A computer system for real-time data acquisition and analysis of biopotentials and quantal content at the neuromuscular junction

A computerized data acquisition system for on-line analysis of the parameters of neuromuscular transmission is described. Both hardware usage and software methodologies are discussed with regard to sampling in real-time and analyzing miniature end-plate potentials (MEPPs), end-plate potentials (EPPs) and quantal content of the evoked transmitter release. Significant features of the program include: (1) automatic threshold determination for MEPP detection; (2) the use of a circular buffer to give pre-trigger information; (3) real-time noise spike rejection; (4) an automatic procedure for EPP failure detection; (5) rapid quantal content determinations by several methods as well as complete MEPP and EPP waveform analysis. The system has proven both accurate and reliable during more than two years of use. Advantages of the system over conventional methods include: (1) increased accuracy and efficiency in data analysis; (2) immediate availability of results; (3) conventional data storage; (4) flexibility to meet changing requirements.     

A computer system for neurosurgical patient monitoring.

The variables monitored in intensive care units are generally late indicators of neurologic deterioration. A system based on a LINC-8 computer was therefore developed for on-line monitoring of evoked potentials, electroencephalography (EEG), and transcranial and transthoracic impedances as well as conventional parameters. Somatosensory evoked potentials are recorded at either 30 min or 1 h intervals. One minute epochs of EEG are analyzed every 10 min using a peak-detection algorithm. Impedances and conventional parameters are also monitored at 10 min intervals. In a study of 50 patients, the technical feasibility of this type of monitoring with a small laboratory computer has been demonstrated. In some instances, evoked potentials and EEG show changes prior to detectable neurologic changes. The study suggests that this type of monitoring can provide a valuable adjunct for evaluation of physiologic function in neurosurgical intensive care.     

Nicardipine inhibits axon conduction but causes dual changes of acetylcholine release in the mouse motor nerve

The effects of nicardipine, a dihydropyridine Ca2(+)-channel antagonist, on neuromuscular transmission and impulse-evoked release of acetylcholine were compared with those of nifedipine. In the isolated mouse phrenic nerve diaphragm, nicardipine (50 microM), but not nifedipine (100 microM), induced neuromuscular block, fade of tetanic contraction, and dropout or all-or-none block of end-plate potentials. Nicardipine had no significant effect on the resting membrane potential and the amplitude of miniature end-plate potentials but increased the frequency and caused the appearance of large size miniature potentials. The quantal contents of evoked end-plate potentials were increased. In the presence of tubocurarine, however, nicardipine depressed the amplitude of end-plate potentials. The compound nerve action potential was also decreased. It is concluded that nicardipine blocks neuromuscular transmission by acting on Na+ channels and inhibits axonal conduction. Nicardipine appeared to affect the evoked release of acetylcholine by dual mechanisms, i.e., an enhancement presumably by an agonist action on Ca2+ channels, like Bay K 8644 and nifedipine, and inhibition by an effect on Na+ channels, like verapamil and diltiazem. In contrast with its inactivity on the amplitude of miniature end-plate potentials, depolarization of the end plate in response to succinylcholine was greatly depressed. The contractile response of baby chick biventer cervicis muscle to exogenous acetylcholine was noncompetitively antagonized by nicardipine (10 microM), but was unaffected by nifedipine (30 microM). These results may implicate that nicardipine blocks the postsynaptic acetylcholine receptor channel by enhancing receptor desensitization or by a use-dependent effect.     

Subunits in quantal transmission at the mouse neuromuscular junction: tests of peak intervals in amplitude distributions

The regular spacing of peaks throughout the amplitude distribution of miniature end-plate potentials, quantal evoked end-plate potentials and quantal currents was demonstrated using autocorrelations and power density spectra calculated from the number of events in the successive bins of the histograms built by Matteson et al. (1979), Kriebel & Florey (1983) and Erxleben & Kriebel (1984). At the same mouse neuromuscular junction, the calculated interpeak was constant for evoked and spontaneous quantal releases, throughout sequential sampling and after change of bin size. The presence of regular peak intervals supports the hypothesis that quantal potentials are composed of potential subunits the size of the smallest subminiature potential. Challenging the hypothesis of an acetylcholine quantum composed of acetylcholine subunits, a postsynaptic origin of the subunit is proposed on the basis of the spatial arrangement in rows of the ACh receptors. The ACh-saturating patch evoked by a quantum release (Land et al., 1980, 1981) activates 10-20 rows of receptors, which is roughly the number of subunits composing a quantal event. Therefore the position of the ACh patch or the continuous variations in its size might cause stepwise variations in the total number of ACh receptors activated by an ACh quantum.     

Construction of an evoked potential model expressed by parallel second order components with time lags

We propose an evoked potential model consisting of a parallel combination of second order systems with time lags. Using this evoked potential model, scalp-recorded photic evoked potentials (PEPs) of three healthy young subjects were analysed, and the PEP waveforms decomposed into five basic waveforms. Generator sources for four components commonly observed in all three subjects are discussed.     

Psychosine-induced changes in the neuromuscular transmission and structure of the neuromuscular junction in the frog

A decrease in the amplitude of the miniature and evoked end-plate potentials, as well as a change in the course of facilitation and depression of the end-plate potentials under rhythmic stimulation, were observed in psychosine-treated preparations of the cutaneous-pectoral muscle of the frog. The results of electron microscopic investigations indicate changes in the structure of synaptic Schwann cells enveloping the motor terminals and disturbances of the inner mesaxon structure of the myelinated axons.A. A. Ukhtomskii Institute of Physiology, Saint Petersburg University. Translated from Neirofiziologiya, Vol. 24, No. 4, pp. 482–490, July–August, 1992.     

Effect of sodium nitroprusside on the mediator release and functional properties of the postsynaptic membrane at the neuromuscular junction]

The effect of nitric oxide donor sodium nitroprusside on the end-plate currents was studied under two-electrode voltage-clamp condition at frog neuro-muscular junction. Sodium nitroprusside (10(-4) M) reduced to the half the amplitude of end-plate currents while did not change miniature end-plate currents indicating the presynaptic nature of end-plate depression. In keeping with such suggestion sodium nitroprusside essentially (to 33%) suppressed the frequency of miniature end-plate currents but did not affect the decay time constant and voltage-dependence of miniature end-plate decay. In contrast to another presynaptic inhibitors sodium nitroprusside rather reduced than increased the presynaptic facilitation and did not change postsynaptic potentials. Thus, nitric oxide is the powerful inhibitor of both evoked and spontaneous transmitter release and did not change postsynaptic potential.     

Effect of imidazole,guanidine, and theophylline on transmitter release in the frog neuromuscular synapse in relation to temperature and calcium ion concentration in the medium

The effects of imidazole, guanidine, and theophylline on spontaneous (frequency of miniature end-plate potentials) and evoked (quantum composition of end-plate potentials) transmitter release were compared in isolated sartorius muscles ofRana temporaria at different temperatures and during changes in the calcium concentration in the external solution. All three substances increased the quantum composition of the end-plate potentials and the frequency of the miniature end-plate potentials at 20°C and in 0.5 mM calcium. As regards their effect on the quantum composition the substances could be arranged in the following order: imidazole guanidine theophylline; as regards their effect on frequency: theophylline imidazole guanidine. Theophylline increased spontaneous release, whereas imidazole and guanidine increased evoked transmitter release more than the rest. Comparison of the effect of these substances at 20 and 7°C showed that only the action of theophylline on spontaneous release depends on temperature. The effect of imidazole and theophylline on frequency was independent of the calcium concentration in the medium. Differences in the mechanism of action of these compounds on spontaneous and evoked acetylcholine release are discussed.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 9, No. 4, pp. 430–436, July–August, 1977.     

Time coding in the midbrain of mormyrid electric fish. II. Stimulus selectivity in the nucleus exterolateralis pars posterior

The anterior and posterior exterolateral nuclei (ELa and ELp) of the mormyrid midbrain are thought to play a critical role in the temporal analysis of the electric discharge waveforms of other individuals. The peripheral electroreceptors receiving electric organ discharges (EODs) of other fish project through the brainstem to ELa via a rapid conducting pathway. EODs, composed of brief, but stereotyped waveforms are encoded as a temporal pattern of spikes. From previous work, we know that phase locking is precise in ELa. Here it is shown that evoked potentials recorded from ELp show a similar high degree of phase locking, although the evoked potentials last much longer. Single-unit recordings in ELp reveal two distinct populations of neurons in ELp: type I cells are responsive to voltage step functions, and not tuned for stimulus duration; type II cells are tuned to a specific range of stimulus durations. Type II cells are less responsive than type I cells, tend to respond with bursts of action potentials rather than with single spikes, have a longer latency, show weaker time locking to stimuli, and are more sensitive to stimulus polarity and amplitude. The stimulus selectivity of type II cells may arise from convergence of type I cell inputs. Despite the loss of rapid conduction between ELa and ELp, analysis of temporal features of waveforms evidently continues in ELp, perhaps through a system of labeled lines. Accepted: 25 June 1997     

Adaptive on-line simulation of bioreactors: Fermentation monitoring and modeling system

Summary In order to study and control fermentation processes, indirect on-line measurements and mathematical models can be used. Here an on-line model for fermentation processes is presented. The model is based on atom and partial mass balances as well as on stability equations for the protolytes. The model is given an adaptive form by including transport equations for mass transfer and expressions for the fermentation kinetics. The state of the process can be estimated on-line using the balance component of the model completed with measurement equations for the input and the output flows of the process. Adaptivity is realized by means of on-line estimation of the parameters in the transport and kinetic expressions using recursive regression analysis. On-line estimation of the kinetic and mass transfer parameters makes model-based predictions possible and enables intelligent process control while facilitating testing of the validity of the measurement variables. A practical MS-Windows 3.1 model implementation called FMMS—Fermentation Monitoring and Modeling System is shown. The system makes it easy to configure the operating conditions for a run. It uses Windows dialogs for all set-ups, model configuration parameters, elemental compositions, on-line measurement devices and signal conditioning. Advanced on-line data analysis makes it possible to plot variables against each other for easy comparison. FMMS keeps track of over 100 variables per run. These variables are either measured or estimated by the model. Assay results can also be entered and plotted during fermentation. Thus the model can be verified almost instantly. Historical fermentation runs can be re-analyzed in simulation mode. This makes it possible to examine different signal conditining filters as well as the sensitivity of the model. Combined, the data analysis and the simulation mode make it easy to test and develop model theories and new ideas.     

Estimation of the Temporal Course of Evoked Secretion of Transmitter Quanta in the Frog Neuromuscular Junction

In experiments on the cutaneothoracic muscle of the frog, we recorded, using the technique of two-electrode voltage clamp at a normal Ca²⁺ concentration (1.8 mM), multiquantum end-plate currents (EPC) and miniature uniquantum EPC (mEPC). Multiquantum signals, when compared with uniquantum currents, were characterized by longer leading and trailing edges. The quantum composition of multiquantum signals estimated according to the ratios of EPC and mEPC amplitudes was, on average, 27% lower than that calculated according to the ratios of their integral values (areas). These data demonstrate that stimulus-evoked transmitter secretion from the motor nerve endings is noticeably asynchronous. Based on the parameters of the experimental EPC and mEPC, we estimated the temporal course of evoked secretion using various techniques: spectral analysis, a system of linear equations, and Van der Kloot's method. Using convolution with uniquantum signals, we found that spectral analysis is the best technique for such estimation. Calculated parameters of the temporal course of secretion were the following: risetime 0.20 msec and decay time constant 0.33 msec. The respective distribution significantly differed from that of the synaptic delays of extracellularly recorded uniquantum EPC by longer durations (150-200%) of the leading and trailing edges. We hypothesize that these differences are related to the geometry of the junction and the temporal sequence of switching on of the active zones in the nerve ending upon their activation by spreading action potentials. Factors influencing the temporal course of evoked secretion of the transmitter in the junction under study (its asynchronicity, in particular) are discussed.     

Pharmacological elevation of cyclic AMP and transmitter release at the mouse neuromuscular junction

Intracellular recordings of spontaneous and evoked end-plate potentials have been made at the neuromuscular junction of mouse hemidiaphragms to determine a possible role of cyclic AMP (cAMP) in the release of acetylcholine from presynaptic terminals. Spontaneous release, as determined from the frequency of miniature end-plate potentials, was increased by drugs that inhibit phosphodiesterase: isobutylmethylxanthine (IBMX), SQ 20,009, theophylline, and caffeine; drugs that stimulate adenylate cyclase: forskolin, fluoride, and cholera toxin, and the stable analogue of cAMP: 8-bromo-cAMP but not dibutyryl cAMP. Release increased with time during maintained exposure to the drugs and generally followed a simple exponential time course with time constants ranging from 8 to 17 min at 20 degrees C, except for SQ 20,009 and cholera toxin which required longer exposure times for effect. The order of potency of the phosphodiesterase inhibitors was IBMX = SQ 20,009 greater than theophylline = caffeine. This is consistent with an effect mediated by an increase in cAMP concentrations within the nerve terminal. Evoked release, determined from the quantal content of the end-plate potential, was increased to a lesser extent than spontaneous release. The results are discussed with reference to the possible involvement of second messengers in the release of vesicles from nerve terminals in vertebrate synapses.     

大鼠脊髓诱发电位与脊髓损伤的关系——Ⅲ.脊髓局部损毁后电位的变化及电位来源分析

本文描述了大鼠脊髓L_1节段后柱、后索、侧索和前角的诱发电位及其损伤后的变化,并观察了切断L_4、L_5脊神经背、腹根与横断高位颈髓对电位的影响,以进行行电位来源分析。结果可见,上述四个区域的诱发电位基本由早反应三相波和晚反应组成。分别电解损毁这些部位后,电位波幅均普遍降低,晚期反应较早反应降低明显。后柱或后索受损对电位影响最大。局部损毁后可见L_1及T_(13)水平的硬膜上电位改变明显,尤其晚反应减弱、波峰平坦。反应时值与潜伏时未见明显改变。切断L_4脊神经背、腹根后、电位基本消失。去大脑对电位未见明显影响。结果表明,刺激坐骨神经诱发的脊髓电位起源于低位腰段传入神经和脊髓内多通路的兴奋传导,在一定程度上受腹根逆行活动的影响,与大脑及脊髓下行传导束活动无直接联系。脊髓诱发电位的幅度与波形改变可作为脊髓损伤的判断指标之一。     

Brain-stem trigeminal and auditory evoked potentials in multiple sclerosis: physiological insights

Thirty-six patients with multiple sclerosis were evaluated by means of brain-stem trigeminal and auditory evoked potentials. The brain-stem auditory evoked potentials (BAEPs) were abnormal in 26 patients (72.2%). Brain-stem trigeminal evoked potentials (BTEPs) yielded similar results, showing distorted waveforms and/or prolonged latencies in 25 patients (69.4%). As expected, the MRI proved to be the most efficient single test, revealing plaques in 86.4% of the patients evaluated. However, the diagnostic accuracy of MRI was lower than that provided by the combination of the BTEP and the BAEP (88.9%). Moreover, in patients having signs of brain-stem involvement, the BTEP, alone and in combination with the BAEP, proved to be more sensitive than the MRI in revealing brain-stem lesions.Correlation between clinical and BTEP findings could be found only in those patients who presented with signs of trigeminal involvement such as trigeminal neuralgia or dysesthesiae. The analysis of the BTEP waveforms showed two distinct types of abnormality — a peripheral type and a central type — suggesting plaques in distinct locations.Both the BTEP and the BAEP demonstrated a correlation with the clinical course of the disease and the condition of the patient at the time of the evaluation. Relapse of the disease was associated with a marked prolongation of the central conduction time in the BTEP and in the BAEP, suggesting the application of such studies to the monitoring of unstable patients or the evaluation of new therapeutic protocols.     

Auditory brain-stem responses evoked by electrical stimulation of the cochlear nucleus in human subjects

When auditory nerve function is lost due to surgical removal of bilateral acoustic tumors, a sense of hearing may be restored by means of an auditory brain-stem implant (ABI), which electrically stimulates the auditory pathway at the level of the cochlear nucleus. Placement of the stimulating electrodes during surgical implantation may be aided by electrically evoked auditory brain-stem responses (EABRs) recorded intra-operatively. To establish preliminary standards for human EABRs evoked by electrical stimulation of the cochlear nucleus, short-latency evoked potentials were recorded from 6 ABI patients who were either already implanted or undergoing implantation surgery. Neural responses were distinguished from stimulus artifact and equipment artifact by their properties during stimulus polarity reversal and amplitude variation. Other properties contributed to further identification of the evoked potentials as auditory responses (EABRs). The response waveforms generally had 2 or 3 waves. The peak latencies of these waves (approximately 0.3, 1.3, and 2.2 msec) and the brain-stem localization of the region from which they could be elicited are consistent with auditory brain-stem origin.     

Characteristics of spinal cord-evoked responses in man

The averaged electrical potentials evoked by the stimulation of the peripheral nerves were recorded with surface electrodes over the lumbosacral, lower thoracic and cervical spine and with epidurally placed electrodes in the cervical area. The waveforms of the lumbosacral and cervical spinal cord potentials show similar complexity reflecting peripheral and central generators. The larger negative wave with at least two components is followed by a slower positive deflection. Evoked potentials recorded over the cervical segments of the spinal cord with epidural electrodes are of much higher amplitude and more complex waveform than those recorded with surface electrodes.     

Upper and lower bounds on the non-linearity of sommation of end-plate potentials

The amplitudes of end-plate potentials are non-linearly related to the number of transmitter packets eliciting the potentials. The form of the non-linearity depends on the time-course of the change in membrane conductance as compared with the membrane time-constant. Approximate solutions for very short and very long time-constants provide upper and lower bounds on the relationship between the peak amplitude of the end-plate potential and the relative number of transmitter packets.     

A component analysis and principles derived for the understanding of evoked potentials of the brain: Studies in the hippocampus

The hippocampal averaged evoked potentials (AEPs) of the cat brain were analysed using a theoretical filtering method. Application of ideal low pass filters with different cutoff frequencies supports and enlarges previous findings and interpretations of Baar and Özesmi (1972) based on frequency characteristics of the hippocampus: This brain structure has significant beta frequency (18–35 Hz) selectivity near its typical theta (3–8 Hz) resonance. Moreover oscillatory hippocampal waveforms are predicted. The use of pass band and stop band filters allows one to derive conclusions and principles for the analysis and understanding of averaged evoked potentials in general.     

Visual acuity thresholds of juvenile loggerhead sea turtles (Caretta caretta): an electrophysiological approach

Visual evoked potentials measure dynamic properties of the visual system by recording transient electric responses of neural tissue identified to correspond to a specific visual stimulus, such as light or a striped grid. In this study, visual evoked potentials were used to test the visual acuity of juvenile loggerhead sea turtles (Caretta caretta) in water. Subject animals were fitted with a Plexiglas goggle filled with filtered seawater. Stimuli of black and white striped gratings were presented to the turtles using a slide projector directing an image onto a screen via a rotatable mirror that shifted the striped pattern laterally one-half cycle. Bioelectric activity was collected using a digital averaging computer and subdermal platinum electrodes, implanted under the head scutes directly above the optic nerve and the contralateral optic tectum. To isolate the response signal from the noise, signal averaging techniques were used when collecting visual evoked potentials. The resulting response waveforms included a robust positive-negative compound that was used to track the turtle's response to visual stimulation. Acuity thresholds for these sea turtles, which were derived from linear regressions analysis of the positive-negative compound amplitudes versus stripe size, ranged from 0.130 to 0.215. This acuity level is comparable to other inshore, shallow water marine species.