased as a positive function of stimulation parameters. Responding to EBS in the interpositus nucleus (IP) was lower, and responding to EBS in the inferior olive (IO) was negligible. EBS in the TRIG, IP, and RN nuclei was then paired with a tone conditioned stimulus (CS). The CS modified responses for EBS in RN and TRIG but not IP. CS-EBS pairings yielded conditioned response (CR) acquisition, in which Groups TRIG, IP, and RN reached asymptotes of 90%, 70%, and 43% CRs, respectively. Thus, contrary to previous findings, EBS in the efferent pathway can support CR acquisition. The results are discussed with respect to the role of projections from the RN to the cerebellar cortex and the TRIG nucleus.

Abducens Nerve↗

Induction of microglial reaction and expression of nitric oxide synthase I in the nucleus dorsalis and red nucleus following lower thoracic spinal cord hemisection.

In the present study, immunohistochemical stainings for OX-6, OX-42, nitric oxide synthase I and II as well as nitrotyrosine were used to investigate possible correlation among microglial reactivity, nitric oxide synthase upregulation, peroxynitrite involvement and neuronal death in the nucleus dorsalis and red nucleus following lower thoracic spinal cord hemisection. Significant neuronal loss was found in the ipsilateral nucleus dorsalis and contralateral red nucleus after cord hemisection. A distinctive microglial reaction for OX-42 could be observed from one to four weeks post axotomy in the ipsilateral nucleus dorsalis; by contrast, it was observed on both sides of the red nucleus from one to three weeks following cord hemisection. The activated microglial cells showed some degree of hypertrophy. From the microglial immunoreactivity as well as their appearance, it was speculated that microglial activation might be beneficial or protective to the axotomized neurons. In normal and sham-operated rats, neurons of the nucleus dorsalis were not nitric oxide synthase I reactive. Three weeks after cord hemisection, neurons in the ipsilateral nucleus dorsalis below the lesion showed strong immunoreactivity. Neurons in the red nucleus that normally displayed weak nitric oxide synthase I immunoreactivity showed an increase on both sides of the nucleus. These results suggested that nitric oxide synthase I expression in the nucleus dorsalis following axotomy was synthesized de novo and might act as a neurotoxic agent. However, the bilateral increase in expression of nitric oxide synthase I in the red nucleus after lower thoracic cord hemisection was due to up-regulation of the constitutive enzyme and might have some neuroprotective function. Our results also suggested that peroxynitrite played no or little role in the neurodegeneration in the nucleus dorsalis and red nucleus following axotomy.

Animals↗

Distinct roles of oxidative stress and antioxidants in the nucleus dorsalis and red nucleus following spinal cord hemisection.

Oxidative stress plays an important role in the pathogenesis of neurodegeneration after the acute central nervous system injury. We reported previously that increased nitric oxide (NO) production following spinal cord hemisection tends to lead to neurodegeneration in neurons of the nucleus dorsalis (ND) that normally lacks expression of neuronal NO synthase (nNOS) in opposition to those in the red nucleus (RN) that constitutively expresses nNOS. We wondered whether oxidative stress could be a mechanism underlying this NO involved neurodegeneration. In the present study, we examined oxidative damage evaluated by the presence of 4-hydroxynonenal (HNE) and iron accumulation and expression of putative antioxidant enzymes heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) in neurons of the ND and RN after spinal cord hemisection. We found that HNE expression was induced in neurons of the ipsilateral ND from 1 to 14 days following spinal cord hemisection. Concomitantly, iron staining was seen from 7 to 14 days after lesion. HO-1, however, was only transiently induced in ipsilateral ND neurons between 3 and 7 days after lesion. In contrast to the ND neurons, HNE was undetectable and iron level was unaltered in the RN neurons after spinal cord hemisection. HO-1, SOD-Cu/Zn and SOD-Mn were constitutively expressed in RN neurons, and lesion to the spinal cord did not change their expression. These results suggest that oxidative stress is involved in the degeneration of the lesioned ND neurons; whereas constitutive antioxidant enzymes may protect the RN neurons from oxidative damage.

Aldehydes↗

Distinct subcellular localization and mRNA expression of neuronal nitric oxide synthase in the nucleus dorsalis and red nucleus and their correlation with inducible transcription factors after spinal cord hemisection.

We previously reported on the differential expression of neuronal nitric oxide synthase (nNOS) in neurons of the nucleus dorsalis (ND) and red nucleus (RN), as well as differential roles of nitric oxide (NO) in these two distinct groups' neurons characterized with different nNOS phenotypes after lower thoracic spinal cord hemisection. To further understand the enzyme, nNOS expression was studied at the subcellular and mRNA levels by using electron microscopic immunohistochemistry (EM-IHC) and in situ hybridization respectively. Possible transcriptional regulation by c-Jun or CREB in the differential nNOS expression in both ND and RN neurons was also studied. nNOS mRNA was not found in the normal ND neurons, but was shown in the normal RN neurons. After spinal cord hemisection, nNOS mRNA was induced in the ipsilateral ND, while upregulated on both sides of the RN, which preceded protein induction or upregulation. By EM-IHC, nNOS immunoreaction products were predominantly bound to the membrane of the mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus, and nuclear envelope in the RN neurons of normal rats as well as rats subjected to spinal cord hemisection. In contrast, nNOS-immunoreactive deposits in the experimental ND neurons were found to be mainly granular, being dispersed throughout the cytoplasmic matrix. It is speculated that the differential subcellular localizationof nNOS indicates that axotomy may trigger different nNOS transcripts and lead to different nNOS isoform expression in the normally non-nNOS- and normally nNOS-containing neurons. c-Jun was induced in the ipsilateral ND neuronsand upregulated only in the contralateral RN neurons. Activation of CREB by phosphorylation was occasionally detectable in the ND neurons, but not in the RN neurons. Double-labeling data showed a large proportion of c-Jun and nNOS colocalization in neurons of the ipsilateral ND and contralateral RN after spinal cord hemisection. However, dissociation of nNOS expression kinetics with c-Jun was observed in the ipsilateral RN. The results implied that nNOS expression might not be under the direct transcriptional regulation by c-Jun, although it seemed to be closely related to the c-Jun expression.

Animals↗

Lesion of the cerebellar interpositus nucleus or the red nucleus affects classically conditioned neuronal activity in the hippocampus.

1. The cerebellum and the hippocampus have been known to be neural structures involved in classical conditioning of the nictitating membrane response in rabbits. The neuronal activities related to conditioning are observed in both structures. It is uncertain, however, whether these conditioning-related neuronal activities are established in parallel or hierarchically. 2. The present study was conducted to observe the effects of lesions of the cerebellar interpositus nucleus(INT) or the red nucleus(RN) on conditioned hippocampal neuronal activity. 3. Rabbits in the first experiment were trained by standard delay conditioning and then given INT lesion by injecting the kainic acid through a cannula previously implanted. Lesions of INT abolished conditioned neuronal responses in the hippocampal CA1 area, which had been established before lesioning, as well as behavioral conditioned responses(CRs). 4. The second experiment was to examine if conditioning-related activities in the hippocampus would develop after RN was lesioned with INT intact. Rabbits were first given unilateral electrolytic lesions of RN followed by conditioning sessions. Besides a few CRs, they failed to show an increase in hippocampal CA1 activity. When training was switched to the contralateral eye, animals showed robust CRs and hippocampal responses immediately. However, training reswitched to the original eye, behavioral and neuronal responses disappeared again. 5. These results suggest that conditioned neuronal activities in the hippocampus depends on the cerebellum and that conditioning-related inputs from INT via RN may be critical for these conditioned neuronal response in the hippocampus.

Animals↗

Cholinergic innervation of the human striatum, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus.

The anatomical organization of cholinergic markers such as acetylcholinesterase, choline acetyltransferase, and nerve growth factor receptors was investigated in the basal ganglia of the human brain. The distribution of choline acetyltransferase-immunoreactive axons and varicosities and their relationship to regional perikarya showed that the caudate, putamen, nucleus accumbens, olfactory tubercle, globus pallidus, substantia nigra, red nucleus, and subthalamic nucleus of the human brain receive widespread cholinergic innervation. Components of the striatum (i.e., the putamen, caudate, olfactory tubercle, and nucleus accumbens) displayed the highest density of cholinergic varicosities. The next highest density of cholinergic innervation was detected in the red nucleus and subthalamic nucleus. The level of cholinergic innervation was of intermediate density in the globus pallidus and the ventral tegmental area and low in the pars compacta of the substantia nigra. Immunoreactivity for nerve growth factor receptors (NGFr) was confined to the cholinergic neurons of the basal forebrain and their processes. Axonal immunoreactivity for NGFr was therefore used as a marker for cholinergic projections originating from the basal forebrain (Woolf et al., '89: Neuroscience 30:143-152). Although the vast majority of striatal cholinergic innervation was NGFr-negative and, therefore, intrinsic, the striatum also contained NGFr-positive axons, indicating the existence of an additional cholinergic input from the basal forebrain. This basal forebrain cholinergic innervation was more pronounced in the putamen than in the caudate. The distribution of NGFr-positive axons suggested that the basal forebrain may also project to the globus pallidus but probably not to the subthalamic nucleus, substantia nigra, or red nucleus. The great majority of cholinergic innervation to these latter three structures and to parts of the globus pallidus appeared to come from cholinergic neurons outside the basal forebrain, most of which are probably located in the upper brainstem. These observations indicate that cholinergic neurotransmission originating from multiple sources is likely to play an important role in the diverse motor and behavioral affiliations that have been attributed to the human basal ganglia.

Acetylcholinesterase↗

Innervation of the caudate nucleus, thalamus and red nucleus by the remaining sensorimotor cortex in cats with fetal or neonatal unilateral frontal cortex removal.

We studied the projections to the caudate nuclei, thalami and red nuclei from the remaining sensorimotor cortex in adult cats that had sustained a unilateral frontal cortex resection prenatally or neonatally. Four cats had the lesion at age E 50-55 and six animals sustained the ablation at age P 8-14 (seven cats were intact controls). All cats grew to young adulthood and then received injections of tritiated leucine-proline in the remaining sensorimotor cortex. Injection sites and axon terminal fields were reconstructed using autoradiography-processed tissue. In all cats the label filled a similar extent of the right pericruciate cortex. Terminal field densities in the subcortical nuclei were estimated using computer-based video software. Three medial-lateral sectors at five coronal levels were examined in the caudate nucleus. Three nuclear groups were analyzed in the thalamus (intralaminary, ventralis lateralis and ventrobasal complex). For the red nucleus, the four quadrants were examined at four coronal levels. The main goal of the study was to assess possible changes in the cortical innervation of the nuclei ipsilateral to the lesion. Therefore, the mean particle counts per nucleus (and per area or sector of nuclei) and per animal group were used to calculate percentage values for the decussated (crossed, or contralateral to the injection site) as a function of the non-decussated (uncrossed, or ipsilateral to the injection site) innervation. The percentage values for the crossed projections were: (a) for the entire caudate nucleus, 61.3% for the intact. 56.7% for the fetal-lesioned and 42.7% for the neonatal-lesioned cats, with no statistical differences between groups; (b) for the thalamus the proportion of crossed projections was minimal fluctuating between a low 0.06-0.16% for the nucleus ventralis lateralis and a high of 2.01-3.46% for the intralaminary nuclei, with the highest values belonging to the lesioned groups but with no significant differences between groups: (c) for the entire red nucleus, 1.98%, 12.74% (P < 0.05) and 6.76% for the intact, fetal- and neonatal-lesioned cats respectively. In the lesioned cats, the topography of the distribution of the axon terminals was bilaterally the same as in the controls. In conclusion, only the red nucleus of the frontal-lesioned cats showed an increased crossed innervation from the remaining sensorimotor cortex but this was relatively weak and statistically significant only for the fetal-lesioned animals. These results as well as the literature suggest that: (a) the crossed corticorubral projections in fetal cats may represent true reinnervation (i.e., newly originated, no preexisting terminals); (b) the relative paucity of the crossed projections in the present cats as compared to the extensive reorganization of subcortical terminals seen after cerebral hemispherectomy (our original postnatal lesion model) may be due to the much smaller size of the present cortical lesion which presumably induced only a limited amount of subcortical nuclear deafferentation.

Animals↗

Age related changes in neuron number in the mouse red nucleus.

The red nucleus of the ASH/TO stain mouse brain was examined at 6, 22, 25, 28 and 31 months of age using quantitative histological techniques. Three types of neurons, large, medium and small, were identified on grounds of size and structural characteristics. The number of large neurons remained constant from 6 to 25 months of age before declining from 385 +/- 24 at 25 months to 126 +/- 12 at 31 months. The number of medium neurons remained constant from 6 to 31 months of age with an overall mean of 1139. The number of small neurons showed a slight decline at 31 months of age. The nuclear diameter of large neurons increased from 14.7 microns at 25 months to 15.6 microns at 28 months and this increase in diameter was statistically significant. The nuclear diameter of neither medium (mean 12.0 microns) nor small neurons (mean 9.6 microns) varied significantly with age.

Aging↗

Spinal projections of the cat parvicellular red nucleus.

Traditionally, the red nucleus of the cat is divided into two parts: a large-celled, magnocellular, division (RNm) and a small-celled, parvicellular, division (RNp). The RNm projects to the spinal cord and receives input from the cerebellar interpositus nucleus. The RNp projects to the inferior olive and receives input from the cerebellar dentate nucleus. In this report, we reexamine the connections of the red nucleus using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Our findings demonstrate that the cat RNp has a large caudal and lateral region that projects to contralateral spinal cord and not to the inferior olive. The spinally projecting region of RNp receives input from the dentate nucleus and a lateral segment of anterior interpositus. Cervical projections from the red nucleus show a topography with the rostral portion of RNp favoring upper segments and the caudal portion of RNm favoring lower segments. The results show that dentate output can influence spinal activity without passing through the cerebral cortex. For the control of movements such as reaching and grasping, we suggest that RNp and dentate focus on the control of proximal limb musculature, whereas RNm and the anterior interpositus focus on the control of distal limb musculature. We also suggest that other species are likely to have a small-celled area of red nucleus projecting to the spinal cord.

Animals↗

An excitatory input to nucleus raphe magnus from the red nucleus in the cat.

In chloralose-anaesthetized cats, with the cerebellum removed, stimulation in the red nucleus excited the majority (60-65%) of neurones in nucleus raphe magnus (NRM), including raphespinal neurones. Evidence was obtained for both monosynaptic and polysynaptic excitation. The projection was confirmed by recording antidromic responses in the red nucleus to stimulation in NRM. It is suggested that the role of NRM in motor control is to inhibit spinal flexion responses to peripheral stimuli so that commands from the red nucleus and other motor control regions may take place without interruption.

Animals↗

Geometry of rubrospinal, rubroolivary, and local circuit neurons in the macaque red nucleus.

The primate red nucleus consists of three main neuron subpopulations, namely, rubrospinal neurons in the magnocellular nucleus, rubroolivary cells in the parvocellular nucleus, and local circuit neurons in both subnuclei: Each subpopulation has unique cerebellar and neocortical inputs. The structural framework for the interactions of these rubral subpopulations remains poorly defined and was the focus of this study in six macaques. Somata of rubrospinal neurons, dorsolateral-spinal (DL-spinal) neurons, as defined in the accompanying paper (Burman et al. [2000] J. Comp. Neurol., this issue), and rubroolivary neurons were labeled retrogradely first with Fast Blue injected either into the cervical spinal cord or the inferior olive. The soma/dendrite profiles of selected cells (53 rubrospinal, 19 DL-spinal, and 17 rubroolivary cells) were visualized by the intracellular injection of Lucifer Yellow/biocytin in fixed slices (400 microm thick) of midbrain. The descriptive statistics of the somata and the dendritic arborization of each rubral neuron type were established. Projection neuron subpopulations had similar but differentiable soma/dendrite profiles, with four to six slender, spine-bearing dendritic trees radiating out approximately 400 microm from the soma. Twelve presumed interneurons, all in the parvocellular nucleus, differed from projection neurons in that they had smaller somata and many slender, spine-bearing segments that constituted the multibranching dendrite profile that radiated out approximately 250 microm from the soma. A tentative model of the macaque rubral microcircuitry was developed, and its functional implications were explored. It incorporated 1) the known topography of the nucleus and its connections, 2) our data specifying the soma/dendrite morphology of the three main rubral neuron types, and 3) the ultrastructure reported by other laboratories of intrarubral synaptic connections.

Animals↗

Anatomical evidence of a reciprocal connection between the posterior thalamic nucleus and the parvocellular division of the red nucleus in the rat. A combined retrograde and anterograde study.

The functional and anatomical organizations of the magnocellular part of the red nucleus are now well established. Our knowledge of the parvocellular part is, however, more limited. Using both anterograde and retrograde tracing methods, the present study suggests in the rat the existence of a large projection from the posterior thalamic nucleus to the parvocellular part of the red nucleus. In turn, the parvocellular part of the red nucleus sends a weaker projection to the posterior thalamic nucleus. Three different tracers were utilized (horseradish peroxidase alone, horseradish peroxidase conjugated to wheat germ agglutinin and Phaseolus vulgaris leucoagglutinin), all of which gave similar results. The posterior thalamic nucleus is known to receive a large proportion of somatosensory afferents. It is suggested, therefore, that in addition to receiving cerebellar and cortical inputs, the parvocellular part of the red nucleus has access to highly integrated somatosensory and/or nociceptive information delivered by the posterior thalamic nucleus.

Animals↗