Properties of favored patterns in spontaneous spike trains and responses of favored patterns to electroacupuncture in evoked trains.

By using 'the modified detection method', our previous study has shown that all spontaneous spike trains recorded from several areas of brain and spinal cord have favored patterns (FPs). The present study further shows that: (1) all newly detected spike trains from substantia nigra zona compacta, nucleus periventricularis hypothalami and nucleus hypothalamicus posterior also have FPs, and some spike trains from neurons in the same nucleus have a common favored pattern (CF, i.e. they share the same FP), indicating that FP and CF in spike trains are common phenomena; (2) all serial correlation coefficients of FP repetitions (in serial order) in different spike trains detected are less than 0.3 (close to 0), revealing that the repetition of FPs is a renewal process; (3) in different periods of the spike trains evoked by electroacupuncture (EA), the number of different FPs and the number of repetitions of the same representative FP either increase or decrease along with the change of firing rate. The tendencies of these changes are very similar, but after EA the repetitions of different FPs in the same spike trains change differently, showing that different (hidden) responses exist at the same time. The above results suggest that the FPs in spike trains may represent various neural codes, and 'the modified detection method of FP' can pick up more information from spike trains than the firing rate analysis, hence it is a very useful tool for the study of neural coding.     

The response of individual nucleus raphe magnus neurons to microinjections of met-enkephalin at midbrain and at bulbar loci: evidence for midbrain-bulbar convergence on individual raphe neurons

Local microinjection of met-enkephalin into both the nucleus reticularis paragigantocellularis (Pgc) and into the midbrain periaqueductal gray (PAG) altered the spontaneous discharge of many nociresponsive units in the nucleus raphe magnus (NRM) of the urethane-anesthetized rat. The activity of the majority of units (11 of 14) was suppressed following microinjections into both the PAG and Pgc. Two units showed an increase in spontaneous activity after PAG microinjections and a decrease after Pgc microinjections. One cell showed a decrease in activity after microinjection into Pgc and was unaffected by the PAG microinjection. These findings demonstrate that many nociresponsive units in NRM are affected by microinjections of met-enkephalin into both Pgc and the PAG, indicating a convergent influence of these two regions on single NRM neurons.     

Microinjection of morphine into nucleus reticularis paragigantocellularis of the rat: Suppression of noxious-evoked activity of nucleus raphe magnus neurons

Microinjection of 1 microgram of morphine into nucleus reticularis paragigantocellularis (Pgc) of anesthetized rats depressed both noxious-evoked and spontaneous activity of nociresponsive neurons in the nucleus raphe magnus (NRM). This effect was naloxone-reversible, and was not observed after control injections dorsal to Pgc. The percent change in spontaneous firing was significantly greater than the percent change in pinch-evoked firing. This reduction in NRM neuronal discharge may contribute to the antinociceptive effects produced by microinjection of morphine into Pgc.     

Hypoalgesia induced by blockade of noradrenergic projections to the raphe magnus: reversal by blockade of noradrenergic projections to the spinal cord

Previous studies have demonstrated that microinjection of noradrenergic (NA) antagonists such as phentolamine in the nucleus raphe magnus (NRM) produces hypoalgesia. This hypoalgesia appears to result from disinhibition of raphe-spinal serotonergic neurons since it is blocked by intrathecally injected methysergide. The present studies demonstrate that the hypoalgesia produced by microinjection of phentolamine in the NRM is also abolished by intrathecal administration of phentolamine. The results suggest that the hypoalgesia produced by microinjection of NA antagonists in the NRM is also mediated, at least in part, by the activation of spinally projecting NA neurons. Such hypoalgesia does not appear to be mediated by activation of enkephalinergic neurons since intrathecal injection of the opiate antagonist naloxone did not attenuate the hypoalgesia.     

Alterations in nociception following lesions of the A5 catecholamine nucleus

Neurons located in the nucleus raphe magnus (NRM), a region important in the control of nociception, appear to be tonically inhibited by noradrenergic (NA) neurons. Anatomical studies have suggested that the A5 catecholamine nucleus may be the primary source of noradrenergic neurons whose terminals are located in the NRM. The purpose of the present study was to examine the role of A5 neurons in the modulation of nociception. Bilateral electrolytic lesions of the A5 nuclei produced a marked and long lasting antinociception as assessed by both the tail-flick and hot-plate tests. Unilateral A5 lesions also produced a long-lasting elevation in hot-plate latency, but the elevation of tail-flick latency was smaller in magnitude and was only observed one day following the lesion. This finding is consistent with previous studies which have shown that blockade of the NA input to the NRM by the microinjection of NA antagonists also produces antinociception. These data indicate that neurons located in the A5 nucleus may be the origin of this NA projection to the NRM. The elevation in tail-flick latency observed following A5 lesions was significantly attenuated by the intrathecal injection of either the NA antagonist phentolamine or the serotonergic antagonist methysergide. However, the elevation in hot-plate latency was not significantly altered by these monoaminergic antagonists. Similarly, previous studies have shown that the elevation in tail-flick, but not hot-plate latency, produced by the microinjection of NA antagonists in the NRM is attenuated by the intrathecal injection of either phentolamine or methysergide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influences of locus ceruleus, raphe dorsalis, and periaqueductal gray matter on somatosensory-recipient thalamic nuclei

Spontaneous and evoked discharge of neurons in the nucleus ventralis posterolateralis (VPL) and spontaneous discharge of neurons in the posterior group and nucleus lateralis posterior (LP) were conditioned by brief trains of stimuli to the locus ceruleus (LC), raphe dorsalis (RD), and periaqueductal gray matter (PAG) in cats anesthetized with pentobarbital or ketamine. Stimulation of LC and RD was without effect on VPL neurons, but induced a long-latency, long-lasting inhibition of LP neurons. Stimulation of the PAG induced marked inhibition of the firing of neurons in all three thalamic nuclei. No differences were found between cats anesthetized with ketamine or pentobarbital.     

GABAergic modulation of nociceptive threshold: effects of THIP and bicuculline microinjected in the ventral medulla of the rat

Neurons of the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (NGCp) have been implicated in the regulation of nociceptive threshold and production of antinociception. Previous studies have shown that the activity of these neurons is modulated by noradrenergic, cholinergic and serotonergic afferents. The present study examined whether these neurons are additionally subject to regulation by a GABAergic input. Microinjection of the GABA_A receptor agonist 4 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP; 0.3 or 1.0 μg) in the NRM or NGCp significantly decreased tail flick latency (TFL) and increased responsiveness to noxious pinch. Hot plate latency (HPL) was not affected by microinjection of 0.3 μg THIP. Although HPL was increased after microinjection of 1.0 μg THIP, this effect may reflect motoric disturbances. In contrast to the hyperalgesia produced by THIP, microinjection of the GABA_A receptor antagonist bicuculline methiodide (0.04 or 0.1 μg) produced a small, but significant increase in TFL. Responsiveness to noxious pinch and HPL were not affected by either dose. These findings indicate that neurons of the NRM or NGCp involved in the regulation of nociceptive threshold are subject to an inhibitory GABAergic input mediated by a GABA_A receptor. However, in contrast to previously described inhibitory inputs, the GABAergic influence does not appear to be tonically active to a substantial extent in the unanesthetized rat.     

Neuronal activity of the zona incerta in Parkinson's disease patients

The objective of this study was to describe the firing characteristics of the zona incerta (ZI) in Parkinson's disease patients. The ZI constitutes a band of gray matter lying dorsal to the subthalamic nucleus, whose firing properties have not been well defined in humans yet. ZI proved to become hyperactive in 6‐OHDA–lesioned rats as compared to normal rats, and regarding these noticeable changes in the discharge patterns it was suggested that ZI could be a putative target for the surgical treatment of Parkinson's disease. Twelve patients who underwent microrecording‐guided subthalamic surgery consented to the study. Neurons from different tracts were classified as belonging to the ZI according to their firing features, background extracellular activity, anatomical mapping of trajectories, and atlas confirmation. Fifty‐nine neurons were classified as belonging to ZI. The mean firing rate proved to be 29.5 Hz, with a broad dispersion band, even covering subthalamic nucleus (STN) frequency ranges. Pattern analysis showed heterogeneous neuronal signals ranging from tonic to burst and paused neurons. A decrease in extracellular background activity in the defined ZI was also observed. Five of the recorded neurons showed rhythmical spike trains with oscillations of 8 to 14 Hz, and two units were found to discharge trains at 4 Hz. None of the recorded ZI neurons responded to proprioceptive maneuvers. ZI presented firing activities with a broad spectrum in terms of frequency and tonicity. It is differentiated from STN recordings in Parkinson's disease patients mainly because of absent proprioceptive‐related units and diminished extracellular background activity. © 2006 Movement Disorder Society     

Evidence for pain modulation by pre- and postsynaptic noradrenergic receptors in the medulla oblongata

Activation of neurons in nucleus raphe magnus (NRM) produces hypoalgesia which most likely results from inhibition of spinal cord pain transmission pathways. Previous reports from this laboratory suggest that noradrenergic (NA) neurons modulate the activity of NRM neurons. More specifically, NA projections to NRM neurons appear to be inhibitory since iontophoretically applied norepinephrine (NE) inhibits the activity of NRM neurons. Furthermore, blockade of NA receptors in the NRM by the microinjection of alpha-adrenergic antagonists produces potent analgesia. Thus, the NA input to the NRM appears to increase pain sensitivity by tonically inhibiting NRM neurons. Pharmacological and physiological studies have differentiated alpha-adrenergic receptors into alpha-1 and alpha-2 subtypes. The present study was designed to examine the nature of the alpha-adrenergic receptor subtypes in the NRM and their role in the modulation of pain sensitivity. The results of these experiments are consistent with the classical model of postsynaptic alpha-1 receptors and presynaptic alpha-2 receptors which modulate NE release. Both the alpha-1 antagonist, prazosin, and the alpha-2 agonist, clonidine, produced an increase in nociceptive threshold. Conversely, both the alpha-1 agonist, phenylephrine, and the alpha-2 antagonist, yohimbine, produced a decrease in nociceptive threshold. Thus, in the region of the NRM, both presynaptic alpha-2 and postsynaptic alpha-1 noradrenergic receptors may be involved in the modulation of nociception.     

Long-lasting effects of feline amygdala kindling on monoamines, seizures and sleep

This report describes the relationship between monoamines, sleep and seizures before and 1-month after amygdala kindling in young cats (<1 year old; n=8; six female and two male). Concentrations (fmoles of norepinephrine or NE, dopamine or DA and serotonin or 5-HT) were quantified in consecutive, 5-min microdialysis samples (2 microl/min infusion rate) from amygdala and locus ceruleus complex (LC) during four, 6-8-h polygraphic recordings before (n=2) and 1 month post-kindling (n=2); 5-min recording epochs were temporally adjusted to correspond to dialysate samples and differentiated according to dominant sleep or waking state (lasting > or =80% of 5-min epoch) and degree of spontaneous seizure activity (number and duration of focal versus generalized spikes and spike trains and behavioral seizure correlates). Post-kindling records in each cat were divided into two groups (n=1 record each) based on higher or lower spontaneous EEG and behavioral seizure activity and compared to pre-kindling records. We found: (1) before and after kindling, NE and 5-HT but not DA concentrations were significantly lower in sleep than waking at both sites; (2) after kindling, each cat showed cyclic patterns, as follows: (a) higher NE, 5-HT and DA concentrations accompanied increased seizure activity with delayed sleep onset latency and increased sleep fragmentation (reduced sleep state percentages, number of epochs and/or epoch duration) in one recording versus (b) lower monoaminergic concentrations accompanied reduced seizure activity, rapid sleep onset and reduced sleep disruption in the other recording. The alternating, post-kindling pattern suggested "rebound" effects which could explain some controversies in the literature about chronic effects of kindling on monoamines and sleep-waking state patterns.     

The effect of modification of 5-hydroxytryptamine function in nucleus raphe magnus on nociceptive threshold

Thresholds to noxious heat stimulation were increased following microinjection of zimelidine, an inhibitor of 5-hydroxytryptamine (5-HT) re-uptake, into the nucleus raphe magnus (NRM) of rats. Pretreatment with intraperitoneally given cinanserin reduced this effect but pretreatment with intraperitoneally given phenoxybenzamine did not. Fenfluramine, which causes the release of 5-HT from synaptic terminals also elevated nociceptive thresholds following microinjection into NRM. Subanalgesic doses of morphine or zimelidine elevated nociceptive thresholds when microinjected together into NRM. The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM. Cinanserin alone had no effect when microinjected into NRM. These findings suggest that inhibition of the re-uptake of 5-HT in NRM can elevate nociceptive thresholds and that there may be an interaction between the effects of morphine and 5-HT in NRM.     

Inhibition of spinal nociceptive transmission from the midbrain, pons and medulla in the rat: activation of descending inhibition by morphine, glutamate and electrical stimulation

It is generally believed that morphine activates a descending system(s) of inhibition, an effect contributing significantly to the analgesia produced. There has arisen, however, considerable controversy on this point. To address whether morphine inhibits spinal nociceptive transmission when given into the brainstem, the effects of focal electrical stimulation and monosodium S-glutamate (Glu) given in the periaqueductal gray (PAG), the locus coeruleus/subcoeruleus (LC/SC) and/or the nucleus raphe magnus (NRM) on spinal unit responses to noxious heating (50 °C) of the skin were examined and compared with effects produced by morphine (Mor). Focal electrical stimulation in 46 sites in the midbrain, dorsolateral pons and ventromedial medulla reliably inhibited unit responses to noxious heating of the skin (mean 34% of control). Microinjections of Glu (50 nmol, 0.5 μl) were made into 17 sites in the midbrain, 10 sites in the LC/SC and 11 sites in the NRM, inhibiting unit responses to a mean 57% at 22 of the 38 sites of microinjection. Mor (10–20 μg, 0.5 μl) was microinjected into 15 sites in the midbrain, 13 sites in the LC/SC and 11 sites in the NRM, inhibiting unit responses to heat to 63% of control at 24 sites of microinjection. The effects of morphine were shown to be receptor specific by antagonism with naloxone administered either intravenously or into the brainstem at the same site of microinjection as morphine. In 31 sites in the midbrain, dorsolateral pons and ventromedial medulla, microinjections of both Mor and Glu into the same sites attenuated unit responses to heating of the skin to a mean 77% and 71% of control, respectively. The results support the hypothesis that Mor acts supraspinally to modulate spinal nociceptive transmission by activating an endogenous descending inhibitory system(s). Focal electrical stimulation, glutamate and morphine modulated spinal nociceptive transmission by activation of descending inhibitory systems whose cell bodies of origin are in the PAG, the LC/SC or the NRM.     

Changes in background activity of periaqueductal gray neurons through application of serotonin or inhibition of its synthesis]

Application of serotonin (ST, 1.10(-4) M to periaqueductal grey neurons influenced background activity (BA) only in the third group of cells. In 45.5% of them ST evoked depression of BA. Through application of ST remarkable potentiation of BA inhibition evoked by locus coeruleus (LC), substantia nigra (SN) stimulation was found, but inhibitory affects of nucleus raphe magnus (NRM) were less intensive. After intraperitoneal injection of p-chlorophenylalanine the efficiency of NRM stimulation became lower, but influences of LC and SN on BA increased. The mechanisms of serotoninergic effects on BA of periaqueductal grey neurons are discussed.     

Stimulation-produced spinal inhibition from the midbrain in the rat is mediated by an excitatory amino acid neurotransmitter in the medial medulla

It has been previously established that a bulbar relay plays an important role in descending inhibition of spinal dorsal horn nociceptive neurons and nociceptive reflexes produced by stimulation in the midbrain periaqueductal gray (PAG). In the present study, selected receptor antagonists were microinjected into the medial medullary nucleus raphe magnus (NRM) to determine whether descending inhibition of the tail flick (TF) reflex in the rat produced by focal electrical stimulation in the midbrain PAG was mediated by serotonin, opioid, or glutamate receptors on bulbospinal neurons in the NRM. It was determined in initial experiments that the serotonin receptor antagonist methysergide, the opioid receptor antagonist naloxone, the local anesthetic lidocaine, and the glutamate receptor antagonists gamma-D-glutamylglycine (DGG) and DL-2-amino-5-phosphonovalerate (APV) microinjected into the medulla all significantly increased the threshold of focal electrical stimulation in the medulla required to inhibit the TF reflex. The antinociceptive efficacy of agonists at opioid, serotonin, and glutamate receptors was also tested in other experiments. The microinjection of morphine (2.5-10 micrograms) into the NRM increased significantly TF latencies in a dose-dependent manner in rats in the awake or lightly anesthetized state; morphine was more potent in awake rats. Inhibition of the TF reflex produced by the microinjection of morphine was reversed by a subsequent microinjection of naloxone into the same site in the medulla. The microinjection of serotonin (5 and 10 micrograms), however, did not affect the latency of the TF reflex in either awake or lightly anesthetized rats. Glutamate (100 microM, 0.5 microliter) microinjected into the rostral ventral medulla produced an inhibition of the TF reflex of short duration that could be blocked or attenuated significantly by the glutamate receptor antagonists DGG or APV microinjected into the same site. In subsequent experiments, a nonspecific functional block was introduced adjacent to the NRM bilaterally in the medullary reticular formations (MRFs) by the microinjection of the local anesthetic lidocaine; receptor antagonists were then microinjected into the NRM and their effect on the threshold of focal electrical stimulation in the PAG to inhibit the TF reflex determined. No increase was seen in stimulation thresholds in the PAG following the microinjection of either methysergide or naloxone into the NRM. Following the microinjection of lidocaine, DGG or APV into the NRM, the stimulation threshold in the PAG for inhibition of the TF reflex was increased significantly.(ABSTRACT TRUNCATED AT 400 WORDS)     

In vivo intracellular characteristics of inferior colliculus neurons in guinea pigs

Intracellular in vivo recordings of physiologically identified inferior colliculus central nucleus (ICc) auditory neurons (n=71) were carried out in anesthetized guinea pigs. The neuronal membrane characteristics are described showing mainly quantitative differences with a previous report [Nelson, P.G. and Erulkar, S.D., J. Neurophysiol., 26 (1963) 908–923]. The spontaneous spike activity was consistent with the discharge pattern of most extracellularly recorded units. The action potentials showed different spike durations, short and long, and some of them exhibited hyperpolarizing post-potentials. There were also differences in firing rate. The ICc neurons exhibited irregular activity producing spike trains as well as long silent periods (without spikes). Intracellular current injection revealed membrane potential adaptation and shifts that outlasted the electrical stimuli by 20–30 ms. Both evoked synaptic potentials and the spike activity in response to click and tone-burst stimulation were analyzed. Depolarizing-hyperpolarizing synaptic potentials were found in response to contralateral and binaural sound stimulation that far outlasted the stimulus (up to 90 ms). When ipsilaterally stimulated, inhibitory responses and no-responses were also recorded. Although few cells were studied, a similar phenomenon was observed using tone-burst stimulation; moreover, a good correlation was obtained between membrane potential shifts and the triggered spikes (input–output relationship). These in vivo results demonstrate the synaptic activity underlying many of the extracellularly recorded discharge patterns. The data are consistent with the known multi-synaptic ascending pathway by which signals arrive at the ICc as well as the descending corticofugal input that may contribute to the generation of long duration post-synaptic potentials.     

Antinociception induced by local injections of carbachol into the nucleus raphe magnus in rats: Alteration by intrathecal injection of monoaminergic antagonists

Electrical stimulation of neurons located in the nucleus raphe magnus (NRM) produces antinociception which appears to result from inhibition of spinothalamic tract neurons located in the spinal cord dorsal horn. Iontophoretic application of acetylcholine also activates NRM neurons and microinjection of cholinergic agonists such as carbachol into the NRM produces a profound, long-lasting antinociception. Since the antinociception induced by electrical stimulation of NRM neurons is mediated, at least in part, by bulbospinal serotonergic and noradrenergic neurons, the role of these monoaminergic neurons in mediating the antinociception induced by microinjecting carbachol in the NRM was examined in the present study. To this end, various antagonists of serotonin and norepinephrine were injected into the spinal cord subarachnoid space following the induction of antinociception by the local injection of carbachol into the NRM. The serotonergic antagonist methysergide had no effect on carbachol-induced antinociception. However, the alpha 2-noradrenergic antagonist yohimbine attenuated, while the alpha 1-noradrenergic antagonists prazosin and WB4101 increased the effects of carbachol. The non-selective noradrenergic antagonist phentolamine also attenuated the effects of carbachol. These results lead to the suggestion that the antinociception induced by the local injection of carbachol into the NRM is mediated by selective activation of bulbospinal noradrenergic neurons. Furthermore, the antinociception resulting from the activation of these descending noradrenergic neurons appears to be mediated by alpha 2-noradrenergic receptors located in the spinal cord dorsal horn. Finally, the local injection of carbachol into the NRM also appears to activate another population of noradrenergic neurons which produces hyperalgesia mediated by alpha 1-noradrenergic receptors.     

Comparison of the effects of ventral medullary lesions on systemic and microinjection morphine analgesia

The effects of electrolytic lesions of the nucleus raphe magnus (NRM), nucleus reticularis paragigantocellularis (PGC) and nucleus raphe alatus (NRA) on analgesia elicited in the rat from systemic morphine and morphine microinjection into the periaqueductal gray (PAG) were evaluated using the tail flick test. No consistent change in baseline pain sensitivity was observed following lesions of the NRM, PGC or NRA. To determine the effect of ventral medullary lesions on systemic porphine analgesia, pain sensitivity was assessed prior to and 40 min after 6 mg/kg morphine administration (i.p.) at 2 days preceding lesioning and 5, 12 and 19 days post-lesion. NRM and PGC lesions produced only slight reductions in analgesia at 5 days after surgery. It was observed that large NRM, large PGC, and NRA lesions significantly attenuated analgesia evaluated at 12 days post-lesion. Smaller lesions confined within the NRM or PGC were reliably less effective than the larger lesions in reducing analgesia. In a subsequent study, 5 μg morphine in 0.5 μl saline was microinjected into the ventral PAG at the level of the dorsal raphe. Identical testing procedures were used and the analgesia was assessed at 2 days before lesioning and 5 and 12 days post-lesion. In contrast to the previous study, large NRM lesions abolished analgesia as early as 5 days following lesioning. Small NRM lesions were less effective and PGC lesions were generally ineffective in attenuating analgesia induced by morphine microinjection. We conclude that the NRA may act as a functional unit in the mediation of systemic morphine analgesia. In contrast, analgesia elicited from intracerebral (PAG) morphine microinjection is mediated via the NRM.     

Role of Barrington’s nucleus in the activation of rat locus coeruleus neurons by colonic distension

The locus coeruleus (LC)-noradrenergic system, which has been implicated in arousal and attention, is activated by visceral stimuli such as colon and bladder distension. Neurons of Barrington's nucleus (the pontine micturition center) have been identified which project to both the LC and preganglionic column of the lumbosacral spinal cord. Thus, Barrington's nucleus is positioned to coordinate brain noradrenergic activity with pelvic visceral functions. The aim of this study was to determine whether LC activation by colonic distension was mediated by projections from Barrington's nucleus to the LC in the rat. Lesions of Barrington's nucleus were performed unilaterally by local injection of ibotenic acid (microg/microl, 90 nl) 10 days prior to recording: (i) ipsilateral spontaneous LC discharge rate; (ii) LC responses to colonic distension; and (iii) LC responses to sciatic nerve stimulation. In some rats LC activation by hypotensive challenge was also examined. Lesions of Barrington's nucleus significantly reduced LC activation by colon distension from a magnitude of 26.6+/-6% increase in discharge rate (n=8) to 6.9+/-3% (n=6), while having no effect on basal LC discharge rate. In contrast, LC responses to sciatic nerve stimulation were not altered in rats with lesions of Barrington's nucleus and LC neurons were still activated by hypotensive challenge. These results support the hypothesis that Barrington's nucleus selectively relays input from pelvic visceral afferents to the LC. This may serve as a limb in a circuit designed to coordinate central and peripheral responses to pelvic visceral stimuli.     

Locus coeruleus-induced inhibition of dorsal cochlear nucleus neurons in comparison with lateral vestibular nucleus neurons

The effects of conditioning stimulation of the locis coeruleus (LC) on the neuron activity of dorsal cochlear nucleus (DCN), which is rich in noradrenergic nerve terminals, were compared with those on the lateral vestibular nucleus (LVN), devoid of such terminals, to determine whether or not noradrenaline is responsible for the LC-induced inhibition. The conditioning stimuli applied to the LC had no effect on either the field potential or the spike generation of mono- and polysynaptic neurons in the LVN elicited by VIIIth cranial nerve stimulation. In contrast, the spike firing of the DCN neurons with VIIIth cranial nerve stimulation was significantly inhibited by LC conditioning stimulation. The inhibition of spike generation was mainly observed in the DCN neurons which fired spikes with a longer latency. The inhibition of DCN neurons by LC conditioning stimulation did not occur in the cats pretreated with reserpine; however, a rapid recovery of the inhibition was produced by intraventricular application of noradrenaline. These results are in good agreement with the histochemical findings and support our previous conclusion that noradrenaline acts as an inhibitory transmitter or modulator on the nuclei where noradrenergic nerve terminals derived from the LC are located. In addition, the vestibular input in the primary relay nucleus is apparently not regulated by noradrenaline originating in the LC.