Stimulation Of Red Nucleus Research Articles

Role of the lateral reticular nucleus in suppressing the jaw-opening reflex following stimulation of the red nucleus

We found in a previous study that stimulation of the red nucleus (RN) facilitated the low-threshold afferent-evoked jaw-opening reflex (JOR) and suppressed the high-threshold afferent-evoked JOR. It has been reported that the RN projections to the contralateral lateral reticular nucleus (LRt), and stimulation of the LRt inhibits the nociceptive JOR. These facts suggest that RN-induced modulation of the JOR is mediated via the LRt. We investigated whether electrically induced lesions of the LRt, or microinjection of muscimol into the LRt, affects RN-induced modulation of the JOR. The JOR was evoked by electrical stimulation of the inferior alveolar nerve (IAN), and was recorded as the electromyographic response of the anterior belly of the digastric muscle. The stimulus intensity was either 1.2 (low-threshold) or 4.0 (high-threshold) times the threshold. Electrically induced lesion of the LRt and microinjection of muscimol into the LRt reduced the RN-induced suppression of the high-threshold afferent-evoked JOR, but did not affect the RN-induced facilitation of the low-threshold afferent-evoked JOR. These results suggest that the RN-induced suppression of the high-threshold afferent-evoked JOR is mediated by a relay in the contralateral LRt.

Modulation of two types of jaw-opening reflex by stimulation of the red nucleus

The red nucleus (RN) is divided cytoarchitecturally into two parts, the parvicellular part (RPC) and the magnocellular part (RMC). The present study aims, first, to compare the effects of RN stimulation between low- and high-threshold afferents-evoked jaw opening reflexes (JORs), and secondly to compare the size of these effects in the RPC and RMC. Experiments were performed on rats anesthetized with urethane-chloralose. The JOR was evoked by electrical stimulation of the inferior alveolar nerve and was recorded as the electromyographic response of the anterior belly of the digastric muscle. The stimulus intensity was either 1.2 (low-threshold) or 4.0 (high-threshold) times that necessary to elicit the JOR. Conditioning electrical stimulation of the RN significantly facilitated the JOR evoked by the low-threshold afferents. On the other hand, conditioning electrical stimulation of the RN significantly suppressed the JOR evoked by the high-threshold afferents. Microinjection of monosodium glutamate into the RN also facilitated the JOR evoked by the low-threshold afferents, but suppressed that evoked by high-threshold afferents. Facilitation did not differ between the RMC and the RPC. Suppression by the RMC stimulation was significantly greater than that by the RPC stimulation. These results suggest that the RN has distinct functional roles in the control of the JOR.

Stimulation within the cuneate nucleus suppresses synaptic activation of climbing fibers

Several lines of research have shown that the excitability of the inferior olive is suppressed during different phases of movement. A number of different structures like the cerebral cortex, the red nucleus, and the cerebellum have been suggested as candidate structures for mediating this gating. The inhibition of the responses of the inferior olivary neurons from the red nucleus has been studied extensively and anatomical studies have found specific areas within the cuneate nucleus to be target areas for projections from the magnocellular red nucleus. In addition, GABA-ergic cells projecting from the cuneate nucleus to the inferior olive have been found. We therefore tested if direct stimulation of the cuneate nucleus had inhibitory effects on a climbing fiber field response, evoked by electrical stimulation of the pyramidal tract, recorded on the surface of the cerebellum. When the pyramidal tract stimulation was preceded by weak electrical stimulation (5–20 μA) within the cuneate nucleus, the amplitude of the climbing fiber field potential was strongly suppressed (approx. 90% reduction). The time course of this suppression was similar to that found after red nucleus stimulation, with a peak suppression occurring at 70 ms after the cuneate stimulation. Application of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, disodium salt) on the cuneate nucleus blocked the suppression almost completely. We conclude that a relay through the cuneate nucleus is a possible pathway for movement-related suppression of climbing fiber excitability.

Role of the parvicellular reticular formation in facilitating the jaw-opening reflex in rats by stimulation of the red nucleus

In a previous study, we have shown that electrical and chemical stimulation of the red nucleus (RN) facilitates the jaw-opening reflex (JOR). The RN sends projection fibers bilaterally, with contralateral dominance, to the part of the parvicellular reticular formation (RFp) containing premotor neurons projecting to the trigeminal motor nucleus. This implies that RN-induced facilitation of the JOR might be mediated via last-order neurons in the RFp. Here, we address this issue by investigating whether microinjection of lidocaine or l-glutamate into the RFp affects RN-induced modulation of the JOR. Experiments were performed on rats anesthetized with urethane–chloralose. The JOR was evoked by electrical stimulation of the inferior alveolar (IA) nerve and was recorded as an electromyographic response from the anterior belly of the digastric muscle. Conditioning stimulation was delivered unilaterally to the RN 12 ms before the IA test stimulation. We found that local injections of 2% lidocaine (0.5 μl) into the RFp, contralateral to the RN, significantly ( P < 0.05) reduce RN-induced facilitation of the JOR, whereas corresponding injections of 0.1 mM l-glutamate (0.5 μl) significantly ( P < 0.05) increase it. These results suggest that the facilitatory effect of RN stimulation on the JOR is mediated partly by a relay in the RFp.

Functional specialization within the cat red nucleus.

Magnocellular (RNm) and parvicellular (RNp) divisions of the cat red nucleus (RN) project to the cervical spinal cord. RNp projects more heavily to upper cervical levels and RNm projects more heavily to lower levels. The cells in RN are active during reaching and grasping, and the differences in termination suggest that the divisions influence different musculature during this behavior. However, the spinal termination may not reflect function because most rubrospinal terminations are to interneuronal regions, which can influence motor neurons at other spinal levels. To test for functional differences between RNm and RNp, we selectively stimulated RNm and RNp as well as the efferent fibers from each region. Electromyographic activity was recorded from seven muscles of the cat forelimb during reaching. The activity from each muscle was averaged over several thousand stimuli to detect influences of stimulation on muscle activity. Stimulation within the RN produced a characteristic pattern of poststimulus effects. The digit dorsiflexor, extensor digitorum communis (edc), was most likely to show facilitation, and several other muscles showed suppression. The pattern of activation did not differ between RNm and RNp. In contrast, stimulation of RNp fibers favored facilitation of shoulder muscles (spinodeltoideus and supraspinatus), and stimulation of RNm fibers favored facilitation of digit and wrist muscles (edc, palmaris longus, and extensor carpi ulnaris). Fiber stimulation produced few instances of poststimulus suppression. The results from fiber stimulation indicate that the physiological actions of RNm and RNp match their levels of spinal termination. The complex pattern of facilitation and suppression seen with RN stimulation may reflect synaptic actions within the nucleus.

Red nucleus stimulation inhibits within the inferior olive.

Red nucleus stimulation inhibits within the inferior olive. J. Neurophysiol. 80: 3127-3136, 1998. In the anesthetized cat, electrical stimulation of the magnocellular red nucleus (RNm) inhibits responses of rostral dorsal accessory olive (rDAO) neurons to cutaneous stimulation. We tested the hypothesis that RNm-mediated inhibition occurs within the inferior olive by using stimulation of the ventral funiculus (VF) of the spinal cord in place of cutaneous stimulation of the hindlimb. Fibers in the VF terminate on hindlimb rDAO neurons, so inhibition of this input would have to occur within the olive. rDAO responses elicited by VF stimulation were inhibited by prior stimulation of the RNm, indicating that inhibition occurs within the olive. In contrast, evoked potentials recorded from the VF or dorsal columns following hindlimb stimulation were not affected by prior stimulation of RNm, indicating that stimulation of the RNm does not inhibit olivary afferents at spinal levels. RNm stimulation that inhibited rDAO responses had little effect on evoked somatosensory responses in thalamus, indicating that inhibition generated by activity in RNm may be specific to rDAO. To test limb specificity of RNm-mediated inhibition, conditioning stimulation was applied to the dorsolateral funiculus at thoracic levels, which selectively activates RNm neurons projecting to the lumbar cord. Stimulation at thoracic levels inhibited evoked responses from hindlimb but not forelimb regions of rDAO, suggesting that inhibitory effects of RNm activity are limb specific. Several studies have reported that olivary neurons have reduced sensitivity to peripheral stimulation during movement; it is likely that RNm-mediated inhibition occurring within the olive contributes to this reduction of sensitivity. Inhibition of rDAO responses by descending motor pathways appears to be a salient feature of olivary function.

Distribution of rubrospinal synaptic input to cat triceps surae motoneurons.

1. We evoked steady-state synaptic potentials in triceps surae motoneurons of the cat by stimulating the hindlimb projection area of the contralateral magnocellular red nucleus at 200 Hz. We measured the effective synaptic currents (IN) underlying the synaptic potentials using a modified voltage-clamp technique. We also determined the effect of the rubrospinal input on the discharge rate of some of the motoneurons by inducing repetitive discharge with long injected current pulses during which the red nucleus stimulation was repeated. 2. At motoneuron resting potential, the distribution of IN from the red nucleus within the triceps surae pools was qualitatively similar to the distribution of synaptic potentials: 86% of the putative type F motoneurons received a net depolarizing IN from the red nucleus stimulation, whereas only 38% of the putative type S units did so. The mean values of IN were significantly different in the two groups [+4.1 +/- 5.0 nA (SD) for putative type F and -1.6 +/- 3.1 nA for putative type S]. 3. However, when the values of IN at threshold for repetitive firing were estimated, the distribution of IN from the red nucleus was quite different. At threshold, all of the putative type S units received hyperpolarizing IN but so did nearly half of the putative type F units. 4. As would be expected from the wide range of IN at threshold (-20 to +12 nA), the red nucleus input produced dramatically different effects on the discharge of different motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidromic and synaptic activation of Deiters' neurons induced by stimulation of red nucleus in the cat

Antidromic and orthodromic action potentials of neurons located in the lateral vestibular nucleus of Deiters' evoked by stimulation of red nucleus were studied in anaesthetized cats. Vestibulospinal neurons were identified by stimulation of the lateral vestibulospinal tract. The ‘second-order’ vestibular neurons were revealed by mean of stimulation of the ipsilateral VIIIth nerve. Stimulation of the red nucleus is shown to lead mainly to antidromic, as well as mono-, oligo- and polysynaptic activation of Deiters' neurons. Not any inhibitory reaction was observed in vestibular neurons in response to stimulation of the red nucleus. Ascending axon collaterals of the vestibulospinal neurons to this brainstem structure were revealed. The peculiarities and functional significance of the effects mentioned are discussed.

Mechanisms of supraspinal correction of scratching generator

The influences of signals in descending systems on the parameters of scratching generator activity were studied on decerebrate immobilized cats. It was shown that phasic electric stimulation of descending systems evoked certain phase-dependent reorganization of the parameters of scratching generator efferent activity. Maximum increase in scratching cycle duration during electric stimulation of Deiters' nucleus, red nucleus and pyramidal tract is observed during stimulation in the first half of aiming phase. Stimulation in the second half of aiming phase and at the beginning of scratching jerk phase virtually does not change the scratching cycle duration. Maximum increase in scratching cycle duration during electric stimulation of the nucleus reticularis gigantocellularis is observed in the second half of aiming phase. Electric activation of descending pathways during aiming phase increases its intensity and decreases the intensity of scratching jerk phase. Activation of descending pathways during scratching jerk phase increases its intensity and virtually does not change the aiming phase intensity. Influences of electric activation of descending systems on scratching generator work reveal dependence on limb position. They are increased when the limb is deflected to the rear and are decreased during over-aimed position. Decerebellation leads to a decrease of scratching generator activity parameters rearrangement under influence of electric stimulation of the red nucleus and nucleus reticularis gigantocellularis, and to its increase during Deiters' nucleus stimulation. On the basis of these results the principles of supraspinal correction of scratching generator work are discussed.

Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine-induced injury of dopaminergic nigrostriatal system on movement components of the instrumental reflex and motor thalamic neurons' reactions in the cat

Peculiarities of excitation and inhibition in ventral lateral and ventral anterior thalamic neurons were studied in cats with movement disorders (bradykinesia and muscle rigidity) induced by injury of nigrostriatal dopaminergic neurons with neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (5 mg/kg daily, intramuscularly for five days). As was shown in chronic experiments, mean discharge frequency of neurons related to initiation of upper limb movements increased. Excitation of these neurons coincided with movement initiation, flexion and extension becoming more prominent and prolonged as compared with normal animals. In parallel to those changes, bradykinesia developed. In acute experiments performed under ketalar anaesthesia and myorelaxine immobilization it was found that neurotoxin caused a decrease of the inhibition duration and effectiveness in relay and non-relay thalamic motor nuclei neurons. The inhibition deficiency was accompanied by a shortening of latencies of orthodromic responses evoked by red nucleus stimulation. Two days after the last neurotoxin injection, light microscope examination revealed that about 48% of neurons located in the pars compacta of substantia nigra were destroyed. Electron microscopic analysis showed hydropic changes in perykaria and dendrites in most neurons of the substantia nigra pars compacta that are typical of the light type of degeneration. Pathomorphological processes in the synaptic apparatus were also found. The content of dopamine in the caudate nucleus fell to 30% as compared with intact animals. The suggestion is made that the deficiency of inhibition developed in motor thalamic neurons in response to nigrostriatal system destruction results from attenuation of dopamine-modulated direct GABAergic nigrothalamic influences and/or might be connected with increased inhibition of inhibitory interneurons of the same thalamic nuclei conditioned by pallidum disinhibition.

Inhibition of sensory responses of cat inferior olive neurons produced by stimulation of red nucleus

1. The sensory responsiveness of cells in the inferior olive is known to be suppressed during certain phases of active movement. These experiments were designed to test the possibility that activity in the rubrospinal pathway contributes to this suppression. We recorded from cells sensitive to light touch located in one of the divisions of the inferior olive, the rostral dorsal accessory olive (rDAO), in cats anesthetized with pentobarbitol sodium. Responsiveness to peripheral stimuli was tested during and after trains of conditioning stimuli delivered to the rubrospinal pathway. 2. All 44 cells in our sample of rDAO neurons showed an inhibition of responsiveness to peripheral stimuli after conditioning stimulation of the rubrospinal pathway. Typical conditioning trains consisted of 0.2-ms pulses at 200 Hz for 100 ms. The mean current required for a reduction in firing probability to 0.5 was 31 microA. Slight increases in intensity often completely inhibited responses to peripheral stimuli. 3. Inhibition of responsiveness showed a delayed time course. Peak inhibition occurred approximately 50 ms after the last pulse in the conditioning train. In many cases there was no demonstrable inhibition during the conditioning train. Increases of train frequency, train duration, or stimulus intensity produced stronger and broader periods of olivary inhibition. 4. The lowest threshold points for eliciting rDAO inhibition coincided with either the magnocellular red nucleus (RNm) or the rubrospinal tract (RST). Stimulation at RST sites produced inhibition of responses in the contralateral but not in the ipsilateral rDAO. Transection of the RST in the upper brain stem blocked the inhibition produced by red-nucleus stimulation without altering the inhibition produced by tract stimulation caudal to the transection. The inhibitory effects thus appear to be caused by activation of the rubrospinal pathway. 5. The inhibitory timing observed in this study may be appropriate for explaining the suppression of olivary responsiveness to contact that has been observed in awake animals. Bursts of movement-related, red nucleus discharge often cease approximately 50 ms before the end of movement. This timing would allow peak inhibition to develop at approximately the time of contact with an object at the end of a goal-directed limb movement.

Inhibitory and excitatory processes in thalamic motor nuclei neurons in the normal nigrostriatal dopaminergic system and following injury to it produced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Excitatory and inhibitory processes in neurons of the thalamic anteroventral and ventrolateral (VA–VL) motor nuclei were investigated in two sets of experiments on cats anesthetized with Ketalar and immobilized by myorelaxant during the course of stimulation of the red nucleus region and following chronic administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5 mg/kg i.m. over a 5-day period): It was found 48 h after the last MPTP injection that up to 48% neurons belonging to the substantia nigra pars compacta had been destroyed and that dopamine level had declined to 30% of that found in intact animals. In cats injected with MPTP inhibitory processes declined significantly in both duration and efficacy in VA–VL relay and non-relay neurons, while latency of orthodromic excitatory response to red nucleus stimulation declined. It is suggested that attenuation of dopamine-modulated GABA-ergic nigrothalamic influences underlies the low level of inhibition occurring.

Effect of stimulation in three subcortical sites on the thalamocortical augmenting response in the cat.

The thalamocortical augmenting response is a complex multineuronal response which can be elicited by repetitive stimulation of the ventrolateral thalamus. A major function of the ventrolateral thalamus is known to be a result of its participation in central nervous system activity related to motor behaviour. The significance of the thalamocortical augmenting response itself is not known. Since it would be reasonable to relate that response to motor behaviour, we evaluated the effect on the thalamocortical augmenting response of the stimulation of two other central nervous system structures which are also thought to participate in motor control, the cerebellum and the red nucleus. We conclude that at least part of the effect of red nucleus stimulation on the thalamocortical augmenting response is exerted through a rubro-olivo-cerebellar pathway. We then compared the effects of red nucleus and of cerebellar stimulation to the effect of stimulating a non-motor mesencephalic site, the periaqueductal gray. The changes induced in the thalamocortical augmenting response appear not to be fully explicable solely in terms of changes in motor behaviour.

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.

Modulatory influences of red nucleus stimulation on the somatosensory responses of cat trigeminal subnucleus oralis neurons

Little is known of the effect of red nucleus (RN) stimulation on somatosensory neurons despite its known anatomic projections to somatosensory relay nuclei. The effect of RN stimulation on the somatosensory responses of trigeminal subnucleus oralis (Vo) neurons was investigated in chloralose- or barbiturate-anesthetized cats. Arrays of bipolar stimulating electrodes were inserted into the contralateral and ipsilateral RN and the contralateral thalamus. Extracellular single-unit recordings were obtained in Vo with tungsten microelectrodes. Neurons in Vo were excited to just suprathreshold by electrical stimulation within their receptive fields. Red nucleus influences were studied by applying 100-ms, 500-Hz conditioning trains to the contralateral or ipsilateral RN 130 ms prior to the peripheral test stimulus. The effect of RN stimulation was also tested on mechanically evoked responses of Vo cells. The somatosensory responses of most cells ( 70 73 ) were inhibited after RN stimulation. Some of these cells ( 15 70 ) could be antidromically activated from the contralateral thalamus. Stimulation of the RN resulted in excitation followed by inhibition in nine Vo cells. The results suggest that the RN may modulate transmission of somatosensory information through Vo.

Long duration antinociception induced by red nucleus stimulation in the rat

1Department of Pharmacology, MRP, Ribeirao Preto, Brazil (CNPq Fellow) 2Department of Pharmacology, CDRI, Lucknow, India (Wellcome Trust Fellow) 3Department of Pharmacology, Physiology, University College, Cardiff, U.K.

Supraspinal facilitation of cutaneous polysynaptic EPSPs in cat medical gastrocnemius motoneurons.

We examined the characteristics of postsynaptic potentials (PSPs) produced in antidromically-identified medical gastrocnemius (MG) alpha-motoneurons by electrical stimulation of low threshold (less than 3 x T) distal limb cutaneous afferents in the sural (SUR) nerve in adult cats anesthetized with alpha-chloralose, together with the effects of SUR PSPs of supraspinal conditioning stimulation of the contralateral red nucleus (RN) and pyramidal tract (PT). In the majority of MG motoneurons, SUR afferents with electrical thresholds less than 1.5 x T produced early excitatory synaptic potentials (EPSPs) with minimum central latency of about 2.0 ms, suggesting activation of a trisynaptic segmental pathway with two interposed interneurons. Such early EPSPs were often detectable with stimuli less than 1.2 x T, as determined by recording the compound action potential in the sciatic nerve and from the first appearance of the N1 wave of the cord dorsum potential. Inhibitory synaptic potentials (IPSPs) were regularly produced by SUR volleys of only slightly greater strength (often as low as 1.3 x T) and these had minimum central latencies of about 3.0 ms (about 1.0 ms longer than the earliest EPSPs), suggesting a three interneuron central pathway. Repetitive stimulation of RN and PT regularly produced facilitation of both EPSP and IPSP components in the SUR response, suggesting that these supraspinal systems directly or indirectly excite some of the same interneurons that convey the SUR effects to MG motoneurons. When using very low strength SUR stimuli, PT conditioning produced relatively pure facilitation of the SUR EPSPs but with larger SUr volleys, PT clearly facilitated both EPSPs and IPSPs. RN conditioning produced more parallel facilitation of SUR EPSPs and IPSPs. Supraspinal control of the polysynaptic pathway producing SUR EPSPs is of particular interest because of earlier evidence that this pathway is differentially distributed to motoneurons of fast twitch versus slow twitch MG motor units.

Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). I. Responses to oral-facial noxious and nonnoxious stimuli and projections to thalamus and subnucleus oralis.

Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). I. Responses to oral-facial noxious and nonnoxious stimuli and projections to thalamus and subnucleus oralis.

Sensory transmission through lemniscal pathway during voluntary movement in the cat.

Sensory transmission through lemniscal pathway during voluntary movement in the cat.

Corticoreticulospinal control of the tonic vibration reflex in the cat

The cortico-reticulospinal system has been investigated using vibration to produce a tonic reflex in an intact cat. Stimulation of the motor cortex potentiated the effects of medial medullary inhibition but not the facilitation evoked from the lateral medulla. The cortico-bulboreticular pathways were found to project bilaterally to the medulla. Medullary stimulation produced bilateral facilitation or inhibition of the tonic vibration reflex (TVR). Although the cortico-bulboreticular pathway projected bilaterally the effect evoked from the motor cortex was clearly contralateral in its end result. The cortico-reticulospinal system usually inhibits the tonic vibration reflex of both triceps surae and tibialis anterior, but on occasions inhibition of triceps surae was accompanied by a phasic contraction of the tibialis anterior. Stimulation of the contralateral caudate nucleus failed to influence the TVR directly or the response evoked by medullary stimulation. Stimulation of the contralateral red nucleus evoked a facilitation of the TVR which continued several seconds after red nucleus stimulation ceased. It was concluded that those medullary neurones which inhibit tone in flexor and extensor hind limb muscles of the cat are controlled directly by the motor cortex and are uninfluenced by caudate nucleus or red nucleus. The facilitatory neurones in the lateral medulla appear to be independent of cortical control.