Ionic selectivity of native ATP-activated (P2X) receptor channels in dissociated neurones from rat parasympathetic ganglia

1. The relative permeability of the native P2X receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements of ATP-evoked currents in parasympathetic neurones dissociated from rat submandibular ganglia using the dialysed whole-cell patch clamp technique. 2. The P2X receptor-channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Na+ > Li+ > Cs+ > Rb+ > K+, and permeability ratios relative to Cs+ (P-X/P-Cs) ranging from 1. 11 to 0.86. 3. The selectivity for the divalent alkaline earth cations was also weak with the sequence Ca2+ > Sr2+ > Ba2+ > Mn2+ > Mg2+. ATP-evoked currents were strongly inhibited when the extracellular divalent cation concentration was increased. 4, The calculated permeability ratios of different ammonium cations are higher than those of the alkali metal cations. The permeability sequence obtained for the saturated organic cations is inversely correlated with the size of the cation. The unsaturated organic cations have a higher permeability than that predicted by molecular size. 5. Acidification to pH 6.2 increased the ATP-induced current amplitude twofold, whereas alkalization to 8.2 and 9.2 markedly reduced current amplitude. Cell dialysis with either anti-P2X(2) and/or anti-P2X(4) but not anti-P2X(1) antibodies attenuated the ATP-evoked current amplitude. Taken together, these data are consistent with homomeric and/or heteromeric P2X(2) and P2X(4) receptor subtypes expressed in rat submandibular neurones. 6. The permeability ratios for the series of monovalent organic cations, with the exception of unsaturated cations, were approximately related to the ionic size. The relative permeabilities of the monovalent inoganic and organic cations tested are similar to those reported previously for cloned rat P2X2 receptors expressed in mammalian cells.

Developmental changes in hyperpolarization-activated currents I-h and I-K(IR) in isolated rat intracardiac neurons

The hyperpolarization-activated nonselective cation current, I-h, was investigated in neonatal and adult rat intracardiac neurons. I-h was observed in all neurons studied and displayed slow time-dependent rectification. I-h was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of I-h was approximately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as compared with adult (-2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of I-h was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, I-K(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. I-K(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of -0.6 pA/pF at -130 mV. I-K(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I-K(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of I-K(IR). I-K(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in I-h may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.

An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies

The purpose of this study, was to develop a newborn piglet model of hypoxia/ischaemia which would better emulate the clinical situation in the asphyxiated human neonate and produce a consistent degree of histopathological injury following the insult. One-day-old piglets (n = 18) were anaesthetised with a mixture of propofol (10 mg/kg/h) and alfentinal (5,5.5 mug/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were monitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO(2)) to 3-4% and adjusting FiO(2) to maintain the cerebral function monitor peak amplitude at less than or equal to5 muV. The duration of the mild insult was 20, min while the severe insult was 30 min which included 10 min where the blood pressure was allowed to fall below 70% of baseline. Control piglets (n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthesia then euthanased 72 It after the insult. The brains were perfusion-fixed, removed and embedded in paraffin. Coronal sections were stained by haematoxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippocampus, basal ganglia, thalamus and cerebellum for the degree of damage. The total mean histology score for the five areas of the brain for the severe insult was 15.6 +/-4.4 (mean +/-S.D., n=7), whereas no damage was seen in either the mild insult (n=4) or control groups. This 'severe damage' model produces a consistent level of damage and will prove useful for examining potential neuroprotective therapies in the neonatal brain. (C) 2001 Elsevier Science BY. All rights reserved.

Preprocessing and time-frequency analysis of newborn EEG seizures

Neurological disease or dysfunction in newborn infants is often first manifested by seizures. Prolonged seizures can result in impaired neurodevelopment or even death. In adults, the clinical signs of seizures are well defined and easily recognized. In newborns, however, the clinical signs are subtle and may be absent or easily missed without constant close observation. This article describes the use of adaptive signal processing techniques for removing artifacts from newborn electroencephalogram (EEG) signals. Three adaptive algorithms have been designed in the context of EEG signals. This preprocessing is necessary before attempting a fine time-frequency analysis of EEG rhythmical activities, such as electrical seizures, corrupted by high amplitude signals. After an overview of newborn EEG signals, the authors describe the data acquisition set-up. They then introduce the basic physiological concepts related to normal and abnormal newborn EEGs and discuss the three adaptive algorithms for artifact removal. They also present time-frequency representations (TFRs) of seizure signals and discuss the estimation and modeling of the instantaneous frequency related to the main ridge of the TFR.

Detection and description of non-linear interdependence in normal multichannel human EEG data

Objectives: This study examines human scalp electroencephalographic (EEG) data for evidence of non-linear interdependence between posterior channels. The spectral and phase properties of those epochs of EEG exhibiting non-linear interdependence are studied. Methods: Scalp EEG data was collected from 40 healthy subjects. A technique for the detection of non-linear interdependence was applied to 2.048 s segments of posterior bipolar electrode data. Amplitude-adjusted phase-randomized surrogate data was used to statistically determine which EEG epochs exhibited non-linear interdependence. Results: Statistically significant evidence of non-linear interactions were evident in 2.9% (eyes open) to 4.8% (eyes closed) of the epochs. In the eyes-open recordings, these epochs exhibited a peak in the spectral and cross-spectral density functions at about 10 Hz. Two types of EEG epochs are evident in the eyes-closed recordings; one type exhibits a peak in the spectral density and cross-spectrum at 8 Hz. The other type has increased spectral and cross-spectral power across faster frequencies. Epochs identified as exhibiting non-linear interdependence display a tendency towards phase interdependencies across and between a broad range of frequencies. Conclusions: Non-linear interdependence is detectable in a small number of multichannel EEG epochs, and makes a contribution to the alpha rhythm. Non-linear interdependence produces spatially distributed activity that exhibits phase synchronization between oscillations present at different frequencies. The possible physiological significance of these findings are discussed with reference to the dynamical properties of neural systems and the role of synchronous activity in the neocortex. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Genetic sources of covariation among P3(00) and online performance variables in a delayed-response working memory task

Genetic and environmental sources of covariation among the P3(00) and online performance elicited in a delayed-response working memory task, and psychometric IQ assessed by the multidimensional aptitude battery, were examined in an adolescent twin sample. An association between frontal P3 latency and task performance (phenotypic r = -0.33; genotypic r = -0.49) was indicated, with genes (i.e. twin status) accounting for a large part of the covariation ( > 70%). In contrast, genes influencing P3 amplitude mediated only a small part (2%) of the total genetic variation in task performance. While task performance mediated 15% of the total genetic variation in IQ (phenotypic r = 0.22; genotypic r = 0.39) there was no association between P3 latency and IQ or P3 amplitude with IQ. The findings provide some insight into the inter-relationships among psychophysiological, performance and psychometric measures of cognitive ability, and provide support for a levels-of-processing genetic model of cognition where genes act on specific sub-components of cognitive processes.

Atom lasers, coherent states, and coherence II. Maximally robust ensembles of pure states

As discussed in the preceding paper [Wiseman and Vaccaro, preceding paper, Phys. Rev. A 65, 043605 (2002)], the stationary state of an optical or atom laser far above threshold is a mixture of coherent field states with random phase, or, equivalently, a Poissonian mixture of number states. We are interested in which, if either, of these descriptions of rho(ss) as a stationary ensemble of pure states, is more natural. In the preceding paper we concentrated upon the question of whether descriptions such as these are physically realizable (PR). In this paper we investigate another relevant aspect of these ensembles, their robustness. A robust ensemble is one for which the pure states that comprise it survive relatively unchanged for a long time under the system evolution. We determine numerically the most robust ensembles as a function of the parameters in the laser model: the self-energy chi of the bosons in the laser mode, and the excess phase noise nu. We find that these most robust ensembles are PR ensembles, or similar to PR ensembles, for all values of these parameters. In the ideal laser limit (nu=chi=0), the most robust states are coherent states. As the phase noise or phase dispersion is increased through nu or the self-interaction of the bosons chi, respectively, the most robust states become more and more amplitude squeezed. We find scaling laws for these states, and give analytical derivations for them. As the phase diffusion or dispersion becomes so large that the laser output is no longer quantum coherent, the most robust states become so squeezed that they cease to have a well-defined coherent amplitude. That is, the quantum coherence of the laser output is manifest in the most robust PR ensemble being an ensemble of states with a well-defined coherent amplitude. This lends support to our approach of regarding robust PR ensembles as the most natural description of the state of the laser mode. It also has interesting implications for atom lasers in particular, for which phase dispersion due to self-interactions is expected to be large.

An in situ study of photosynthetic oxygen exchange and electron transport rate in the marine macroalga Ulva lactuca (Chlorophyta)

Direct comparisons between photosynthetic O-2 evolution rate and electron transport rate (ETR) were made in situ over 24 h using the benthic macroalga Ulva lactuca (Chlorophyta), growing and measured at a depth of 1.8 m, where the midday irradiance rose to 400-600 mumol photons m(-2) s(-1). O-2 exchange was measured with a 5-chamber data-logging apparatus and ETR with a submersible pulse amplitude modulated (PAM) fluorometer (Diving-PAM). Steady-state quantum yield ((Fm'-Ft)/Fm') decreased from 0.7 during the morning to 0.45 at midday, followed by some recovery in the late afternoon. At low to medium irradiances (0-300 mumol photons m(-2) s(-1)), there was a significant correlation between O-2 evolution and ETR, but at higher irradiances, ETR continued to increase steadily, while O-2 evolution tended towards an asymptote. However at high irradiance levels (600-1200 mumol photons m-(2) s(-1)) ETR was significantly lowered. Two methods of measuring ETR, based on either diel ambient light levels and fluorescence yields or rapid light curves, gave similar results at low to moderate irradiance levels. Nutrient enrichment (increases in [NO3-], [NH4+] and [HPO42-] of 5- to 15-fold over ambient concentrations) resulted in an increase, within hours, in photosynthetic rates measured by both ETR and O-2 evolution techniques. At low irradiances, approximately 6.5 to 8.2 electrons passed through PS II during the evolution of one molecule of O-2, i.e., up to twice the theoretical minimum number of four. However, in nutrient-enriched treatments this ratio dropped to 5.1. The results indicate that PAM fluorescence can be used as a good indication of the photosynthetic rate only at low to medium irradiances.

Controlling the complex Lorenz equations by modulation

We demonstrate that a system obeying the complex Lorenz equations in the deep chaotic regime can be controlled to periodic behavior by applying a modulation to the pump parameter. For arbitrary modulation frequency and amplitude there is no obvious simplification of the dynamics. However, we find that there are numerous windows where the chaotic system has been controlled to different periodic behaviors. The widths of these windows in parameter space are narrow, and the positions are related to the ratio of the modulation frequency of the pump to the average pulsation frequency of the output variable. These results are in good agreement with observations previously made in a far-infrared laser system.

Fatigue-related changes in torque output and electromyographic parameters of trunk muscles during isometric axial rotation exertion - An investigation in patients with back pain and in healthy subjects

Study Design. A cross-sectional case-control study. Objectives. To examine the effect of fatigue on torque output as well as electromyographic frequency and amplitude values of trunk muscles during isometric axial rotation exertion in back pain patients and to compare the results with a matched control group. Summary of Background Data. Back pain patients exhibited different activation strategies in trunk muscles during the axial rotation exertions. Fatigue changes of abdominal and back muscles during axial rotation exertion have not been examined in patients with back pain. Methods. Twelve back pain patients and 12 matched controls performed isometric fatiguing axial rotation to both sides at 80% maximum voluntary contraction in a standing position. During the fatiguing exertion, electromyographic changes of rectus abdominis, external oblique, internal oblique, latissimus dorsi, iliocostalis lumborum, and multifidus were recorded bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured. Results. No difference in the endurance capacity was found between back pain and control groups. At the initial period of the exertion, back pain patients demonstrated a statistical trend (P = 0.058) of greater sagittal coupling torque as well as lower activity of rectus abdominis and multifidus and higher activity in external oblique. During the fatigue process similar changes of coupling torque were demonstrated in both sagittal and coronal planes, but a smaller fatigue rate for right external oblique, increase in median frequency for latissimus dorsi, and lesser increase in activity for back muscles were found in the back pain group compared with the control group. Conclusions. Alterations in electromyographic activation and fatigue rates of abdominal and back muscles demonstrated during the fatigue process provide insights into the muscle dysfunctions in back pain and may help clinicians to devise more rational treatment strategies.

Numerical investigations of flow and energy fields near a thermoacoustic couple

The flow field and the energy transport near thermoacoustic couples are simulated using a 2D full Navier-Stokes solver. The thermoacoustic couple plate is maintained at a constant temperature; plate lengths, which are short and long compared with the particle displacement lengths of the acoustic standing waves, are tested. Also investigated are the effects of plate spacing and the amplitude of the standing wave. Results are examined in the form of energy vectors, particle paths, and overall entropy generation rates. These show that a net heat-pumping effect appears only near the edges of thermoacoustic couple plates, within about a particle displacement distance from the ends. A heat-pumping effect can be seen even on the shortest plates tested when the plate spacing exceeds the thermal penetration depth. It is observed that energy dissipation near the plate increases quadratically as the plate spacing is reduced. The results also indicate that there may be a larger scale vortical motion outside the plates which disappears as the plate spacing is reduced. (C) 2002 Acoustical Society of America.

Long-lasting synaptic modification in the rat hippocampus resulting from NMDA receptor blockade during development

Recent reports have suggested that proper maturation of synapses in the hippocampus requires activation of NMDA receptors. We previously demonstrated that neonatal ethanol exposure results in a lasting reduction in synaptic strength in the hippocampus. To determine if this reduction was due to ethanol's effects on NMDA receptors, we investigated long-term changes in synaptic properties resulting from administration of NMDA receptor antagonists to neonatal animals. Rats were injected daily from PND 4-9 with either the noncompetitive NMDA receptor antagonist MK-801, the competitive NMDA receptor antagonist CPP, or the AMPA receptor antagonist NBQX. Control rats were either injected daily with physiological saline during the same period or left to develop normally. Hippocampal slices were prepared from nembutal-anesthetized animals between PND 35 and PND 40. The maximum pEPSP and PS values were not significantly different between controls and NMDA antagonist-treated animals. However, slices from animals injected with NMDA receptor antagonists required higher stimulus currents to attain comparable pEPSPs. The ratio of the slope of the pEPSP to the amplitude of the presynaptic volley was also reduced, as were pEPSP responses to specific stimulus currents. None of these effects were observed in slices prepared from animals treated with the AMPA receptor antagonist NBQX. Glutamate receptor antagonism did not produce lasting changes in long-term potentiation or paired-pulse facilitation. These results indicate activation of NMDA receptors during development is necessary for proper development of synapses. (C) 2001 Wiley-Liss, Inc.

Quadriceps concentric and eccentric exercise 1: Changes in contractile and electrical activity following eccentric and concentric exercise

The purpose of this study was to determine whether or not losses of strength or endurance following eccentric and concentric exercise are associated with reduced excitation. The effects of eccentric and concentric work on maximal voluntary isometric contraction (MVC) and surface electromyogram (EMG) of the quadriceps were studied in 10 healthy male subjects following bench-stepping for 20 min with a constant leading leg. Prior to stepping and at 0, 0.25, 0.50, 0.75, 1, 3. 24 and 48 h afterwards the subjects performed a 30 s leg extension MVC with each leg during which the isometric force and the root mean square voltage of the EMG were recorded. In the eccentrically exercised muscles (ECC), MVC0-3 (force during the first 3 s of contraction) fen immediately after the bench-stepping exercise to 88 +/- 2% (mean SE) of the pre-exercise value and remained significantly lower than the concentrically exercised muscles (p < 0.05). The muscle weakness in the ECC could not be attributed to central fatigue as surface EMG amplitude at MVC0-3 increased during the recovery period. Muscle weakness after eccentric exercise appears to be due to contractile failure, which is not associated with a reduction in excitation as assessed by surface EMG. Muscular fatigue over 30 s did not change in the two muscle groups after exercise (p = 0.79), indicating that the ECC were weaker but not more fatiguable after exercise.

A normative study of distortion product otoacoustic emissions in six-year-old school children

Evoked otoacoustic emissions have demonstrated potential for application in the community-based hearing screening of paediatric populations. Distortion-product otoacoustic emissions (DPOAEs), as opposed to transient evoked otoacoustic emissions (TEOAEs), have not been extensively researched in this regard. The current study aimed to describe the range of DPOAE values obtained in a large cohort (1576 ears) of 6-year-old children in school settings and to examine possible ear asymmetry, gender and history of ear infection effects on the data. Results indicated a variety of significant effects, particularly in the high frequencies, for DPOAE signal-to-noise ratio. The measurement parameter, DPOAE amplitude (DP-amp), was found to display potentially less clinical applicability due to large standard deviation values. Use of descriptive normative data, as derived in the present investigation, may contribute toward future improvements in the hearing screening of 6-year-old schoolchildren

Role of peripheral afference during acquisition of a complex coordination task

It has long been supposed that the interference observed in certain patterns of coordination is mediated, at least in part, by peripheral afference from the moving limbs. We manipulated the level of afferent input, arising from movement of the opposite limb, during the acquisition of a complex coordination task. Participants learned to generate flexion and extension movements of the right wrist, of 75degrees amplitude, that were a quarter cycle out of phase with a 1-Hz sinusoidal visual reference signal. On separate trials, the left wrist either was at rest, or was moved passively by a torque motor through 50degrees, 75degrees or 100degrees, in synchrony with the reference signal. Five acquisition sessions were conducted on successive days. A retention session was conducted I week later. Performance was initially superior when the opposite limb was moved passively than when it was static. The amplitude and frequency of active movement were lower in the static condition than in the driven conditions and the variation in the relative phase relation across trials was greater than in the driven conditions. In addition, the variability of amplitude, frequency and the relative phase relation during each trial was greater when the opposite limb was static than when driven. Similar effects were expressed in electromyograms. The most marked and consistent differences in the accuracy and consistency of performance (defined in terms of relative phase) were between the static condition and the condition in which the left wrist was moved through 50degrees. These outcomes were exhibited most prominently during initial exposure to the task. Increases in task performance during the acquisition period, as assessed by a number of kinematic variables, were generally well described by power functions. In addition, the recruitment of extensor carpi radialis (ECR), and the degree of co-contraction of flexor carpi radialis and ECR, decreased during acquisition. Our results indicate that, in an appropriate task context, afferent feedback from the opposite limb, even when out of phase with the focal movement, may have a positive influence upon the stability of coordination.