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A quantitative electron microscope study of cerebellar axon terminals on the magnocellular red nucleus neurons in the cat.

In the red nucleus (RN) of the cat, the bouton covering ratio (BCR: the ratio of whole somatic surface length and that covered with axon terminals) and the density of axon terminals in contact with somatic profiles (DAST: the number of axosomatic terminals per micron of somatic surface membrane) were calculated in each neuronal somatic profile over 60 micron in diameter. The mean BCR was 61.4 +/- 1.43 (S.E. M.)%. The mean DAST of axosomatic terminals filled with spherical synaptic vesicles (S-terminals) was 27.7 +/- 0.95, and that of terminals with pleomorphic and/or flattened vesicles (F-terminals) was 10.3 +/- 1.12. Subsequently, sequential changes of the BCR and DAST of intact terminals were examined in the RN deafferented from the cerebellorubral fibers. The mean BCR and DAST were decreased most markedly during the survival period of 4-7 days; thus decrease was chiefly due to degeneration of S-terminals (BCR: 16.7 +/- 1.17 %, DAST of S-terminals: 7.1 +/- 1.12, DAST of F-terminals: 5.8 +/- 1.22). In the RN 11-63 days after the operation, both the BCR and DAST tended to re-increase slightly and the majority of the re-increased terminals appeared to be F-terminals. Possible meanings of this re-increase of axosomatic terminals are discussed.

Afferent Pathways↗

[Synaptic processes in red nucleus neurons in response to stimulation of the entopeduncular nucleus and the globus pallidus of the cat].

Peculiarities of synaptic processes in red nucleus neurons evoked by stimulation of nucleus entopeduncularis and globus pallidus were studied in acute experiments on cats by means of intracellular recording technique. Stimulation of the structures mentioned was found to evoke mono- and polysynaptic excitation of the rubrospinal neurons. Analysis of time parameters of the recorded excitatory postsynaptic potentials suggested activation of axo-somatic and axo-dendritic synapses. Mechanisms of basal ganglia participation in integration of the red nucleus activity are discussed.

Animals↗

Brachium conjunctivum-red nucleus synaptic system in the baboon.

Electrophysiological properties of the brachium conjunctivum-red nucleus (BC-RN) synaptic system were studied in barbiturate-anesthetized baboon (Papio). Topographic recordings from the mesencephalon demonstrated that most of the BC-evoked activity was restricted to an area histologically identified as red nucleus; however, some brachium-evoked activity was recorded from the surrounding mesencephalic reticular formation. Short latency BC-evoked activity was also recorded from the pons in the region of nucleus reticularis tegmenti pontis. The majority of the BC fibers were found to conduct at a rate of 44 m/sec; a second group of BC fibers with a slower conduction velocity of 23 m/sec was also observed. Brachium-evoked responses recorded from magnocellular and pravicellular RN neurons were short latency responses consistent with monosynaptic activation of these RN neurons by the BC fibers. The BC-RN synaptic system was found to be a very secure synaptic system and could transmit activity at high rates of stimulation with little or no failure. The responsiveness of the BC fibers was found to be similar to that of optic nerve fibers and pyramidal tract fibers, both of which have been characterized as being similar to peripheral A fibers. The responsiveness of the BC-RN synaptic system began to decrease 5 msec after a single or repetitive transmission and was reduced to about 50% of normal responsiveness at 34 msec. This period of reduced postsynaptic responsiveness was associated with a reduction in presynaptic input to RN and suggest that a disfacilitation at the level of the deep cerebellar nuclei may be in part responsible for the subnormal responsiveness of the BC-RN synaptic system.

Animals↗

NMDA receptor blockade rescues Clarke's and red nucleus neurons after spinal hemisection.

Hemisection of the adult rat spinal cord at T9 transects the ascending ipsilateral axons of Clarke's nucleus (CN) neurons and the descending contralateral axons of red nucleus (RN) neurons. Eight weeks following axotomy, 30% of CN neurons and 22% of RN neurons die. Since both nuclei receive glutamatergic input, we wished to examine the possibility that glutamatergic excitotoxicity contributes to axotomy-induced neuronal death in these nuclei. To test this we studied the effects of administration of the NMDA receptor antagonist MK-801 on cell survival after axotomy. When 1 mg/kg body weight MK-801 is administered subcutaneously every day for 1-8 weeks to hemisected rats, cell death is prevented. Treatment with 0.5 mg/kg body weight MK-801 over the same time periods results in only partial rescue of axotomized neurons. Paradoxically, when 1 mg/kg MK-801 administration is restricted to the first week of an 8 week survival period, cell death in both the RN and CN is greatly exaggerated over the cell loss found in saline-treated animals. Withdrawal of 1 mg/kg MK-801 after 1 week of administration induces the loss of 92% of CN neurons, which is 63% greater than that occurring after axotomy alone. If, however, 1 mg/kg MK-801 is withdrawn after 2 weeks post-axotomy in the RN and 3 weeks postaxotomy in CN, all axotomized neurons survive. This rescue is found at 6 months postsurgery, the longest survival period studied, and therefore appears to be permanent. These results suggest that glutamatergic afferent input contributes significantly to the death of axotomized red nucleus and Clarke's nucleus neurons via NMDA receptors located on these neurons.

Animals↗

GABAergic intrinsic interneurons in the red nucleus of the cat demonstrated with combined immunocytochemistry and anterograde degeneration methods.

The presence of glutamic acid decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid (GABA), was investigated in the red nucleus by an immunocytochemical method. The ipsilateral sensorimotor cortex was ablated prior to the immunocytochemical procedures to examine whether cortical neurons make synaptic contacts with GAD-immunoreactive neurons. Small GAD-immunoreactive neurons with a major diameter of 16.1 +/- 3.2 micron (mean +/- S.D.) were observed in the red nucleus under both light and electron microscopy. They were uniformly distributed throughout the nucleus. Degenerating axon terminals were found making synaptic contact with GAD-immunoreactive neurons in the red nucleus, which suggests that there is an input from the ipsilateral sensorimotor cortex to these neurons. This observation, along with our previous findings that GABAergic axon terminals make synaptic contact with the rubrospinal neurons, provides anatomical evidence for the presence of intrinsic GABAergic interneurons which mediate cortical inhibition in cat rubrospinal neurons.

Animals↗

[Activity of neurons of the red nucleus after destruction of the inferior olive in the rat].

The spontaneous frequency of discharge of the red nucleus neurones has been evaluated in the rat before and after total and bilateral destruction of the inferior olive by 3-acetylpyridine. The suppression of the inferior olive increasing the cerebellar inhibition, produces, as a consequence, a consequence, a disfacilitation of the activity of the red nucleus neurones. The process persists for a few days, then a progressive compensation takes place. A month later the average frequency of discharge is recovered but a normal unit activity and motor behaviour are not restaured.

Animals↗

[Neuronal organization of the large-cell segment of the cat's red nucleus].

When studying the neuronal organization of the large-cell part of the red nucleus in cats by the Golgi and Golgi-Kopsch methods three types of neurons have been revealed: large (50-90 mu), medium-sized (20-50 mu) and small cells (8-20 mu). long axon and short-axon neurons were found as well as long-dendrite cells with few thorns (the length of the dendrites form 600-900 mu) and short-dendrite cells (up to 400 mu). On basis ofanalysis of neuronal groups found in the large-cell part of the red nucleus of the cat a neuronal map of this part of the central nervous sytem is composed.

Animals↗

Reciprocal connections between the red nucleus and the trigeminal nuclei: a retrograde and anterograde tracing study.

An anterograde biocytin and a retrograde WGA-colloidal gold study in the rat can provide information about reciprocal communication pathways between the red nucleus and the trigeminal sensory complex. No terminals were found within the trigeminal motor nucleus, in contrast with the facial motor nucleus. A dense terminal field was observed in the parvicellular reticular formation ventrally to the trigeminal motor nucleus. The parvicellular area may be important for the control of jaw movements by rubrotrigeminal inputs. On the other hand, the contralateral rostral parvicellular part of the red nucleus receives terminals from the same zone in the rostral part of the trigeminal sensory complex, where retrogradely labelled neurones were found after tracer injections into the red nucleus. Such relationships could be part of a control loop for somatosensory information from the orofacial area.

Animals↗

Discharge of red nucleus neurons during voluntary muscle contraction: activity patterns and correlations with isometric force.

Discharges of red nucleus neurons were analyzed in the cat during voluntary muscle contractions performed under isometric and anisometric conditions. The observations established: (1) that neurons of the red nucleus modulate their firing in advance of the motor output under both conditions; (2) that increased activity of these neurons is specific to the direction of the force exerted ; (3) that this increase is primarily related to the magnitude of the rate of force change generated by the animal.

Action Potentials↗

An ultrastructural investigation of afferent connections of the red nucleus in the rat.

The pattern and mode of termination of afferents to the red nucleus of the rat were investigated with the electron microscope. Lesions were placed by electrocautery in the sensorimotor cortex or were placed electrolytically in the deep cerebellar nuclei and brachium conjunctivum using a stereotaxic approach. With both types of lesion, degenerating fibres of passage, preterminal axons, and synaptic terminals were observed in greatest numbers on the third post-operative day. Following cerebellar lesions, degenerating terminals occurred on the cell bodies and proximal dendrites of large, multipolar neurons in the magnocellular portion of the red nucleus, and on intermediate and small dendrites in the parvocellular portion. It is concluded that the former are interpositus terminals while the latter are dentate (lateralis) terminals ending on rubrospinal and rubrobulbar neurons respectively. Following lesions of the sensorimotor cortex, small degenerating terminals were observed on the distal dendrites and dendritic spines of parvocellular, rubrobulbar neurons. Large terminals containing round vesicles did not undergo degeneration following either type of lesion. These findings suggest the existence of an interpositorubro-spinal pathway in which the interpositus terminals exert a strong influence on the large, caudally placed rubrospinal neurons. The background excitability of the rostrally located rubrobulbar neurons is probably regulated by the distal cortical input while the more proximally located dentate terminals probably exert a stronger discrete influence over their activity.

Afferent Pathways↗

Plasticity in the distribution of the red nucleus output to forearm muscles after unilateral lesions of the pyramidal tract.

It has been hypothesized that the magnocellular red nucleus (RNm) contributes to compensation for motor impairments associated with lesions of the pyramidal tract. To test this hypothesis, we used stimulus triggered averaging (StTA) of electromyographic (EMG) activity to characterize changes in motor output from the red nucleus after lesions of the pyramidal tract. Three monkeys were trained to perform a reach and prehension task. EMG activity was recorded from 11 forearm muscles including one elbow, five wrist, and five digit muscles. Microstimulation (20 microA at 20 Hz) was delivered throughout the movement task to compute StTAs. Two monkeys served as controls. In a third monkey, 65% of the left pyramidal tract had been destroyed by an electrolytic lesion method five years before recording. The results demonstrate a clear pattern of postlesion reorganization in red nucleus-mediated output effects on forearm muscles. The normally prominent extensor preference in excitatory output from the RNm (92% in extensors) was greatly diminished in the lesioned monkey (59%). Similarly, suppression effects, which are normally much more prominent in flexor than in extensor muscles (90% in flexors), were also more evenly distributed after recovery from pyramidal tract lesions. Because of the limited excitatory output from the RNm to flexor muscles that normally exists, loss of corticospinal output would leave control of flexors particularly weak. The changes in RNm organization reported in this study would help restore function to flexor muscles. These results support the hypothesis that the RNm is capable of reorganization that contributes to the recovery of forelimb motor function after pyramidal tract lesions.

Action Potentials↗

Axotomy-induced alterations in the red nucleus revealed by monoclonal antibody, Py, following a low thoracic spinal cord lesion in the adult rat.

The monoclonal antibody Py was previously developed as a tool for the identification of subpopulations of hippocampal neurons. Here, the differential distribution of Py immunoreactivity in the mid-brain is described showing that Py also serves as a useful marker for other populations of neurons. Medium to strong immunoreactivity was observed in the cell body and dendrites of neurons of the oculomotor nucleus, superior colliculus and substantia gelatinosa reticulata. However, particularly intense Py-immunoreactivity was identified in the magnocellular neurons in the caudal pole of the red nucleus. Unilateral transection of the rubrospinal tract at Th9-10 induced a marked reduction of Py immunoreactivity in the ventrolateral territory of the caudal pole of the axotomised red nucleus. A small but statistically significant reduction of Py-immunoreactivity was first seen at 7 days after surgery and a maximal loss of immunoreactivity (reduced to 66% of control levels) was observed by 21 days after surgery. Immunoreactivity in the axotomised red nucleus was reduced for the duration of the experiment but at the longer survival times studied (3 and 6 months) a small degrees of recovery of staining was observed in small-medium diameter atrophic neurons. These results indicate that monoclonal antibody Py, may be a useful novel and sensitive tool for investigating the cell body reaction of particular populations of axotomised CNS neurons following spinal cord injury.

Animals↗

Somatotopical projections from the supplementary motor area to the red nucleus in the macaque monkey.

Direct projections from the supplementary motor area (SMA) to the red nucleus were investigated in the Japanese monkey (Macaca fuscata). The anterograde tracer, horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), was injected into various regions of the SMA after intracortical microstimulation mapping. After WGA-HRP injection into the orofacial, forelimb, or hindlimb region of the SMA, anterogradely labeled axon terminals were found, respectively, in the medial, intermediate, or lateral portion of the parvocellular part of the red nucleus, bilaterally with an ipsilateral predominance. The results indicate the clear somatotopical arrangement of corticorubral projections from the SMA.

Animals↗

Paw and limb use in skilled and spontaneous reaching after pyramidal tract, red nucleus and combined lesions in the rat: behavioral and anatomical dissociations.

The pyramidal tract and red nucleus send prominent projections to the spinal cord and are thought to co-operate in producing skilled movements. In the present study, skilled reaching for food located on a shelf and spontaneous grasping, handling and eating pieces of pasta were video-recorded and analyzed in control rats, rats with unilateral ibotenic acid lesions of the red nucleus (RN), unilateral pyramidal tract lesions (PT) and combined lesions. The behavioral results suggest that skilled movements are organized as action patterns, easily recognizable and distinctive for each task. In both skilled and spontaneous reaching, PT lesions reduced success more than RN lesions, suggesting a greater role for the PT in guiding limb movements. Both lesions impaired rotatory movements including limb aiming, pronation and supination. RN lesions additionally abolished the arpeggio movement by which the paw is oriented for searching and grasping. Combined lesions were additive as rats lost both rotatory movements and arpeggio. Nevertheless, even after combined lesions, the rats were able to advance the limb, grasp food and withdraw the limb. The sparing following combined lesions suggests that other neural systems as well as compensatory adjustments assist the impaired limb. The results are discussed in relation to the possible distinctive contributions of the rubrospinal and corticospinal tract to the action patterns that comprise skilled movements in rats.

Animals↗

Organization of the mammalian red nucleus and its interconnections with the cerebellum.

The red nucleus in monkeys and rats consists of a magnocellular, rubrospinal portion which receives its cerebellar information from the nucleus interpositus, and a parvocellular, rubroolivary portion which receives cerebellar afferents from the nucleus lateralis. Distinct interpositorubrospinal and dentatorubroolivary projections are therefore common to these 2 species.

Animals↗