Suppression of dental pulp-evoked trigeminal responses by nucleus reticularis gigantocellularis in the cat.

The temporal effect of electrical stimulation of the nucleus reticularis giganto-cellularis (NRGC) on the dental pulp-evoked field potential in the subnucleus oralis of the spinal trigeminal complex (oralis potential) and on the jaw-opening reflex was investigated in precollicular decrebrate cats using the conditioning-testing technique. NRGC activation invariably elicited suppression of the oralis potential, the degree and duration of which were related to the reticular stimulus parameters. When activated at optimal stimulus parameters, NRGC was found to exert parallel inhibition of oralis potential and jaw-opening reflex lasting 500 to 800 ms in many instances. The possibility that NRGC may interrupt the transmission of noxious signals from the dental pulp by promoting a depolarization of pulpal afferents is discussed in light of the current concepts on opiate receptors and their ligands and parallel studies in this laboratory.     

Antagonization of clonidine- and morphine-promoted antinociception by kainic acid lesion of nucleus reticularis gigantocellularis in the rat

We evaluated the participation of nucleus reticularis gigantocellularis (NRGC) in clonidine- and morphine-induced analgesia in young rats, using the hot-plate assay as the nociceptive test. Bilateral kainic acid lesion of the NRGC did not alter the baseline pain responses to noxious heat stimulus. Selective destruction of the NRGC neuronal perikarya, however, significantly attenuated the analgesic efficacy of an optimal dose of clonidine or morphine. Sham-lesion animals, on the other hand, showed no appreciable alteration in the antinociceptive potency of both the imidazoline compound and the opiate. We conclude that the NRGC may be a critical central site for clonidine- and morphine-promoted pain inhibition, although this reticular nucleus did not appear to function as a tonically active endogenous analgesic mechanism. The incomplete elimination of morphine-elicited antinociception by NRGC lesion confirmed the engagement of other neural substrates in the process. We discuss whether NRGC participates in pain suppression by the opiate in parallel or in series to these other central sites.     

Collateralization of reticulospinal axons from the nucleus reticularis gigantocellularis to the cerebellum and diencephalon. A double-labelling study in the rat

Use of True blue and Nuclear yellow in double labelling experiments reveals that, in the rat, neurons of the nucleus reticularis gigantocellularis which innervate the spinal cord, cerebellum and diencephalon, are present in at least partially overlapping areas. However, relatively few reticulospinal neurons provide collaterals to either the cerebellum or diencephalon.     

Neuronal receptive field properties in feline nucleus reticularis gigantocellularis

Nucleus reticularis gigantocellularis (NGC) has been shown, using both behavioral and physiological techniques, to be involved in the processing of nociceptive information. However, previous studies of the receptive fields of NGC neurons have utilized only innocuous stimuli. Thus, while neurons in NGC may play an important role in nociception, the receptive field properties of these cells remain to be defined. This investigation was designed to determine the receptive field properties of neurons in NGC using nociceptive and innocuous stimuli. Receptive fields were determined for 127 neurons in NGC. Eighty-seven percent of the NGC neurons studied responded exclusively to noxious stimuli, while 13% also responded to innocuous stimuli. None of the neurons studied responded exclusively to innocuous stimuli. The receptive fields of most NGC neurons (63%) were large, discontinuous, and bilaterally symmetrical. Eighty-one percent of NGC neurons received convergent inputs from both spinal and trigeminal systems. These receptive field properties differ from those previously reported using only innocuous stimulation     

Lesion in nucleus reticularis gigantocellularis: effect on the antinociception produced by micro-injection of morphine and focal electrical stimulation in the periaqueductal gray matter

The effect of bilateral electrolytic lesions in the nucleus reticularis giganto-cellularis (NGC) on the antinociceptive efficacy of morphine and electrical stimulation applied in the periaqueductal central gray matter (PAG) was investigated. Antinociception, evaluated by standard hot plate and tail-flick analgesiometric tests, was reliably produced by morphine (5 microgram) and focal electrical stimulation (40-200 micro A) administered in the PAG of rats via chronic indwelling cannula/electrode assemblies. Subsequent to the initial antinociceptive testing, bilateral electrolytic lesions were introduced in the NGC and the antinociceptive efficacy of morphine and stimulation in the PAG was again evaluated. Lesions in the NGC prevented the expression of the antinociception produced by the microinjection of morphine in the PAG whereas the antinociception resulting from electrical stimulation in the PAG was unaffected. Further, lesions in the NGC did not alter baseline (control) nociceptive thresholds in either analgesiometric test. These results provide additional support for involvement of the NGC in morphine-induced antinociception and, in addition, suggest that the NGC is not essential to a tonically-active inhibitory system or to the antinociception produced by focal electrical stimulation in the PAG.     

Noxious stimuli and Met-enkephalin release from nucleus reticularis gigantocellularis

The nucleus reticularis gigantocellularis of the rat medulla oblongata was perfused in situ, and effects of noxious stimuli on the release of immunoreactive Met-enkephalin were examined. Formalin-induced and thermal but not mechanical stimuli increased the "tonic" release of immunoreactive Met-enkephalin from this nucleus. No "phasic" increase was observed following the three forms of stimulation. A topical application of dibucaine abolished the formalin-induced increase in the release of immunoreactive Met-enkephalin. Therefore, the possibility that persistent noxious stimuli may activate the Met-enkephalin-containing fibers in the nucleus reticularis gigantocellularis has to be given consideration.     

Spinal serotonin receptors mediate descending facilitation of a nociceptive reflex from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat

Electrical stimulation in the nucleus reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha) produces facilitation and/or inhibition of spinal nociceptive transmission in behavioral and electrophysiological studies. The present study examined spinal neurotransmitter receptors mediating descending facilitation from the NGC/NGC alpha. As previously demonstrated, electrical stimulation in the NGC/NGC alpha at low intensities (approximately equal to 10 microA) produced facilitation and at greater intensities (approximately equal to 38 microA) inhibition of the tail-flick (TF) reflex. Intrathecal pretreatment with the non-selective serotonin (5-HT) receptor antagonist methysergide attenuated or completely abolished facilitation of the TF reflex produced by electrical stimulation in the NGC/NGC alpha; intrathecal pretreatment with atropine, phentolamine, naloxone or mecamylamine was without effect on stimulation-produced facilitation. Descending inhibition from the NGC/NGC alpha produced by electrical stimulation was attenuated or completely abolished by bilateral transection of the dorsolateral funiculi (DLF) of the cervical spinal cord. Descending facilitation produced by electrical stimulation, however, was unaffected or enhanced following DLF transections. Glutamate microinjections (1.7 nmol/0.17 microliters) into the NGC/NGC alpha produced a rapid, repeatable and short-duration facilitation of the TF reflex in rats with bilateral DLF transections and such facilitation was attenuated by intrathecal pretreatment with methysergide, but not atropine, xylamidine (5-HT2 selective receptor antagonist) or MDL-72222 (5-HT3 selective receptor antagonist). These findings suggest that facilitation of the TF reflex from the activation of the cell bodies in the NGC/NGC alpha is mediated by a descending serotonergic pathway traveling in the ventrolateral funiculi and by spinal 5-HT1 receptors.     

Activity changes in nucleus reticularis gigantocellularis in relation to skilled forelimb movement in rats

Adult hooded rats were trained to reach for food pellets into a narrow plexiglass tube and the movement of the preferred forelimb was photo-electrically detected. Multiple unit activity (MUA) or single unit activity in n. reticularis gigantocellularis (NGC) was recorded during reaching. Depression of MUA was observed about the onset of the forepaw movement and lasted during its execution. There was a correlation between MUA changes and the depression of activity of individual neurons observed in a part of NGC.     

Effect of stimulation of the nucleus reticularis gigantocellularis on the membrane potential of cat lumbar motoneurons during sleep and wakefulness

The present study was performed in order to determine the effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the membrane potential of spinal cord motoneurons during sleep and wakefulness. Accordingly, intracellular recordings were obtained from lumbar motoneurons in unanesthetized normally respiring cats during naturally occurring states of wakefulness, quiet sleep and active sleep. Electrical stimuli applied to the NRGc evoked synaptic potentials which occurred at short latency (<10ms) and did not exhibit consistent changes in their waveforms during any states of sleep or wakefulness. During wakefulness and quiet sleep, longer latency (20ms) low-amplitude hyperpolarizing potentials occasionally followed NRGc stimulation. However, during active sleep, NRGc stimulation produced,in all motoneurons, relatively large hyperpolarizing potentials that were characterized by a mean amplitude of3.5±0.4mV(mean±S.E.M.), a mean latency-to-peak of43.0±0.8ms, and an average duration of34.4±1.7ms. These potentials were capable of blocking the generation of orthodromic spikes elicited by sciatic nerve stimulation. When anodal current or chloride was passed through the recording electrode, the hyperpolarizing potentials decreased in amplitude, and in some cases their polarity was reversed. These results indicate that the active sleep-specific hyperpolarizing potentials were inhibitory postsynaptic potentials. Thus, the NRGc possesses the capability of providing a postsynaptic inhibitory drive that is directed toward lumbar motoneurons which is dependent on the occurrence of the behavioral state of active sleep. These data suggest that the NRGc may be an important link in the brainstem-spinal cord system that is responsible, during active sleep, for the postsynaptic inhibition of lumbar motoneurons.     

The location of brainstem neurons which project bilaterally to the spinal trigeminal nuclei as demonstrated by the double fluorescent retrograde tracer technique

Cells with possible dual projections to both spinal trigeminal nuclei were identified in the rat brainstem following separate injections of different retrogradely transported markers into the right and left spinal trigeminal nucleus. The greatest number of double-labeled cells was located in the nucleus reticularis gigantocellularis. Several double-marked cells were also observed in the nucleus raphe magnus, the nucleus paragigantocellularis and the periaqueductal gray. These results suggest that some cells in the above brainstem nuclei may have a bilateral modulating effect on the spinal trigeminal nuclei.     

The location of brainstem neurons which project bilaterally to the spinal trigeminal nuclei as demonstrated by the double flourescent retrograde tracer technique

Cells with possible dual projections to both spinal trigeminal nuclei were identified in the rat brainstem following separate injections of different retrogradely transported markers into the right and left spinal trigeminal nucleus. The greatest number of double-labeled cells was located in the nucleus reticularis gigantocellularis. Several double-marked were also observed in the nucleus raphe magnus, the nucleus paragigantocellularis and the periaqueductal gray. These results suggest that some cells in the above brainstem nuclei may have a bilateral modulating effect on the spinal trigeminal nuclei.     

Dendrodendritic synapses in the cat reticularis thalami nucleus: a structural basis for thalamic spindle synchronization

Dendrodentritic synapses have been found between the dendrites of reticularis thalami neurons. These synapses were symmetric and the presynaptic element contained pleomorphic vesicles. A few cases of reciprocal dendrodendritic synapses were also observed. Given the morphological features of the synapses and the well-established GABAergic nature of reticularis neurons it is concluded that reticularis cell dendrites form a local inhibitory network. The functional implications of this type of organization for the synchronization of spindle oscillations are discussed and a new hypothesis is proposed.     

Reinstatement of festinating forward locomotion by antiserotonergic drugs in rats partially recovered from damage in the region of the nucleus reticularis tegmenti pontis

Damage in the region of the nucleus reticularis tegmenti pontis (NRTP) produces galloping festinating forward locomotion. Therefore, the NRTP is part of a system that normally inhibits locomotion. In operated rats that had partially recovered the ability to inhibit locomotion, presumably based on recovery of function in that inhibitory system, methysergide (45 or 60 mg/kg) or metergoline (5 or 10 mg/kg) reinstated such galloping. This suggests that serotonin systems blocked by these drugs may activate this system to inhibit locomotion. In haloperidol akinesia (a model of parkinsonian akinesia), NRTP destruction or inactivation also released festinating locomotion (3). We suggest that dopamine deficiency-induced akinesia may result from the unchecked action of the NRTP movement-inhibition system. This agrees with earlier findings by us that lateral hypothalamic damage-induced profound akinesia can be reversed by methysergide (4). Antiserotonergic drugs may therefore prove useful in alleviating parkinsonian akinesia.     

Population synaptic potentials evoked in lumbar motoneurons following stimulation of the nucleus reticularis gigantocellularis during carbachol-induced atonia

The effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on lumbar spinal cord motoneurons was studied in the decerebrate cat using sucrose-gap recordings from ventral roots. The NRGc was stimulated ipsi- and contralaterally before and during atonia elicited by the microinjection of carbachol into the pontine reticular formation. Prior to carbachol administration, the NRGc-induced response recorded from the sucrose-gap consisted of two consecutive excitatory population synaptic potentials followed by a long-lasting, smallamplitude inhibitory population synaptic potential. Following carbachol injection, the same NRGc stimulus evoked a distinct, large amplitude inhibitory population synaptic potential, whereas the excitatory population synaptic potentials decreased in amplitude. In addition, after carbachol administration, the amplitude of the monosynaptic excitatory population synaptic potential, which was evoked by stimulation of group Ia afferents in hindlimb nerves, was reduced by 18 to 43%. When evoked at the peak of the NRGc-induced inhibitory response, this potential was further decreased in amplitude. Systemic strychnine administration (0.07–0.1 mg/kg, i.v.) blocked the NRGc-induced inhibitory population synaptic potential and promoted an increase in the amplitude of the excitatory population synaptic potentials induced by stimulation of the NRGc and group Ia afferents. These data indicate that during the state of carbachol-induced atonia, the NRGc effects on ipsi- and contralateral spinal cord motoneurons are predominantly inhibitory and that glycine is likely to be involved in this inhibitory process. These results support the hypothesis that the nucleus reticularis gigantocellularis is part of the system responsible for state-dependent somatomotor inhibition that occurs during active sleep.     

Response patterns of cells in the feline caudal nucleus reticularis gigantocellularis after noxious trigeminal and spinal stimulation

Nucleus reticularis gigantocellularis has been shown, using both behavioral and physiological techniques, to be involved in the processing of nociceptive information in spinal systems. This investigation was designed to characterize the response patterns of nucleus reticularis gigantocellularis neurons to both spinal (superficial radial and sciatic nerve) and trigeminal (tooth pulp) noxious stimuli. One hundred and sixty-two neurons were studied using a poststimulus-time histogram analysis. Neurons in nucleus reticularis gigantocellularis were classified in four categories based on their responses to noxious stimuli: (i) 51% of the neurons responded to noxious stimuli delivered to all stimulus sites noted above with a short-latency, short-duration excitatory period, followed by a long-duration period of suppressed activity relative to control levels (“E-S cells”); (ii) 25% of the neurons studied responded to all noxious stimuli tested only with an excitatory response (“E cells”); (iii) 6% of the neurons responded to all noxious stimuli only with a period of suppressed activity (“S cells”) (some S cells had a period of increased activity after the period of suppression); (iv) 18% of the neurons had mixed responses, with the response depending on the site of stimulation (“M cells”). Except for M cells, each cell tended to respond with a characteristic response pattern, regardless of the site of stimulation.     

Postsynaptic inhibition of cat medullary dorsal horn neurons by stimulation of nucleus raphe magnus and other brain stem sites

Sensory responses of neurons in the medullary and spinal cord dorsal horn can be inhibited by stimulation of a number of brain stem regions. These regions include the nucleus raphe magnus (NRM), the nucleus reticularis gigantocellularis (NGC), the nucleus reticularis magnocellularis (NMC), the periaqueductal gray (PAG), and the nucleus cuneiformis (CU). The purpose of this study was to determine whether or not this inhibition is mediated by postsynaptic processes. Experiments were carried out on chloralose-anesthetized cats. The responses of 29 medullary dorsal horn (trigeminal subnucleus caudalis) cells were recorded with carbon-fiber microelectrodes. Included were cells which responded to noxious stimulation (nine cells) as well as cells which responded only to nonnoxious input. The presence of postsynaptic inhibition was tested by two indirect techniques. We studied the effects of conditioning stimulation of the five regions on the latency of antidromically activated cells and also on the firing rate of neurons excited by iontophoretically applied glutamate. Conditioning stimulation was associated with a block or increased latency of antidromic activation in 15 of 18 nociceptive and nonnociceptive neurons. These effects reflect membrane hyperpolarization, presumably resulting from postsynaptic inhibition. Furthermore, conditioning stimulation of these regions inhibited the glutamate-evoked firing of all 11 cells tested, also indicating a postsynaptic type of inhibition of medullary dorsal horn cells. Thus these results indicate that at least part of the inhibition induced by stimulation of the NRM, NGC, NMC, PAG, and the CU probably results from postsynaptic inhibitory mechanisms.     

Edinger-Westphal nucleus: cholecystokinin immunocytochemistry and projections to spinal cord and trigeminal nucleus in the cat

Immunocytochemical methods were used to determine the distribution of cells with cholecystokinin-like immunoreactivity (CCK-LI) in the cat Edinger-Westphal complex (EW). Numerous cells with CCK-LI are found throughout the length of EW. The distribution and frequency of such cells are similar to the pattern of EW neurons that show substance P-like immunoreactivity (SP-LI). Companion retrograde transport experiments reveal that EW neurons which project to spinal cord or the region of the caudal trigeminal nucleus are found throughout the length of EW, and that some EW neurons which project to spinal cord also show CCK-LI.     

Effect of inhibitory amino acid antagonists on IPSPs induced in lumbar motoneurons upon stimulation of the nucleus reticularis gigantocellularis during active sleep

The present study was performed to generate data implicating glycine or γ-aminobutyric acid as neurotransmitter candidates mediating the IPSPs which are recorded in lumbar motoneurons following electrical stimulation of the nucleus reticularis gigantocellularis (NRGc) during the atonia of active sleep. Accordingly, intracellular records were obtained from lumbar motoneurons in unanesthetized, normally respiring cats during naturally occurring states of active sleep, while inhibitory amino acid antagonists were microiontophoretically released next to the recorded cell. Electrical stimuli, applied to the NRGc during active sleep under drug-free conditions, evoked inhibitory postsynaptic potentials (IPSPs) in all of the lumbar motoneurons which were examined. These NRGc-induced IPSPs exhibited an average latency-to-onset of 26.6 ± 1.3 ms, a latency-to-peak of 42.5 ± 1.3 ms, an average amplitude of 3.9 ± 0.4 mV and a duration of 34.4 ± 2.1 ms. Strychnine, when applied microiontophoretically, abolished or markedly suppressed these NRGc-induced IPSPs. In contrast, the microiontophoretic application of picrotoxin or bicuculline methiodide failed to block these IPSPs. To the extent that strychnine may be considered to be a specific antagonist of glycine, the present results suggest that glycine (or a structurally related amino acid) participates in the generation of NRGc-induced IPSPs during the atonia of active sleep.     

Somatotopic organization of nucleus reticularis thalami in chronic awake cats and monkeys

Responses of cells in the nucleus reticularis thalami (nRT) to peripheral stimulation were studied in chronic cats and monkeys. The activities were recorded through glass micropipettes. Natural stimulation as well as electric stimulation of implanted nerves were employed in 5 cats and 2 monkeys.

In the nRT, 30% of the cells studies in the cat and 60% in the monkey were driven by non-noxious stimulations. A topical organization was demonstrated; however, it is not as precise as that shown for the ventrobasalis (VB) nucleus. The size of peripheral fields was larger than that of cells in the VB nucleus. The modalities of activation of these cells were similar to those of the different specific thalamic nuclei.

The mean response latency to peripheral stimulation was longer and the fluctuation in the latency more important than those of the specific thalamic relay. The observations lend support to the hypothesis that most, if not all, of then nRT neurons are innervated by axon collaterals of the thalamocortical or corticathalamic bundles. Burst activities were not numerous in chronic cats (12%) and scarce in monkeys. These bursting neurons are mainly found in the perigeniculate area.     

Electrophysiological study of the nucleus of the optic tract that transfers optic signals to the nucleus reticularis tegmenti pontis—the visual mossy fiber pathway to the cerebellar flocculus

Neuronal activities (n = 43) in the pretectal region in rabbits were recorded. They were orthodromically activated from the optic chiasm (latency, 1.86 ± 0.35msec) and antidromically from the ipsilateral nucleus reticularis tegmenti pontis (Nrt) (latency, 0.97 ± 0.22sec). Thirty-one (72%) neurons were in the nucleus of the optic tract (NOT), four (9%) in the anterior pretectal nucleus (PA) and seven (16%) in the border between NOT and PA. These findings demonstrate that the NOT is involved in the visual mossy fiber pathways to the flocculus and may contribute to optokinetic eye movements.