Repetitive Bursts Research Articles

Episodic Bursting Activity and Response to Excitatory Amino Acids in Acutely Dissociated Gonadotropin-Releasing Hormone Neurons Genetically Targeted with Green Fluorescent Protein

The gonadotropin-releasing hormone (GnRH) system, considered to be the final common pathway for the control of reproduction, has been difficult to study because of a lack of distinguishing characteristics and the scattered distribution of neurons. The development of a transgenic mouse in which the GnRH promoter drives expression of enhanced green fluorescent protein (EGFP) has provided the opportunity to perform electrophysiological studies of GnRH neurons. In this study, neurons were dissociated from brain slices prepared from prepubertal female GnRH-EGFP mice. Both current- and voltage-clamp recordings were obtained from acutely dissociated GnRH neurons identified on the basis of EGFP expression. Most isolated GnRH-EGFP neurons fired spontaneous action potentials (recorded in cell-attached or whole-cell mode) that typically consisted of brief bursts (2-20 Hz) separated by 1-10 sec. At more negative resting potentials, GnRH-EGFP neurons exhibited oscillations in membrane potential, which could lead to bursting episodes lasting from seconds to minutes. These bursting episodes were often separated by minutes of inactivity. Rapid application of glutamate or NMDA increased firing activity in all neurons and usually generated small inward currents (<15 pA), although larger currents were evoked in the remaining neurons. Both AMPA and NMDA receptors mediated the glutamate-evoked inward currents. These results suggest that isolated GnRH-EGFP neurons from juvenile mice can generate episodes of repetitive burst discharges that may underlie the pulsatile secretion of GnRH, and glutamatergic inputs may contribute to the activation of endogenous bursts.

Synaptic regulation of the slow Ca2+-activated K+ current in hippocampal CA1 pyramidal neurons: implication in epileptogenesis.

The slow Ca2+-activated K+ current (sI(AHP)) plays a critical role in regulating neuronal excitability, but its modulation during abnormal bursting activity, as in epilepsy, is unknown. Because synaptic transmission is enhanced during epilepsy, we investigated the synaptically mediated regulation of the sI(AHP) and its control of neuronal excitability during epileptiform activity induced by 4-aminopyridine (4AP) or 4AP+Mg2+-free treatment in rat hippocampal slices. We used electrophysiological and photometric Ca2+ techniques to analyze the sI(AHP) modifications that parallel epileptiform activity. Epileptiform activity was characterized by slow, repetitive, spontaneous depolarizations and action potential bursts and was associated with increased frequency and amplitude of spontaneous excitatory postsynaptic currents and a reduced sI(AHP.) The metabotropic glutamate receptor (mGluR) antagonist (S)-alpha-methyl-4-carboxyphenylglycine did not modify synaptic activity enhancement but did prevent sI(AHP) inhibition and epileptiform discharges. The mGluR-dependent regulation of the sI(AHP) was not caused by modulated intracellular Ca2+ signaling. Histamine, isoproterenol, and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid reduced the sI(AHP) but did not increase synaptic activity and failed to evoke epileptiform activity. We conclude that 4AP or 4AP+Mg-free-induced enhancement of synaptic activity reduced the sI(AHP) via activation of postsynaptic group I/II mGluRs. The increased excitability caused by the lack of negative feedback provided by the sI(AHP) contributes to epileptiform activity, which requires the cooperative action of increased synaptic activity.

Pc1 pearls revisited: Structured electromagnetic ion cyclotron waves on Polar satellite and on ground

We study an event of structured electromagnetic ion cyclotron (EMIC) waves observed by the Polar satellite in good conjunction with the Finnish ground stations on April 25, 1997. Polar observed two EMIC wave bands around the plasmapause. He+ band waves consisted of repetitive bursts which were observed on ground as a classical Pcl pearl band. H+ band waves occurred over a large latitude range of more than 5° invariant latitude and were observed on ground as a broad, diffuse Pc1 pearl band with several subbands. We found the same repetition period of ∼100 s for the Polar He+ band bursts and ground Pc1 pearls, in conflict with the bouncing wave packet (BWP) model. Comparing the burst structure of He+ band waves in Polar and on ground, we found a transit time of ∼45 s and an average group velocity of ∼500 km s−1. Within the BWP model this velocity would lead to a pearl repetition period of more than 250 s, in dramatic contradiction with the observed repetition period. Moreover, the bursts of the two Polar bands were roughly simultaneous with no significant dispersion, contrary to the expectation of the BWP model. These results clearly reject the classical BWP model, i.e., that Pc1 pearls are generated by one wave packet bouncing from one hemisphere to another. Instead, we find that EMIC waves were accompanied by long‐period ULF waves which had a period very close to the repetition period of the simultaneous EMIC bursts. Interestingly, plasma density showed simultaneous fluctuations with roughly the same period. As an alternative to the BWP model, we discuss models where the EMIC wave packet structure and ULF waves are connected. We note that the suggested relation of EMIC wave packets and ULF waves offers a new explanation to the well‐known preference of Pc1 pearls for the plasmapause. We have also estimated the full Poynting flux of EMIC waves for the first time, using the three components of electric and magnetic fields. The magnitude of the total Poynting flux of the He+ band waves was ∼20–25 μW m−2 and strongly directed downward away from the equator.

Rhythmic feet movements while falling asleep.

During the wake-sleep transition and sleep, diverse motor phenomena such as hypnagogic foot tremor may occur in the lower extremities. We investigated the relevance of this phenomenon in 375 consecutive subjects examined polysomnographically in a sleep disorders center. Rhythmic feet movements while falling asleep (RFM) were found in 28 subjects (7.5%). RFM occurred mostly as single, short series with a duration of between 10 and 15 seconds. They had a high night-to-night variability and were detected as rhythmic, oscillating movements of the whole foot or toes. Surface electromyographic (EMG) recordings displayed series of repetitive phasic bursts with a periodicity mostly between 1 and 2 per second. Single EMG burst duration varied between 300 and 700 msec. RFM at highest intensity occurred during presleep wakefulness, and usually persisted in sleep stages 1 and 2. RFM did not have a major sleep-disturbing effect in any of the affected subjects. Due to its high prevalence and the lack of a major sleep-disturbing effect, short series of RFM could be considered a quasiphysiological phenomenon. However, in more severe forms of RFM with evidence of a sleep-disturbing effect, RFM should be considered abnormal.

The effects of remifentanil on epileptiform discharges during intraoperative electrocorticography in patients undergoing epilepsy surgery.

High-dose i.v. opioids (e.g., alfentanil, 50 microg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra-short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES. After Institutional Review Board approval, 25 adult patients undergoing elective ECoG-guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane < or =0.1% (end-tidal) in 50% N2O, and i.v. fentanyl, 2 microg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 microg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one-sided sign test; p values < or =0.05 were considered statistically significant. When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain. During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half-life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG-guided ES.

Mode locking in a periodically forced integrate-and-fire-or-burst neuron model.

The minimal "integrate-and-fire-or-burst" (IFB) neuron model reproduces the salient features of experimentally observed thalamocortical relay neuron response properties, including the temporal tuning of both tonic spiking (i.e., conventional action potentials) and post-inhibitory rebound bursting mediated by the low-threshold Ca2+ current, I(T). In previous work focusing on experimental and IFB model responses to sinusoidal current injection, large regions of stimulus parameter space were observed for which the response was entrained to periodic applied current, resulting in repetitive burst, tonic, or mixed (i.e., burst followed by tonic) responses. Here we present an exact analysis of such mode-locking in the integrate-and-fire-or-burst model under the influence of arbitrary periodic forcing that includes sinusoidally driven responses as one case. In this analysis, the instabilities of mode-locked states are identified as both smooth bifurcations of an associated firing time map and nonsmooth bifurcations of the underlying discontinuous flow. The explicit construction of borders in parameter space that define the instabilities of mode-locked zones is used to build up the Arnol'd tongue structure for the model. The zones for mode-locking are shown to be in excellent agreement with numerical simulations and are used to explore the observed stimulus dependence of burst versus tonic response of the IFB neuron model.

Ionic mechanisms underlying burst firing of layer III sensorimotor cortical neurons of the cat: an in vitro slice study.

We examined the ionic mechanisms underlying burst firing in layer III neurons from cat sensorimotor cortex by intracellular recording in a brain slice. Regular spiking was observed in 77.4% of 137 neurons in response to constant intracellular current pulses of 0.5- to 1-s duration. The rest of the neurons showed burst firing. An initial burst followed by regular-spike firing was seen in 71.0% of 31 bursting neurons. The rest of the bursting neurons (n = 9) exhibited repetitive bursting. In the bursting neurons, spikes comprising the burst were triggered from the afterdepolarization (ADP) of the first spike of the burst. We examined the ionic mechanisms underlying the ADP by applying channel-blocking agents. The ADP was enhanced (rather than blocked) by Ca2+ channel blockade. This enhancement of the ADP by Ca2+ channel blockade was apparent even after blockade of the afterhyperpolarization by apamin or intracellular Ca2+ chelation by EGTA. The firing rate of the regular-spiking cells was increased by apamin, intracellular EGTA or Ca2+ channel blockers. In 17.9% of the neurons examined (n = 56), these agents switched the regular-spiking pattern into a bursting one. Burst firing could not be changed to regular spiking by these agents. Four neurons that responded with a single initial burst in control solution responded with repetitive bursting after application of these agents. We conclude that the main function of Ca2+ influx in layer III neurons is to activate Ca2+-dependent K+ conductance, which prevents or limits burst firing. At a time when spike amplitude was unchanged, the ADP was blocked and the burst firing changed to regular spiking by extracellularly applied tetrodotoxin (TTX) or intracellularly applied N-(2,6-dimethylphenylcarbamoylmethyl) triethyl ammonium bromide (QX314). We concluded that a TTX- and QX314-sensitive Na+ current underlies the ADP and therefore contributes to the burst firing of layer III neurons from the cat cortex.

Two distinct types of repetitive bursting activity mediated by NMDA in hypothalamic neurons in vitro.

Hypothalamic magnocellular dorsal nucleus neurons were recorded from adult guinea pig brain slices with the whole-cell patch-clamp technique to determine the effects of N-methyl-D-aspartate (NMDA) applied in the bath or by iontophoresis. In a majority of cells (59 of 77, 76.6%), rhythmic bursting discharges were evoked by specific activation of NMDA receptors when the membrane was more negative than -60 mV. This endogenous rhythmic activity was resistant to tetrodotoxin. It was suppressed by removal of extracellular Mg2+, indicating the involvement of the voltage-dependent block of the NMDA channel by Mg2+. Application of thapsigargin showed that rhythmic activity did not depend on the release of Ca2+ from reticulum stores. Blockers of Ca2+ conductances Ni2+ and nifedipine had no effects on the bursts. Their repolarization did not involve the activation of a strophantidin- or ouabain-sensitive pump, but partly depended on an apamine-sensitive Ca2+-dependent K+current. In a small subset of cells (9 of 69, 13%), specific activation of NMDA receptors induced another type of bursting activity which consisted of repetitive low-threshold spikes sustaining bursts of action potentials. Rhythmic low-threshold spikes subsisted in the presence of tetrodotoxin but were suppressed by Ni2+. Increasing the amount of NMDA brought about a switch from the rhythmic low-threshold spike burst firing to the rhythmic bursting activity observed for the majority of cells. The present data show for the first time that NMDA receptor activation can induce two independent rhythmic bursting behaviours in the same neuron, probably depending on the strength of the glutamatergic drive.

ACTIVE RECOVERY BETWEEN HIGH-INTENSITY EXERCISE BOUTS IMPROVES PERFORMANCE IN HOCKEY PLAYERS

Background Active recovery (AR) compared to passive recovery (PR) between high-intensity exercise bouts increases total work achieved and promotes lactate clearance in hockey players. Previous studies applied AR via submaximal exercise sessions to reduce post-event fatigue. However, no study to date has applied AR between repeated supramaximal exercise bouts. Preliminary Data 6 sedentary subjects (4 male, 2 female) and 5 athletic subjects (3 male, 2 female) were tested to examine the effect of AR vs PR between consecutive 30-second supramaximal exercise bouts. Total work (joules) was higher in the athletic group than in the sedentary group (2871 vs. 1029; p < .02). Additionally, the data demonstrate a significant treatment effect of AR vs. PR (2127 vs. 1046; p < .02) as well as a significant interaction effect (p < .02). Thus AR, between supramaximal exercise bouts improves overall performance in normal subjects and athletes. Hypothesis AR between repetitive bouts of supramaximal activity in ice hockey players will result in greater performance as defined by total work achieved, and lactate clearance. Methods 3 amateur hockey players (3 male, mean age 26 ± 3 years, mean weight 83.5 ± 11.2 kg, mean VO2 max 45 ± 2.8 ml/O2/min) were tested. Each subject underwent three days of testing. Day 1 consisted of a baseline 30-second Wingate Power Test (WPT) on a Monark 818-E ergometer and baseline VO2 max testing on a Sensormedics electronically braked ergometer. On days 2 and 3, subjects were required to perform consecutive WPTs with a randomly-assigned 4-minute recovery period (AR at 28% of peak power, or PR) in between, until a 30% reduction in power occurred. Capillary lactate was taken when subjects reached a 30% reduction in power and every 5 minutes for 30 minutes after testing was completed. Results Means for total work achieved (joules) were 8646 with AR and 7151 with R, a significant difference (p < .021). In addition, capillary lactate levels (mmol) at the time of a 30% power reduction were 12.5 with AR, as compared to 15.8 with PR (p < .02). Conclusion This study is the first to document the dramatic beneficial effect of AR in between high-intensity exercise bouts in hockey players. Since the prevailing standard of recovery in ice hockey is PR, these results have potentially important implications in the recovery period between exercise bouts during a hockey game. Despite a small initial sample size, there is a significant effect of AR on performance, and currently further study is underway. The data also suggests that AR may be extremely valuable in sports where repetitive short bursts of high-intensity activity are required or in sports where muscle lactate accumulation may hinder performance. Supported by ACSM Reebok Grant for Human Performance and Injury Prevention 2000.

Focal myoclonus and propriospinal propagation

Objective: To investigate the relationship between axial segmental myoclonus and propriospinal myoclonus. Methods: A patient with a 3-year history of axial jerks evoked by physical effort and unexpected somesthetic and auditory stimulations was investigated. Polygraphy with multiple-channel axial and limb EMG recording was performed with off-line analysis. Results: Spontaneous, somesthetic and acoustic evoked jerks always began in the left rectus abdominis muscle with a single or repetitive EMG burst that could spread to other rostral and caudal muscles without engagement of cranial nerve innervated muscles, consistent with propriospinal propagation. Spontaneous and evoked jerks could however also appear focally in abdominal muscles and remain localized without any diffusion to other muscle segments. Conclusion: Focal axial myoclonus and propriospinal myoclonus may coexist. Conceivably the same spinal generator responsible for a monomeric segmental myoclonus may, under conditions of heightened excitability, cause a multimeric propriospinally propagated muscular activation.

Dynamics of striate cortical activity in the alert macaque: I. Incidence and stimulus-dependence of gamma-band neuronal oscillations.

Using single and multiunit recordings in the striate cortex of alert macaque monkeys, we find that gamma-band (20-70 Hz) oscillations in neuronal firing are a prominent feature of V1 neuronal activity. The properties of this rhythmic activity are very similar to those previously observed in the cat. Gamma-band activity is strongly dependent on visual stimulation, largely absent during spontaneous activity and, under the conditions of our experiment, not time-locked to the vertical refresh of the computer monitor (80 Hz) used to present the stimuli. In our sample, 61% of multiunit activity (MUA) and 46% of single-unit activity (SUA) was significantly oscillatory, with mean frequencies of 48+/-9 and 42+/-13 Hz, respectively. Gamma-band activity was most likely to occur when cells were activated by their optimal stimuli, but still occurred, although less often and with lower amplitude, in response to nonoptimal stimuli. The frequency of gamma-band activity also reflected stimulus properties, with drifting gratings evoking higher-frequency oscillations than stationary gratings. As in the cat, the spike trains of single cells showing gamma-band oscillations often displayed a pattern of repetitive burst firing, with intraburst firing rates of 300-800 Hz. The overall similarity of rhythmic neuronal activity in the primary visual cortex of cats and monkeys suggests that the phenomenon is not species-specific. The stimulus-dependence of the rhythmic activity is consistent with a functional role in visual perception.

Whole-cell recordings from preoptic/hypothalamic slices reveal burst firing in gonadotropin-releasing hormone neurons identified with green fluorescent protein in transgenic mice.

Central control of reproduction is governed by a neuronal pulse generator that underlies the activity of hypothalamic neuroendocrine cells that secrete GnRH. Bursts and prolonged episodes of repetitive action potentials have been associated with hormone secretion in this and other neuroendocrine systems. To begin to investigate the cellular mechanisms responsible for the GnRH pulse generator, we used transgenic mice in which green fluorescent protein was genetically targeted to GnRH neurons. Whole-cell recordings were obtained from 21 GnRH neurons, visually identified in 200-microm preoptic/hypothalamic slices, to determine whether they exhibit high frequency bursts of action potentials and are electrically coupled at or near the somata. All GnRH neurons fired spontaneous action potentials, and in 15 of 21 GnRH neurons, the action potentials occurred in single bursts or episodes of repetitive bursts of high frequency spikes (9.77 +/- 0.87 Hz) lasting 3-120 sec. Extended periods of quiescence of up to 30 min preceded and followed these periods of repetitive firing. Examination of 92 GnRH neurons (including 32 neurons that were located near another green fluorescent protein-positive neuron) revealed evidence for coupling in only 1 pair of GnRH neurons. The evidence for minimal coupling between these neuroendocrine cells suggests that direct soma to soma transfer of information, through either cytoplasmic bridges or gap junctions, has a minor role in synchronization of GnRH neurons. The pattern of electrical activity observed in single GnRH neurons within slices is temporally consistent with observations of GnRH release and multiple unit electrophysiological correlates of LH release. Episodes of burst firing of individual GnRH neurons may represent a component of the GnRH pulse generator.

Mismatch negativity and behavioural discrimination in humans as a function of the magnitude of change in sound duration

This study investigated how duration changes are processed in the human brain as indexed by the mismatch negativity (MMN), a component of the auditory event-related potential (ERP) reflecting sensory memory. Subjects were presented with sequences of repetitive 100-ms white noise bursts interspersed by occasional duration deviants which were 1, 10, or 50 ms (decrements) or 110, 150, or 200 ms (increments) in duration. In a separate task, subjects were asked to detect deviants within the sequence via a button-press. MMN was elicited by both stimulus decrements and increments and increased in amplitude as a function of the amount of deviation from the standard duration except for the shortest, 1-ms deviant. Behavioural detection paralleled the MMN responses, suggesting a link between the processes underlying MMN and behavioural measures.

Ionic Mechanisms Underlying Repetitive High-Frequency Burst Firing in Supragranular Cortical Neurons

Neocortical neurons in awake, behaving animals can generate high-frequency (>300 Hz) bursts of action potentials, either in single bursts or in a repetitive manner. Intracellular recordings of layer II/III pyramidal neurons were obtained from adult ferret visual cortical slices maintained in vitro to investigate the ionic mechanisms by which a subgroup of these cells generates repetitive, high-frequency burst discharges, a pattern referred to as "chattering." The generation of each but the first action potential in a burst was dependent on the critical interplay between the afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs) that followed each action potential. The spike-afterdepolarization and the generation of action potential bursts were dependent on Na(+), but not Ca(2+), currents. Neither blocking of the transmembrane flow of Ca(2+) nor the intracellular chelation of free Ca(2+) with BAPTA inhibited the generation of intrinsic bursts. In contrast, decreasing the extracellular Na(+) concentration or pharmacologically blocking Na(+) currents with tetrodotoxin, QX-314, or phenytoin inhibited bursting before inhibiting action potential generation. Additionally, a subset of layer II/III pyramidal neurons could be induced to switch from repetitive single spiking to a burst-firing mode by constant depolarizing current injection, by raising extracellular K(+) concentrations, or by potentiation of the persistent Na(+) current with the Na(+) channel toxin ATX II. These results indicate that cortical neurons may dynamically regulate their pattern of action potential generation through control of Na(+) and K(+) currents. The generation of high-frequency burst discharges may strongly influence the response of postsynaptic neurons and the operation of local cortical networks.

Unipolar brush cell: a potential feedforward excitatory interneuron of the cerebellum

Unipolar brush cells are a class of interneurons in the granular layer of the mammalian cerebellum that receives excitatory mossy fiber synaptic input in the form of a giant glutamatergic synapse. Previously, it was shown that the unipolar brush cell axon branches within the granular layer, giving rise to large terminals. Single mossy fiber stimuli evoke a prolonged burst of firing in unipolar brush cells, which would be distributed to postsynaptic targets within the granular layer. Knowledge of the ultrastructure of the unipolar brush cell terminals and of the cellular identity of its postsynaptic targets is required to understand how unipolar brush cells contribute to information processing in the cerebellar circuit. To investigate the unipolar brush cell axon and its targets, unipolar brush cells were patch-clamped in fresh parasagittal slices from rat cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and examined by confocal fluorescence and electron microscopy. Biocytin was localized with diaminobenzidine chromogen or gold-conjugated, silver-intensified avidin. Light microscopic examination revealed a single thin axon emanating from the unipolar brush cell soma that gave rise to 2–3 axon collaterals terminating in mossy fiber-like rosettes in the granular layer, typically within a few hundred μm of the soma. In some cases, axon collaterals crossed the white matter within the same folium before terminating in the adjacent granular layer. Electron microscopic examination of serial ultrathin sections revealed that proximal unipolar brush cell axons and axon collaterals were unmyelinated and devoid of synaptic contacts. However, the rosette-shaped enlargements of each collateral formed the central component of glomeruli where they were surrounded by dendrites of granule cells and/or other unipolar brush cells, with which they formed asymmetric synaptic contacts. A long-latency repetitive burst of polysynaptic activity was observed in granule cells in this cerebellar region following white matter stimulation. The unipolar brush cell axons, therefore, form a system of cortex-intrinsic mossy fibers. The results indicate that synaptic excitation of unipolar brush cells by mossy fibers will drive a large population of granule cells, and thus will contribute a powerful form of distributed excitation within the basic circuit of the cerebellar cortex.

Sex-specific triggers for right ventricular outflow tract tachycardia

Background Right ventricular outflow tract tachycardia (RVOT-VT) is a common arrhythmia in young patients without heart disease. The arrhythmia is characterized by repetitive bursts and premature ventricular contractions with a left bundle branch block, inferior-axis QRS morphology, and symptoms of palpitations. Although more frequent in women, sex-specific triggers for symptomatic RVOT-VT have not been identified. Methods and Results We interviewed 34 women and 13 men referred for ablation of RVOT-VT to determine if predictable but sex-specific exacerbations in symptomatic RVOT-VT exist. After a general query asking if there was predictability to what triggered palpitations, we then specifically queried all patients about symptomatic RVOT-VT initiation with exercise, stress, caffeine, fatigue, and, in women only, periods of recognized hormonal flux. The times identified as states of hormonal flux included premenstrual, gestational, perimenopausal, and coincident with the administration of birth control pills. In response to the completed interview, the most common recorded trigger for RVOT-VT in women was recognized states of hormonal flux with 20 (59%) of 34 women responding positively and 14 (41%) of the 34 indicating that states of hormonal flux were the only recognizable triggers. Men were more likely than women to report that their RVOT-VT was predictably triggered by exercise, stress, or caffeine: 12 (92%) of 13 men versus 14 (41%) of 34 women (P <.01). Conclusions Triggers for RVOT-VT initiation are sex specific. Women have RVOT-VT initiation with recognized states of hormonal flux. Men more commonly have RVOT-VT initiated by exercise or stress. These data have important implications related to patient education and counseling in the setting of RVOT-VT and may influence the timing of drug treatment and electrophysiologic evaluation in selected patients. (Am Heart J 2000;139:1009-13.)

Adenosine receptor antagonists induce persistent bursting in the rat hippocampal CA3 region via an NMDA receptor-dependent mechanism.

Adenosine receptor antagonists initiate repetitive bursting activity in the CA3 region of hippocampal slices. Although some studies have suggested that this effect is irreversible, this has been difficult to establish because many adenosine antagonists wash out of brain slices extremely slowly. Furthermore the cellular mechanism that underlies persistent bursting is unknown. To resolve these issues, we studied the effects of nonselective (8-p-sulfophenyltheophylline, 8SPT, 50-100 microM), A(l)-selective (8-cyclopentyl-1, 3-dipropylxanthine, 100 nM; xanthine carboxylic acid congener, 200 nM), and A(2A)-selective (chlorostyryl-caffeine; 200 nM) adenosine antagonists in the CA3 region of rat hippocampal slices using extracellular recording. Superfusion with all of the adenosine antagonists except chlorostyryl-caffeine induced bursting, and the burst frequency after 30 min drug superfusion did not differ for the different antagonists. Most slices showed a period of rapid initial bursting, followed either by stable bursting at a lower frequency or a pattern of oscillating burst frequency. In either case, the bursting continued after drug washout. Virtually identical patterns of long-term bursting activity were observed when 8SPT was washed out or applied continuously. Control experiments using exogenous adenosine to characterize the persistence of 8SPT in tissue demonstrated >95% washout at 60 min, a time when nearly all slices still showed regular bursting activity. When the N-methyl-D-aspartate (NMDA) antagonists DL-2-amino-5-phosphonovaleric acid (AP5; 50 microM) or dizocilpine (10 microM) were applied before and during 8SPT superfusion, bursting occurred in the presence of the NMDA antagonists but did not persist once the 8SPT was washed out. AP5 had no effect on persistent bursting when applied after the initiation of spiking. The selective calcium/calmodulin-dependent protein kinase inhibitor 1-[N, O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62; 3 microM), which has been shown to block NMDA receptor-dependent synaptic plasticity in the CA1 region, also significantly decreased the long-term effect of 8SPT. Thus adenosine antagonists initiate persistent spiking in the CA3 region; this activity does not depend on continued occupation of adenosine receptors by antagonists, and can be blocked by treatments that prevent NMDA receptor-dependent plasticity.

Diurnal motor activities of the esophagus in conscious dogs.

Diurnal motor activities of the upper, middle, and lower thirds of the thoracic esophagus, the lower esophageal sphincter, and the gastric body were recorded in six conscious dogs, using extraluminal force transducers. The motor activities of the thoracic esophagus and the lower esophageal sphincter were divided into three major motility patterns: feeding, digestive, and interdigestive. Each motility pattern was basically composed of repetitive bursts of contractions that were clearly classified into type I and II according to their contractile properties. Type I bursts were peristaltic contractions initiated at the upper thoracic esophagus and sequentially propagated distally to include the sphincter. Propagation velocity and duration of type I contractions were similar in all three motility patterns, and these contractions never were propagated into the stomach. Type II bursts were nonperistaltic simultaneous contractions of the thoracic esophagus and lower sphincter appearing synchronously with phase III of gastric interdigestive migrating contractions. Amplitude and duration of type II contractions were maximal at the sphincter, suggesting initiation at that site. In nonfeeding patterns, type I contractions would clear the esophagus of refluxed gastric contents, while type II contractions would prevent reflux.

Epileptiform discharges in the human dysplastic neocortex: in vitro physiology and pharmacology.

Field potential and intracellular recordings were made in slices of human neocortical tissue obtained during surgery for the treatment of seizures associated with focal cortical dysplasia. Ictal-like epileptiform discharges, along with isolated field potentials, were induced by bath application of 4-aminopyridine (50-100 microM). Some of the isolated field potentials were associated with fast transients representing population spikes. Field potential profile analysis indicated that both types of synchronous activity had maximal negative values at 1,400 to 1,600 microm from the pia. The intracellular counterpart of the ictal-like discharge was a prolonged membrane depolarization capped by repetitive action potential burst firing. By contrast, the isolated field potentials were mirrored by long-lasting depolarizations with minimal action potential firing; only when population spikes occurred, the isolated field potentials were associated with epileptiform action potential bursting. Ictal-like discharges were abolished by either N-methyl-D-aspartate or non-N-methyl-D-aspartate receptor antagonists. In contrast, the isolated field potentials continued to occur synchronously during excitatory transmission blockade (although they lacked fast transients) but were abolished by the gamma-aminobutyric acid(A) receptor antagonist bicuculline methiodide (n = 2 slices). Our study demonstrates that focal cortical dysplasia tissue maintained in vitro has an intrinsic ability to generate ictal-like epileptiform events when challenged with 4-aminopyridine. These discharges depend on excitatory amino acid receptor-mediated mechanisms. Our results also show the presence in focal cortical dysplasia tissue of glutamatergic-independent synchronous potentials that are mainly contributed by gamma-aminobutyric acid(A) receptor-mediated conductances.

Re-entrant activity in a presubiculum–subiculum circuit generates epileptiform activity in vitro

The retrohippocampal cortices form the transition between neocortex and the hippocampus. Area CA3 of the hippocampus and the entorhinal cortex (EC) of the retrohippocampal region are established as brain regions that generate epileptiform activity. Interictal activity generated in EC consists of a primary population burst followed by multiple afterdischarges. The presubiculum is similar to EC in its six-layered structure, but lacks a columnar circuitry that the EC possesses. Isolated presubicular tissue cannot generate afterdischarges and isolated subicular tissue generates no spontaneous activity under some conditions. We report epileptiform activity in combined presubiculum–subiculum slices that consists of synchronous population bursts and multiple afterdischarges. Intracellular and field potential recordings reveal two re-entrant paths for interaction of presubicular and subicular neurons. We demonstrate a deep presubicular input to subiculum and separate return paths from subicular bursting neurons onto deep and superficial layer pre-/parasubicular neurons. Recordings from subicular cell apical dendrites showed repetitive burst firing during sustained depolarizing current injection. We conclude that re-entrant activity in a presubiculum–subiculum circuit generates epileptiform activity in both regions. Presubicular inputs to subiculum depolarize apical dendrites which can then burst repetitively. These bursts are transmitted back to the presubiculum. We suggest that iterations on this circuit act to prolong the dendritic depolarization of subicular bursting neurons and to entrain the activity across subicular cells resulting in multiple afterdischarges.