Stimulation Of Nucleus Reticularis Gigantocellularis Research Articles

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms

Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.

Depression of Spinal Sensory Transmission During REM Sleep: Dopaminergic Involvement and Insights Into Restless Legs Syndrome. Focus on “State-Dependent Changes in Glutamate, Glycine, GABA, and Dopamine Levels in Cat Lumbar Spinal Cord”

Rapid-eye-movement (REM) sleep is also called paradoxical sleep because brain electroencephalographic (EEG) activity is similar to wakefulness. Aside from the obvious, one distinction between wakefulness and paradoxical sleep is the central suppression of both somatosensory and motor activity. The mechanisms that control these state-dependent changes appear to involve bulbospinal systems, while the contribution of diencephalospinal dopaminergic projections are not known. A recent article by Taepavarapruk et al. employed in vivo microdialysis and high-performance liquid chromatography (HPLC) analysis techniques to provide the first evidence of spinal cord amino acid transmitter and dopamine release related to these descending systems during naturally occurring sleep/wake cycles. The authors measured release in the vicinity of two ascending tracts, the dorsal spinocerebellar tract (DSCT; Clarke’s column) and the spinoreticular tract. Both tracts receive multiconvergent sensory input from numerous sensory qualities. The DSCT is a major relay point for the processing of spinal proprioceptive sensory information (Bosco and Poppele 2001) while the spinoreticular tract (SRT) also encodes nociceptive stimuli (Willis. and Coggeshall 1991). Naturally occurring release profiles were also compared with that seen during stimulation of the nucleus reticularis gigantocellularis (NRGc), an area known to inhibit both motoneurons and activity in the aforementioned ascending tracts. The authors tested whether changes in transmitter release during REM sleep are associated with the known reduction of sensory inflow to higher brain centers via the DSCT and SRT. When compared with wakefulness, whether during REM sleep or following NRGc stimulation, glutamate and glycine levels increased identically (48 or 69%, respectively) supporting release by common mechanisms. The neural pathways involved in this process therefore likely include reticulospinal and local interneuronal systems. In comparison, GABA levels increased only modestly during REM sleep and not at all following NRGc stimulation. More intriguingly, the authors also showed that dopamine levels significantly decreased during REM sleep when compared with wakefulness. Spinal dopamine is derived from the A11 dopaminergic nucleus of the dorsoposterior hypothalamus

Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. II. Effects on metrics and kinematics of ongoing gaze shifts to visual targets.

Saccade kinematics are altered by ongoing head movements. The hypothesis that a head movement command signal, proportional to head velocity, transiently reduces the gain of the saccadic burst generator (Freedman 2001, Biol Cybern 84:453-462) can account for this observation. Using electrical stimulation of the rhesus monkey nucleus reticularis gigantocellularis (NRG) to alter the head contribution to ongoing gaze shifts, two critical predictions of this gaze control hypothesis were tested. First, this hypothesis predicts that activation of the head command pathway will cause a transient reduction in the gain of the saccadic burst generator. This should alter saccade kinematics by initially reducing velocity without altering saccade amplitude. Second, because this hypothesis does not assume that gaze amplitude is controlled via feedback, the added head contribution (produced by NRG stimulation on the side ipsilateral to the direction of an ongoing gaze shift) should lead to hypermetric gaze shifts. At every stimulation site tested, saccade kinematics were systematically altered in a way that was consistent with transient reduction of the gain of the saccadic burst generator. In addition, gaze shifts produced during NRG stimulation were hypermetric compared with control movements. For example, when targets were briefly flashed 30 degrees from an initial fixation location, gaze shifts during NRG stimulation were on average 140% larger than control movements. These data are consistent with the predictions of the tested hypothesis, and may be problematic for gaze control models that rely on feedback control of gaze amplitude, as well as for models that do not posit an interaction between head commands and the saccade burst generator.

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.

Involvement of the raphe in the respiratory effects of gigantocellular area activation

Previous reports indicate that the nucleus reticularis gigantocellularis (NGC) of the brainstem reticular formation is involved in inhibitory respiratory and cardiovascular reflexes. Stimulation of portions of the nearby bulbar raphe complex, specifically the raphe magnus (RM), have also been shown to suppress phrenic activity and to decrease blood pressure and heart rate. Since synaptic connectivity between the NGC and the RM has been demonstrated, we hypothesized that the RM may be involved in the cardiopulmonary effects of NGC stimulation. This study found that electrolytic lesions in the raphe magnus attenuated the inhibitory respiratory effects but not the cardiovascular suppression due to NGC stimulation. Lesions in the raphe magnus also lowered resting blood pressure and resting breath frequency. We conclude that the RM may mediate part of the NGC-mediated respiratory effects.

Medullary control of lumbar motoneurons during carbachol-induced motor inhibition

The present study examined the effects of stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the Ia-monosynaptic reflex and the membrane potential of lumbar motoneurons. Stimulation of the NRGc was carried out in acute decerebrate cats during motor suppression induced by the intrapontine microinjection of carbachol. During carbachol-induced motor suppression, compared with control conditions (prior to the administration of carbachol), NRGc stimulation resulted in a statistically significant reduction in the Ia-monosynaptic reflex. This effect was maximal at an interval of 45 ms following NRGc stimulation. NRGc stimulation also induced, in lumbar motoneurons, a large amplitude (3.17mV± 0.36 [S.E.M.]), long duration (54.73ms± 3.52 [S.E.M.]) inhibitory postsynaptic potential whose peak coincided with the interval of maximum reflex suppression. These results suggest that carbachol activates pontine neurons that excite cells of the medullary NRGc. We believe that these medullary neurons, in addition to those of the nucleus pontis oralis (NPO) 7, participate in the modulation of the descending inhibitory pathway that is responsible for the phenomenon of response-reversal 5,15 and generalized atonia during naturally occurring active (i.e. REM) sleep.

Hedonic interactions of medial prefrontal cortex and nucleus reticularis gigantocellularis

It has been shown that ‘pure reward’ and ‘reward-escape’ sites in the lateral hypothalamus (LH) of rats respectively ameliorate and exacerbate nucleus reticularis gigantocellularis (NGC) stimulation-induced aversion 52. Conversely, the present studies found that ‘rewarding’ medial prefrontal cortex (MPFC) stimulation increased escape from NGC stimulation regardless of whether the MPFC site tested was ‘pure reward’ or ‘reward-escape’ in type. This suggested that a simple algebraic summation model of positive and negative affective processes may not adequately describe the NGC-MPFC interaction. In a subsequent study, rats were observed both to barpress less to obtain, and more to escape from, ‘rewarding’ MPFC stimulation during continuous NGC stimulation, supporting the hypothesis that the observed MPFC stimulation-mediated increase in NGC stimulation escape reflected an exacerbation of aversion. Finally, NGC stimulation was seen to increase barpressing to obtain ‘subreward’ MPFC current trains, indicating a potentiation of the reward value of such current. Results of this series of studies suggests a hedonic interaction model of NGC and MPFC characterized by reciprocal neuromodulation. The model is conceptuallized as a ‘neural opponent process’ subserving affective ‘balance’ and ‘feature enhancement’, and its possible relevance to the putative role of the MPFC in cocaine use is discussed.

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 of 3.5±0.4mV(mean±S.E.M.), a mean latency-to-peak of 43.0±0.8ms, and an average duration of 34.4±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.

Medial thalamic lesions reduce the aversion-gating action of lateral hypothalamic stimulation

Aversion that is produced supraspinally in rats by stimulation of the nucleus reticularis gigantocellularis (NGC) is reduced by concurrent stimulation of lateral hypothalamus (LH) at intensities that are otherwise non-rewarding. Electrolytic lesions of medial thalamus consistently increase the LH stimulation threshold for reducing aversion. These lesions do not alter stimulation threshold for the rewarding property of LH stimulation or the aversive property of NGC stimulation. We propose that medial thalamus is part of a forebrain aversion-gating mechanism that may be engaged by increased activity in the lateral hypothalamus.

Lateral hypothalamic stimulation gates nucleus gigantocellularis-induced aversion via a reward-independent process

A monophasic pulse-pair stimulation technique was used behaviorally to infer neurophysiological interaction between ‘reward’ sites in the lateral hypothalamus (LH) and pain-implicated nucleus reticularis gigantocellularis (NGC). Rats lever-pressed for 3 s escapes from an otherwise continuous train of 0.1 ms NGC pulses delivered every 40 ms. When pulses to the LH were interdigitated with those to NGC, inter-response latencies were significantly longer. This occurred whether LH pulses were also interrupted by each lever-press (experiment 1) or not (experiment 2). Further, the same intensities of LH stimulation which inhibited escape supported high rates of lever-pressing for 3 s LH trains during inescapable NGC stimulation even though these LH trains were not of sufficient intensity to support ‘rewarding’ lever-pressing in the absence of NGC stimulation. This finding indicates that escape-inhibition in the first two experiments was not due to interfering motor effects of LH stimulation but most probably due to LH amelioration of NGC-induced aversion. Indeed, when aversion was ameliorated by morphine, lever-pressing for sub-reward-threshold LH stimulation during inescapable NGC stimulation decreased although classical self-stimulation did not. In the escape experiments, inhibition was greatest when each NGC pulse was preceded by an LH pulse at an interval of 0.1 or 10 ms. During inescapable NGC stimulation, rates of lever-pressing for LH trains were greatest when LH pulses preceded NGC pulses again at intervals of 0.1 or 10 ms. This congruence of the temporal bimodal profiles in the response functions of these two different behavioral experiments strongly suggests that the same integrative mechanism underlies both LH inhibition of NGC escape and lever-pressing for LH trains during inescapable stimulation of NGC. Since gastric loading did not alter lever-pressing for sub-reward-threshold LH trains during inescapable NGC stimulation but did inhibit classical self-stimulation, it was concluded that the inferred common integrative mechanism mediates a supraspinal gating of aversion which is independent of the LH self-stimulation reward process.

Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis.

1. Electrical stimulation in the region of the nucleus reticularis gigantocellularis (NGc) in anesthetized monkeys inhibited or excited spinothalamic tract neurons in the lumbosacral and cervical enlargements. 2. The descending effects were generally more pronounced for activity evoked by cutaneous A-delta-fibers than for activity produced by large myelinated cutaneous afferents. Nevertheless, the responses to all types of natural stimuli used could be inhibited or facilitated. 3. The excitation from repeated brief stimulus trains to the NGc sometimes increased progressively, suggesting the existence of a positive feedback system. Occasionally, repeated stimulation of the NGc produced a progressively greater inhibition. 4. The threshold stimulus strength to elicit the inhibitory and excitatory actions was usually less than 50 microA, and in some cases less than 25 microA. The inhibition and excitation increased as the stimulus intensity was raised above the threshold value, or as the number and/or frequency of pulses in the stimulus train was increased. 5. The strongest inhibition and excitation was produced by stimulation within the NGc on either side of the brain stem. There was no obvious topographic organization of inhibitory and excitatory zones. 6. Dorsolateral tractotomies in the high cervical spinal cord did not prevent the effects of NGc stimulation, indicating that the inhibitory and excitatory pathways descend in the ventral parts of the white matter. 7. It is suggested that the inhibition and excitation are mediated by the medullary reticulospinal system.