Short-train Stimulation Research Articles

Continuous subcortical language mapping in awake glioma surgery.

Repetitive monopolar short-train stimulation (STS) delivered from a suction probe enables continuous mapping and distance assessment of corticospinal tracts during asleep glioma resection. In this study, we explored this stimulation technique in awake glioma surgery. Fourteen patients with glioma involving language-related tracts were prospectively included. Continuous (3-Hz) cathodal monopolar STS (five pulses, 250 Hz) was delivered via the tip of a suction probe throughout tumor resection while testing language performance. At 70 subcortical locations, surgery was paused to deliver STS in a steady suction probe position. Monopolar STS influence on language performance at different subcortical locations was separated into three groups. Group 1 represented locations where STS did not produce language disturbance. Groups 2 and 3 represented subcortical locations where STS produced language interference at different threshold intensities (≥7.5 and ≤5 mA, respectively). For validation, bipolar Penfield stimulation (PS; 60 Hz for 3 s) was used as a “gold standard” comparison method to detect close proximity to language-related tracts and classified as positive or negative regarding language interference. There was no language interference from STS in 28 locations (Group 1), and PS was negative for all sites. In Group 2 (STS threshold ≥ 7.5 mA; median, 10 mA), there was language interference at 18 locations, and PS (median, 4 mA) was positive in only one location. In Group 3 (STS threshold ≤ 5 mA; median, 5 mA), there was language interference at 24 locations, and positive PS (median 4 mA) was significantly (p < 0.01) more common (15 out of 24 locations) compared with Groups 1 and 2. Despite the continuous stimulation throughout tumor resection, there were no seizures in any of the patients. In five patients, temporary current spread to the facial nerve was observed. We conclude that continuous subcortical STS is feasibly also in awake glioma surgery and that no language interference from STS or interference at ≥7.5 mA seems to indicate safe distance to language tracts as judged by PS comparisons. STS language interference at STS ≤ 5 mA was not consistently confirmed by PS, which needs to be addressed.

Motor representation of rhythmic jaw movements in the amygdala of guinea pigs

ObjectiveThe areas of the amygdala contributing to rhythmic jaw movements and the movement patterns induced remain unknown. Therefore, the present study investigated the areas of the amygdala contributing to rhythmic jaw movements using repetitive electrical microstimulation techniques. DesignExperiments were performed on head-restrained guinea pigs under ketamine-xylazine anesthesia. EMG activities in the masseter and digastric muscles and jaw movements were recorded. Short- and long-train electrical microstimulations of the amygdala were performed and the patterns of jaw movements induced were analyzed quantitatively. ResultThe short-train stimulation induced short-latency EMG responses in the masseter and/or digastric muscles. The stimulation sites inducing short-latency EMG responses were distributed within the ventral part of the amygdala, which covered the medial, basal, and cortical nuclei. The long-train stimulation induced tonic jaw opening and two types of rhythmic jaw movements: those with or without lateral jaw shifts, which were characterized by a larger jaw gape and ipsilateral jaw excursion, respectively. Rhythmic jaw movements with lateral jaw shifts were characterized by overlapping masseter and digastric EMG activities. However, rhythmic patterns did not differ between the two types of rhythmic jaw movements. The stimulation sites that induced rhythmic jaw movements were more localized to the cortical nucleus. ConclusionsThe present results suggest that the ventral part of the amygdala is involved in the induction of rhythmic jaw movements in guinea pigs. The putative roles of the limbic system in the genesis of functional (e.g., chewing) and non-functional (e.g., bruxism) rhythmic oromotor movements warrant further study.

Hyperexcitability in synaptic and firing activities of spinal motoneurons in an adult mouse model of amyotrophic lateral sclerosis

Hyperexcitability is hypothesized to contribute to the degeneration of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS). Studies, thus far, have not linked hyperexcitability to the intrinsic properties of MNs in the adult ALS mouse model with the G93A-mutated SOD1 protein (mSOD1G93A). In this study, we obtained two types of measurements: ventral root recordings to assess motor output and intracellular recordings to assess synaptic properties of individual MNs. All studies were carried out in an in vitro preparation of the sacral spinal cords of mSOD1G93A mice and their non-transgenic (NT) littermates, both in the age range of 50–90days. Ventral root recordings revealed that maximum compound action potentials (coAPs) evoked by a short-train stimulation of corresponding dorsal roots were similar between the two types of mice. Although the progressive depression of coAPs was present during the train stimulation in all recordings, the coAP depression in mSOD1G93A mice was to a lesser extent, which suggests an increased firing tendency in mSOD1G93A MNs. Intracellular recordings showed no changes in fast excitatory postsynaptic potentials (EPSPs) in mSOD1G93A MNs. However, recording did show that oscillating EPSPs (oEPSPs) were induced by poly-EPSPs at a higher frequency and by less-intense electrical stimulation in mSOD1G93A MNs. These oEPSPs were dependent upon the activities of spinal network and N-methyl-d-aspartate receptors (NMDARs), and were subjected to riluzole modulation. Taken together, these findings revealed abnormal electrophysiology in mSOD1G93A MNs that could underlie ALS excitotoxicity.

A review of monopolar motor mapping and a comprehensive guide to continuous dynamic motor mapping for resection of motor eloquent brain tumors

Monopolar mapping of motor function differs from the most commonly used method of intraoperative mapping, i.e. bipolar direct electrical stimulation at 50–60Hz (Penfield technique mapping). Most importantly, the monopolar probe emits a radial, homogenous electrical field different to the more focused inter-tip bipolar electrical field. Most users combine monopolar stimulation with the short train technique, also called high frequency stimulation, or train-of-five techniques. It consists of trains of four to nine monopolar rectangular electrical pulses of 200–500μs pulse length with an inter stimulus interval of 2–4msec. High frequency short train stimulation triggers a time-locked motor-evoked potential response, which has a defined latency and an easily quantifiable amplitude. In this way, motor thresholds might be used to evaluate a current-to-distance relation. The homogeneous electrical field and the current-to-distance approximation provide the surgeon with an estimate of the remaining distance to the corticospinal tract, enabling the surgeon to adjust the speed of resection as the corticospinal tract is approached. Furthermore, this stimulation paradigm is associated with a lower incidence of intraoperative seizures, allowing continuous stimulation. Hence, monopolar mapping is increasingly used as part of a strategy of continuous dynamic mapping: ergonomically integrated into the surgeon's tools, the monopolar probe reliably provides continuous/uninterrupted feedback on motor function. As part of this strategy, motor mapping is not any longer a time consuming interruption of resection but rather a radar-like, real-time information system on the spatial relationship of the current resection site to eloquent motor structures.

Jaw movement-related primary somatosensory cortical area in the rat

It has anatomically been revealed that the rostral part of the rat primary somatosensory cortex (S1) directly projects to the dorsal part of the trigeminal oral subnucleus (dorVo) and the dorsal part of juxtatrigeminal region (dorVjuxt), and that the dorVo and dorVjuxt contain premotoneurons projecting directly to the jaw-opening or jaw-closing motoneurons in the trigeminal motor nucleus (Vmo). However, little is known about how the rostral S1 regulates jaw movements in relation to its corticofugal projections. To address this issue, we performed intracortical microstimulation of the rat rostral S1 by monitoring jaw movements and electromyographic (EMG) activities. We for the first time found that low-frequency long-train stimulation of the rostral S1 induced single sustained opening of the jaw with elevated EMG activities of the anterior digastric muscles (jaw-opener). The effective sites for the low-frequency long-train stimulation overlapped the S1 sites where traditional high-frequency short-train stimulation was effective to induce single twitch-like jaw movement. We also found that the effective sites for the two kinds of train stimuli were included in the rostral S1 area, which has previously been identified to send direct projections to the dorVo or the dorVjuxt. Specifically, the most effective stimulation sites for the two kinds of train stimuli were located in the rostralmost part of S1 which has been reported to emanate strong direct projections to the dorVjuxt but less to the dorVo. Therefore, the present study suggests that the rat rostral S1, especially its rostralmost part, plays an important role in controlling jaw movements by activation of direct descending projections from the rostral S1 to the trigeminal premotoneuron pools, especially to the dorVjuxt.

5. Neurophysiological monitoring in awake craniotomy

Introduction Awake craniotomy with neurophysiological monitoring is often performed in patients with brain tumours in close proximity to functional brain areas (speech, motor, internal capsule). We describe our experience in 35 patients. Materials and methods 35 patients with brain tumours adjacent to eloquent areas were operated on during a time frame of five years. Among these, 23 patients had oligodendroglioma grade 2, 4 patients had astrocytoma grade 2, 1 patient had oligodendroglioma grade 3, 2 patients had oligoastrocytoma grade 2, 4 patients had glioblastoma and 1 patient had Multiple Sclerosis. 14 brain tumours were located as follows: left frontal, 11 right frontal, 2 left temporal, 2 left parietal, 4 right frontotemporal (insula), 2 left frontotemporal (insula). The sleep-wake-sleep procedure was used for most of the patients. Direct cortical stimulation (DCS) was used to map the motor cortex and language areas. Median nerve SSEP was used to localize the central sulcus. Subcortical electrical stimulation was used to localize the motor tract during tumour resection. EEG was recorded to monitor seizure discharges. Monitoring of motor function was done by manual testing of motor performance and DCS. Monitoring of language function was performed by talking to the patients, counting and picture naming. Results 21 patients had transient neurological deficitswhich full recovered. 1 patient had permament neurological deficit. 2 patients were converted from awake to asleep craniotomy due to acute psychological distress and seizure during surgery. Neurophysiological monitoring was helpful and feasible in all cases, helping the surgeon to detect functional brain areas thus enabling him to resect the brain tumour with high security. Seizure during DCS occurred in one patient. Conclusion Neurophysiological monitoring during awake craniotomy is feasible and reproducible. There were no major side effects during monitoring. After introducing short train stimulation for language area mapping no seizures occurred.

Discontinuous Long-Train Stimulation in the Anterior Striatum in Monkeys Induces Abnormal Behavioral States

The striatum has been identified as a new target for therapeutic deep brain stimulation in the treatment of neurological and psychiatric disorders. The nonhuman primate model offers opportunities for detailed mapping of the behavioral effects of stimulation within the striatum. We recently showed that dysfunction in the dorsal and ventral striatum was able to produce a specific pattern of abnormal movements and behavioral states. In the present study, electrical stimulation of monkey striatum evoked abnormal movements and behavioral states depending not only on the location of stimulation sites but also on the parameters of stimulation. Abnormal movements were induced by stimulation of sites in the anterior associative and posterior sensorimotor striatum. Short-train stimulation evoked myoclonic-like movements and long-train stimulation produced sustained dystonic-like and complex abnormal movements. Long-train stimulation of the anterior part of the striatum, corresponding to the associative-limbic territory, induced 3 abnormal behavioral states--hyperactivity, hypoactivity, and stereotyped behaviors. Short-train stimulation was less effective in producing these effects. No significant effects were observed with the continuous mode of stimulation. Our results show that discontinuous long-train stimulation of the anterior associative and limbic parts of the striatum is the most effective mode of stimulation to produce these behavioral states.

Differential responses of sympathetic premotor neurons in the rostral ventrolateral medulla to stimulation of the dorsomedial hypothalamus in rabbits

Electrical stimulation of the posterior dorsomedial hypothalamus (DMH) elicits a defense response, including vasodilation in the skeletal muscles and vasoconstriction in the viscera. To examine whether sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) participate in these differential vascular responses, RVLM neuron activity, renal sympathetic nerve activity (RSNA), renal vessel conductance (RVC), skeletal muscular vessel conductance (MVC), arterial pressure (AP), and heart rate (HR) were simultaneously measured in urethane-anesthetized, vagotomized, and immobilized rabbits. Electrical stimulation of the DMH increased RSNA, MVC, AP, and HR but decreased RVC. The RVLM neurons were classified into three groups according to their responses to tetanic (10 s) stimulation of the DMH. Twenty neurons (Type I) were excited, 17 (Type II) were inhibited, and 2 (Type III) did not respond. To the short-train (100 ms) stimulation, all of the Type I neurons showed excitation; in contrast, 12 Type II neurons showed biphasic response that was early excitation followed by inhibition. The remainder showed only inhibition. Type III neurons also did not respond to the short-train stimulation. These results indicated that regional differences in responses of sympathetic nerves in the defense response are supported by functional differentiation of sympathetic premotor neurons in the RVLM.

Successful localization of the Broca area with short-train pulses instead of ‘Penfield’ stimulation

Direct electrical stimulation of functional cortical areas is a standard procedure in epilepsy and glioma surgery. Many previous studies support that stimulation of the motor cortex with short-train pulses is a less epileptogenic alternative to the 50–60 Hz ‘Penfield’ technique. However, whether the short-train stimulation is useful also in mapping of speech areas is unclear. In this case report we present a patient with oligodendroglioma near the Broca area. Extraoperative electrical stimulation via a subdural grid electrode was primarily performed to locate the speech area. The cortex was stimulated with short-train pulses (5 pulses, 0.5 pulse duration and 3 ms interpulse interval) in addition to 1–3 s 50 Hz stimulation. The patient had speech arrest from both types of stimulation techniques during a naming task. It was however critical that the short (14.5 ms) train stimulation was synchronized with the presentation of the naming objects. If not, there was no speech arrest. Despite this possible pitfall, this case has encouraged us to further try short-train stimulation in attempts to reduce stimulus-triggered seizures during mapping of eloquent areas.

GABAergic Interneurons Facilitate Mossy Fiber Excitability in the Developing Hippocampus

Profound activity-dependent synaptic facilitation at hippocampal mossy fiber synapses is a unique and functionally important property. Although presynaptic ionotropic receptors, such as kainate receptors, contribute partially to the facilitation in the hippocampus, the precise mechanisms of presynaptic regulation by endogenous neurotransmitters remain unclear. In this study, we report that axonal GABA(A) receptors on mossy fibers are involved in the activity-dependent facilitation during development. In immature mouse hippocampal slices, short-train stimulation (five pulses at 25 Hz) caused frequency-dependent facilitation of not only postsynaptic responses but also presynaptic fiber volleys that represent presynaptic activities. This fiber volley facilitation was inhibited by selective GABA(A) receptor antagonists, or by enkephalin that selectively suppresses excitability of interneurons. Furthermore, we directly demonstrated that this facilitation resulted from depolarization of mossy fibers in imaging experiments using a voltage-sensitive dye. This increased mossy fiber excitability caused by depolarizing action of GABA gradually decreased with development and eventually disappeared at around postnatal day 30. These results suggested that GABA released from interneurons acted on axonal GABA(A) receptors on mossy fibers and contributed at least partially to the activity- and age-dependent facilitation in the hippocampus.

Comparison between short train, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS) of the human motor cortex

Objective To compare motor evoked potentials (MEPs) elicited by short train, monophasic, repetitive transcranial magnetic stimulations (rTMS) with those by short train, biphasic rTMS. Methods Subjects were 13 healthy volunteers. Surface electromyographic (EMG) responses were recorded from the right first dorsal interosseous muscle (FDI) in several different stimulation conditions. We gave both monophasic and biphasic rTMS over the motor cortex at a frequency of 0.5, 1, 2 or 3 Hz. To study excitability changes of the spinal cord, we also performed 3 Hz rTMS at the foramen magnum level [Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I. Magnetic stimulation of corticospinal pathways at the foramen magnum level in humans. Ann Neurol 1994;36:618–24]. We measured the size and latency of each of 20 MEPs recorded in the different stimulation conditions. Results 2 or 3 Hz stimulation with either monophasic or biphasic pulses evoked MEPs that gradually increased in amplitude with the later MEPs being significantly larger than the earlier ones. Monophasic rTMS showed much more facilitation than biphasic stimulation, particularly at 3 Hz. Stimulation at the foramen magnum level at 3 Hz elicited fairly constant MEPs. Conclusions The enhancement of cortical MEPs with no changes of responses to foramen magnum level stimulation suggests that the facilitation occurred at the motor cortex. We hypothesize that monophasic TMS has a stronger short-term effect during repetitive stimulation than biphasic TMS because monophasic pulses preferentially activate one population of neurons oriented in the same direction so that their effects readily summate. Biphasic pulses in contrast may activate several different populations of neurons (both facilitatory and inhibitory) so that summation of the effects is not so clear as with monophasic pulses. When single stimuli are applied, however, biphasic TMS is thought to be more powerful than monophasic TMS because the peak-to-peak amplitude of stimulus pulse is higher and its duration is longer when the same intensity of stimulation (the same amount of current is stored by the stimulator) is used. Significance This means that when using rTMS as a therapeutic tool or in research fields, the difference in waveforms of magnetic pulses (monophasic or biphasic) may affect the results.

Possible involvement of the facial nucleus in regulation of respiration in rats

The facial nucleus (FN) has been known as a motor nucleus to control the activity of the facial skeletal muscles by its efferent somatic motoneurons. Much less, however, is known about the non-motor control functions of its interneurons. The present study was designed to investigate if the interneurons of the FN participate in controlling rhythmic respiration in the sodium thiopental-anesthetized and vagotomized Sprague–Dawley rats with facial motoneurons retrogradely degenerated with techniques of electrical and chemical stimulation of the FN and extracellular recording of discharge of neurons in the FN. Single pulse stimulation (75–100 μA, 0.2 ms) of the FN during inspiration caused a transient restrain in phrenic discharge. Short train stimulation (75–100 μA, 0.2 ms, 100 Hz, 3–5 pulses) delivered during the early- or mid-term of inspiration augmented the inspiratory duration, but switched the inspiration off when delivered during the later stage of inspiration. Short train stimulation delivered during expiration prolonged the expiratory duration. Continuous stimulation could inhibit the inspiration. Microinjection of kainic acid into the FN caused an augmentation in inspiratory duration and amplitude and in expiratory duration. These data indicate that the interneurons of the FN might participate in the modulation of respiration. Different discharge patterns of interneurons in the FN, interestingly some respiratory related patterns, were observed, which provide a possible structural basis for the role of the FN in respiratory regulation.

SEROTONERGIC Pontomedullary Neurons Are Not Activated by Antinociceptive Stimulation in the Periaqueductal Gray

The antinociceptive and cardiovascular effects of midbrain periaqueductal gray (PAG) stimulation are mediated through a relay in the pontomedullary raphe magnus (RM) and adjacent nucleus reticularis magnocellularis (NRMC). To test whether the neurons important in mediating PAG-evoked effects are SEROTONERGIC, the responses of pontomedullary SEROTONERGIC-LIKE cells to PAG stimulation were tested. SEROTONERGIC-LIKE neurons (n = 21) were recorded extracellularly in halothane-anesthetized Sprague Dawley rats. Serotonergic-like neurons were distinguished by their slow and steady background discharge. Two neurons that were physiologically characterized as SEROTONERGIC-LIKE were intracellularly labeled and processed for serotonin immunoreactivity; both cells tested contained immunoreactive serotonin. Train stimulation of sites within the midbrain PAG, at intensities of </=50 microA, suppressed the tail withdrawal from noxious heat and evoked changes in blood pressure and heart rate. No SEROTONERGIC-LIKE cells were activated by single-pulse or short-train (two to five pulses) stimulation of the PAG at antinociceptive intensities. In most cases, SEROTONERGIC-LIKE cells were unaffected by long-train stimulation (5-6 sec) of the PAG, which produced antinociception and cardiovascular changes. In contrast, >50% of the cells in two nonserotonergic-like cell classes were activated at short latency by such PAG stimulation. In conclusion, monosynaptic excitation of SEROTONERGIC cells in RM/NRMC is unlikely to be necessary for the nociceptive and autonomic modulatory effects of PAG stimulation.

Reappraisal of the inspiratory effect of Bötzinger complex on phrenic nerve discharge

Experiments were done on 12 urethane-chloralose anaesthetized, vagotomized, paralysed and ventilated cats. The effects of electrical microstimulation at the augmenting expiratory neurons (Aug-e) of Bötzinger complex (Bot.c) were investigated. It was found that long train stimulation (100 Hz, 3–50 μA, 4–6 s) caused intensity-dependent inhibition of phrenic inspiratory discharge. The threshold for complete inhibition was 10 ± 2 μA (mean ± S.E.). The expiratory duration showed shortening at low intensity (<7 μA) and prolongation at higher intensity. Short train stimulation (10 μA, 50 ms) delivered in inspiratory phase produced a two-part transient inhibition of phrenic discharge. The latencies of the first- and second-part inhibition were 4.7 ± 0.16 ms and 95 ± 3 ms, respectively. Complete termination of inspiration could be produced by a short train delivered at late inspiration. The results suggest the importance of the Aug-e neurons of Bot.c in determining inspiratory amplitude and respiratory phase duration.

Development of cholinergic and inhibitory non-adrenergic non-cholinergic responses in the rat gastric funds.

1. Cholinergic contractions and inhibitory non-adrenergic non-cholinergic (NANC) relaxations were studied in longitudinal muscle strips of the gastric funds of 2, 4 and 8 week old rats. 2. Contractions induced by electrical stimulation of the cholinergic neurones and by administration of acetylcholine decreased during development. The potentiating effect of physostigmine was similar in the 3 age groups. 3. Short train stimulation in NANC conditions induced fast relaxations, which were more pronounced in 4 and 8 week than in 2 week old rats. These relaxations were almost completely inhibited by NG-nitro-L-arginine methyl ester (L-NAME) in the 3 age groups. The nitric oxide-induced relaxations did not change during development. 4. Sustained electrical stimulation in NANC conditions induced an initial relaxation, which was almost totally blocked by L-NAME, followed by an almost complete recovery of tone at lower frequencies of stimulation. At higher frequencies of stimulation, the recovery of tone was incomplete or absent. This sustained relaxation was only partially reduced by L-NAME and almost abolished by L-NAME plus alpha-chymotrypsin. The initial relaxations increased during development, while the sustained relaxations remained similar during this period. Vasoactive intestinal polypeptide-induced relaxations were also similar in the 3 age groups. 5. These results show that the sensitivity of the gastric fundus to acetylcholine decreases from 2 weeks to 8 weeks postnatally, while the importance of the nitrergic innervation increases during this period.

Stimulus-dependent, reciprocal up- and downregulation of glutamic acid decarboxylase and Ca2+/calmodulin-dependent protein kinase II gene expression in rat cerebral cortex.

Long-train tetanic stimulation of the cerebral cortex induces long-term changes in the excitability of cortical neurons, while short-train electrical stimulation does not. In the present study, we show that both forms of stimulation when applied to rat motor cortex for 4 h enhance c-fos expression, but only tetanic stimulation, when imposed upon short-train stimulation, modulates gene expression for 67-kDa glutamic acid decarboxylase (GAD) and alpha Ca2+/calmodulin-dependent protein kinase II (CaMKII alpha). Gene expression for beta Ca2+/calmodulin-dependent protein kinase II is not affected by either stimulation mode. GAD messenger RNA (mRNA) is increased from 1 h after the end of tetanization to the longest poststimulus survival time investigated (14 h). CaMKII alpha mRNA is decreased 1-3 h after the end of tetanization but thereafter returns to prestimulus levels. These results imply not only that mechanisms underlying neocortical plasticity are stimulus-dependent but also that they involve reciprocal changes in molecules regulating the balance of excitation and inhibition.

Ventrolateral orbital cortex and periaqueductal gray stimulation-induced effects on on- and off-cells in the rostral ventromedial medulla in the rat.

On- and off-cells of the rostral ventromedial medulla are thought to be involved in bulbospinal inhibition of ascending nociceptive information. Experiments were carried out in lightly anaesthetized rats to assess the effects of prefrontal cortex stimulation on the responses of neurons in the rostral ventromedial medulla. For comparison purposes, effects of periaqueductal gray stimulation were also investigated. Single unit activity was recorded in the rostral ventromedial medulla and on-, off- and neutral-cells were identified based on the tail nocifensor reflex to noxious heat. Short (0.1-1 s) and long (10-15 s) trains of bipolar electrical stimulation (100-300 Hz) were delivered to the ventrolateral orbital cortex of the rat forebrain and the periaqueductal gray. Short-train stimulation of the periaqueductal gray (including dorsolateral, ventrolateral and the dorsal raphé regions) excited 58% (25 of 43) of on-cells and 44% (seven of 16) of off-cells in the rostral ventromedial medulla. Long trains blocked the noxious stimulus-evoked pause of all seven off-cells tested and blocked the excitatory response of two, and enhanced one of three on-cells. Such stimulation also inhibited or abolished the tail-flick reflex at currents below 100 microA. Glutamate microinjections into the periaqueductal gray inhibited the noxious-evoked response of two off- and two on-cells and increased the tail-flick latency. Short-train stimulation of the ventrolateral orbital cortex (100-400 microA) excited eight of 25 on-cells and inhibited the ongoing activity of 10 of 14 off-cells. Long-train ventrolateral orbital cortex stimulation (5-15 s, 100-200 microA, 200-300 Hz) enhanced the noxious evoked responses of 10 of 11 on-cells, prolonged the noxious heat-evoked pause of all of four off-cells and decreased the tail-flick latency (pronociception). The results of this study support the proposed role of on- and off-cells in descending inhibition of nociception from the periaqueductal gray and implicate the ventrolateral orbital cortex in the control of this pathway.

Endogenous angiotensin within the rostral ventrolateral medulla facilitates the somatosympathetic reflex

To determine whether endogenous angiotensin modifies the synaptic excitation of sympatho-excitatory neurons in the rostral part of the ventrolateral medulla. Experiments were performed on anaesthetized rabbits with denervated arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate and renal sympathetic nerve activity were measured. The average sympatho-excitatory reflex response evoked by short-train stimulation of the sciatic nerve was measured before and at various times after micro-injection of the non-specific angiotensin receptor antagonist [Sar1,Thr8]-angiotensin II (80 pmol) into the contralateral rostral ventrolateral medulla. Because the central pathway mediating this somatosympathetic reflex includes a synapse within the contralateral (but not ipsilateral) rostral ventrolateral medulla, a change in the evoked response after blockade of angiotensin receptors in the contralateral rostral ventrolateral medulla indicates a role of these receptors in synaptic transmission within this region. As a control, the effects on this reflex of micro-injection of [Sar1,Thr8]-angiotensin II into the ipsilateral rostral ventrolateral medulla were also measured. After injection of [Sar1,Thr8]-angiotensin II into the contralateral rostral ventrolateral medulla, the evoked sympatho-excitatory reflex response was significantly reduced compared with the response before injection. In contrast, injection of [Sar1,Thr8]-angiotensin II into the ipsilateral rostral ventrolateral medulla had no significant effect on the evoked sympatho-excitatory reflex response, although contralateral and ipsilateral injections of [Sar1,Thr8]-angiotensin II had very similar effects on baseline arterial pressure and renal sympathetic nerve activity. The results indicate that, in the anaesthetized rabbit with denervated arterial and cardiopulmonary baroreceptors, endogenous angiotensin is tonically released within the rostral ventrolateral medulla and facilitates the synaptic excitation of sympatho-excitatory neurons reflexly evoked by stimulation of afferent fibres in the sciatic nerve.

Neuropharmacological mechanisms underlying rhythmical discharge in trigeminal interneurons during fictive mastication

1. We have examined the effects of iontophoretic application of antagonists to excitatory amino acid (EAA) receptors, as well as glycine and gamma-aminobutyric acid (GABA), on rhythmically active (RA) brain stem neurons during cortically induced masticatory activity (RMA) in the anesthetized guinea pig. Ten of these neurons were antidromically activated at latencies of 0.3-0.9 ms by stimulation of the trigeminal motor nucleus (MoV). 2. RA neurons were divided into closer and opener type according to the phase of activation during RMA. Iontophoretic application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a specific non-N-methyl-D-aspartate (NMDA) receptor antagonist, suppressed discharge of both closer and opener type RA neurons during RMA. In contrast, iontophoretic application of 3-((1)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a specific NMDA receptor antagonist, was not effective in suppressing discharge of most opener type RA neurons but did reduce activity of closer type RA neurons. 3. Spike discharge of most RA neurons was time locked to each cortical stimulus during RMA. Some of the RA neurons were activated at a short latency to short pulse train stimulation of the cortex in the absence of RMA. In most cases CNQX reduced such time-locked responses during RMA and greatly reduced discharge evoked by short pulse stimulation of the cortex in all cases. In contrast, CPP was not as effective in suppressing either the time-locked responses during RMA or the discharge evoked by short pulse train stimulation of the cortex. 4. D,L-Homocysteic acid (HCA) application produced low level maintained discharge in RA neurons before RMA induction. When RMA was evoked in combination with HCA, rhythmical burst discharges with distinct interburst periods during the opening phase of RMA were observed in most closer type RA neurons. In contrast, during RMA in combination with HCA application, opener type RA neurons showed burst discharges that were modulated during the RMA cycle but lacked distinct interburst periods during the closer phase of the cycle. 5. During application of strychnine (STR), a glycine antagonist, discharge of closer type RA neurons increased in the opener phase of RMA during continuous HCA application. In contrast, bicuculline methiodide (BIC), a GABA antagonist, did not increase unit discharge of closer type RA neurons in the opener phase of RMA. 6. It is concluded that closer type RA neurons receive, alternatively, EAA-mediated excitatory and glycine-mediated inhibitory masticatory synaptic drive signals during RMA.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of anesthetic on sympathetic responses evoked from cerebellar uvula in decerebrate cats.

The sympathetic mechanisms involved in the conversion of the tachycardia-pressor response evoked by electrical stimulation of the uvula (lobule IX of the posterior cerebellar cortex) in the unanesthetized decerebrate cat to a bradycardia-depressor response in the same, but anesthetized preparation, were investigated. Sympathoexcitation was produced in the inferior cardiac and renal sympathetic nerves in response to short train stimulation (2-5 pulses, 100-500 Hz) of the uvula in the unanesthetized decerebrate cat, and when paired stimuli (conditioning and test) were applied, the test-evoked potential in both nerves was similar to the response elicited by the conditioning stimulus. Anesthetic administered to these same animals caused the test response in both sympathetic nerves to be greatly decreased, yet the conditioning response was unchanged. The attenuation of the test response by the conditioning stimulus diminished during recovery from anesthesia. The recovery of the test response paralleled the time course of the return of the tachycardia-pressor effect evoked by long train stimulation of the uvula. It appears that anesthesia does not block the sympathoexcitatory response but acts to augment sympathoinhibitory processes associated with uvula stimulation; some possible mechanisms are discussed.