Extracellular recording of localized electrical activity in denervated frog slow muscle fibres

Pyriformis muscles of Rana temporaria were denervated by cutting the sciatic nerve in the pelvis. Slow muscle fibres were depolarized with intracellular current pulses, and the electrical activity was recorded simultaneously with intracellular and extracellular recording electrodes. When the extracellular electrode was moved along the fibre surface, outward and inward currents of variable amplitude were recorded. Inward currents coincided with the fast rising phase of the intracellularly recorded action potential; up to four inward current peaks could be detected in single fibres investigated over 3.4--8 mm of their length. The distance between inward current peaks was generally 1--2 mm, but greater distances were also observed. Composite action potentials could be shown to be due to inward currents arising in separate areas of the slow fibre membrane. It is concluded that after denervation Na-channels are incorporated into spatially limited areas of the membrane of slow muscle fibres.     

In vivo magnetic and electric recordings from nerve bundles and single motor units in mammalian skeletal muscle. Correlations with muscle force

Recent advances in the technology of recording magnetic fields associated with electric current flow in biological tissues have provided a means of examining action currents that is more direct and possibly more accurate than conventional electrical recording. Magnetic recordings are relatively insensitive to muscle movement, and, because the recording probes are not directly connected to the tissue, distortions of the data due to changes in the electrochemical interface between the probes and the tissue are eliminated. In vivo magnetic recordings of action currents of rat common peroneal nerve and extensor digitorum longus (EDL) muscle were obtained by a new magnetic probe and amplifier system that operates within the physiological temperature range. The magnetically recorded waveforms were compared with those obtained simultaneously by conventional, extracellular recording techniques. We used the amplitude of EDL twitch force (an index of stimulus strength) generated in response to graded stimulation of the common peroneal nerve to enable us to compare the amplitudes of magnetically recorded nerve and muscle compound action currents (NCACs and MCACs, respectively) with the amplitudes of electrically recorded nerve compound action potentials (NCAPs). High, positive correlations to stimulus strength were found for NCACs (r = 0.998), MCACs (r = 0.974), and NCAPs (r = 0.998). We also computed the correlations of EDL single motor unit twitch force with magnetically recorded single motor unit compound action currents (SMUCACs) and electrically recorded single motor unit compound action potentials (SMUCAPs) obtained with both a ring electrode and a straight wire serving as a point electrode. Only the SMUCACs had a relatively strong positive correlation (r = 0.768) with EDL twitch force. Correlations for ring and wire electrode-recorded SMUCAPs were 0.565 and -0.366, respectively. This study adds a relatively direct examination of action currents to the characterization of the normal biophysical properties of peripheral nerve, muscle, and muscle single motor units.     

The extracellular potential of a myelinated nerve fiber in an unbounded medium and in nerve cuff models

A model is presented for the calculation of single myelinated fiber action potentials in an unbounded homogeneous medium and in nerve cuff electrodes. The model consists of a fiber model, used to calculate the action currents at the nodes of Ranvier, and a cylindrically symmetrical volume conductor model in which the fiber's nodes are represented as point current sources. The extracellular action potentials were shown to remain unchanged if the fiber diameter and the volume conductor geometry are scaled by the same factor (principle of corresponding states), both in an unbounded homogeneous medium and in an inhomogeneous volume conductor. The influence of several cuff electrode parameters, among others, cuff length and cuff diameter, were studied, and the results were compared, where possible, with theoretical and experimental results as reported in the literature.     

Neural Adaptation and Behavioral Measures of Temporal Processing and Speech Perception in Cochlear Implant Recipients

The objective was to determine if one of the neural temporal features, neural adaptation, can account for the across-subject variability in behavioral measures of temporal processing and speech perception performance in cochlear implant (CI) recipients. Neural adaptation is the phenomenon in which neural responses are the strongest at the beginning of the stimulus and decline following stimulus repetition (e.g., stimulus trains). It is unclear how this temporal property of neural responses relates to psychophysical measures of temporal processing (e.g., gap detection) or speech perception. The adaptation of the electrical compound action potential (ECAP) was obtained using 1000 pulses per second (pps) biphasic pulse trains presented directly to the electrode. The adaptation of the late auditory evoked potential (LAEP) was obtained using a sequence of 1-kHz tone bursts presented acoustically, through the cochlear implant. Behavioral temporal processing was measured using the Random Gap Detection Test at the most comfortable listening level. Consonant nucleus consonant (CNC) word and AzBio sentences were also tested. The results showed that both ECAP and LAEP display adaptive patterns, with a substantial across-subject variability in the amount of adaptation. No correlations between the amount of neural adaptation and gap detection thresholds (GDTs) or speech perception scores were found. The correlations between the degree of neural adaptation and demographic factors showed that CI users having more LAEP adaptation were likely to be those implanted at a younger age than CI users with less LAEP adaptation. The results suggested that neural adaptation, at least this feature alone, cannot account for the across-subject variability in temporal processing ability in the CI users. However, the finding that the LAEP adaptive pattern was less prominent in the CI group compared to the normal hearing group may suggest the important role of normal adaptation pattern at the cortical level in speech perception.     

Electrophysiological control of ciliary motor responses in the ctenophorePleurobrachia

Prey capture by a tentacle of the ctenophore Pleurobrachia elicits a reversal of beat direction and increase in beat frequency of comb plates in rows adjacent to the catching tentacle (Tamm and Moss 1985). These ciliary motor responses were elicited in intact animals by repetitive electrical stimulation of a tentacle or the midsubtentacular body surface with a suction electrode. An isolated split-comb row preparation allowed stable intracellular recording from comb plate cells during electrically stimulated motor responses of the comb plates, which were imaged by high-speed video microscopy. During normal beating in the absence of electrical stimulation, comb plate cells showed no changes in the resting membrane potential, which was typically about -60 mV. Trains of electrical impulses (5/s, 5 ms duration, at 5-15 V) delivered by an extracellular suction electrode elicited summing facilitating synaptic potentials which gave rise to graded regenerative responses. High K+ artificial seawater caused progressive depolarization of the polster cells which led to volleys of action potentials. Current injection (depolarizing or release from hyperpolarizing current) also elicited regenerative responses; the rate of rise and the peak amplitude were graded with intensity of stimulus current beyond a threshold value of about -40 mV. Increasing levels of subthreshold depolarization were correlated with increasing rates of beating in the normal direction. Action potentials were accompanied by laydown (upward curvature of nonbeating plates), reversed beating at high frequency, and intermediate beat patterns. TEA increased the summed depolarization elicited by pulse train stimulation, as well as the size and duration of the action potentials. TEA-enhanced single action potentials evoked a sudden arrest, laydown and brief bout of reversed beating. Dual electrode impalements showed that cells in the same comb plate ridge experienced similar but not identical electrical activity, even though all of their cilia beat synchronously. The large number of cells making up a comb plate, their highly asymmetric shape, and their complex innervation and electrical characteristics present interesting features of bioelectric control not found in other cilia.     

Detection of motor unit action potentials with surface electrodes: influence of electrode size and spacing

A model of the motor unit action potential was developed to investigate the amplitude and frequency spectrum contributions of motor units, located at various depths within muscle, to the surface detected electromyographic (EMG) signal. A dipole representation of the transmembrane current in a three-dimensional muscle volume was used to estimate detected individual muscle fiber action potentials. The effects of anisotropic muscle conductance, innervation zone location, propagation velocity, fiber length, electrode area, and electrode configuration were included in the fiber action potential model. A motor unit action potential was assumed to be the sum of the individual muscle fiber action potentials. A computational procedure, based on the notion of isopotential layers, was developed which substantially reduced the calculation time required to estimate motor unit action potentials. The simulations indicated that: 1) only those motor units with muscle fibers located within 10–12 mm of the electrodes would contribute significant signal energy to the surface EMG, 2) variation in surface area of electrodes has little effect on the detection depth of motor unit action potentials, 3) increased interelectrode spacing moderately increases detection depth, and 4) the frequency content of action potentials decreases steeply with increased electrode-motor unit territory distance.     

A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina

Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron’s electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy.     

Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials.

The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared.     

Outward sodium current in beating heart cells.

This article is a study of the fast Na current during action potentials. We have investigated the outward Na current (Mazzanti, M., and L.J. DeFelice. 1987. Biophys. J. 52:95-100) in more detail, and we have asked whether it goes through the same channels associated with the rapid depolarization phase of action potentials. We address the question by patch clamping single, spontaneously beating, embryonic chick ventricle cells, using two electrodes to record the action potential and the patch current simultaneously. The chief limitation is the capacitive current, and in this article we describe a new method to subtract it. Varying the potential and the Na concentration in the patch pipette, and fitting the corrected currents to a standard model (Ebihara, L., and E.A. Johnson. 1980. Biophys. J. 32:779-790), provides evidence that the outward current is carried by the same channels that conduct the inward current. We compare the currents in beating cells to currents in nonbeating cells using whole-cell and cell-attached patch clamp recordings. The latter tend to show more positive Na reversal potentials, with the implication that internal Na is higher in beating cells. We propose that the plateau of the action potential, which is partly due to an inward Ca current, exceeds Na action current reversal potentials, and that this driving force gives rise to an outward movement of Na ions. The existence of such a current would imply that the fast repolarization phase after the upstroke of cardiac action potentials is partly due to the Na action current.     

Modeling a Neural Oscillator that Paces Heartbeat in the Medicinal Leech

SYNOPSIS. Heartbeat in the medicinal leech is paced by a neuraloscillator comprising two elemental oscillators whose activityis coordinated intersegmental coordinating fibers. The elementaloscillators each consist of a bilateral pair of heart interneuronslinked by reciprocal inhibitory synapses. The activity cycleof each elemental oscillator consists of alternating burstsof action potentials (plateau/burst phase) and periods inhibition(inactive phase). Oscillation ensues in the reciprocally inhibitorypairs because each neuron is able to escape from the inhibitionits contralateral partner and thus move on to the plateau/burstphase. We have identified and described membrane currents thatcontribute to oscillation and studied graded synaptic transmissionbetween the neurons, using discontinuous current clamp and switchingsingle electrode voltage clamp techniques. A hyperpolarization-activatedinward current, Ih, plays a major role in escape from inhibition,and Ca²⁺ currents produce plateau potentials that support burstformation and mediate graded synaptic transmission. To consolidate our knowledge and guide future research, we haveconstructed a first generation computer model of a neural oscillatorbased on reciprocal inhibition, using Hodgkin-Huxley equationsand a synaptic transfer model, derived from our biophysicalstudies, with Nodus software (De Schutter, 1989). This modelhas confirmed an important role for I_h in sustaining oscillationand has implicated a similarly important role for outward currents(particularly I_A), which remain to be studied. Neural oscillatorsbased on reciprocal inhibition appear to be ubiquitous, andour studies, biophysical and computational, provide insightsinto how they may operate.     

Gold nanograin microelectrodes for neuroelectronic interfaces

Neuroelectronic interfaces are imperative in investigating neural tissues as electrical signals are the main information carriers in the nervous system and metal microelectrodes have been widely used for recording and stimulation of nerve cells. For high performance microelectrodes, low tissue-electrode interfacial impedance and high charge injection limits are essential and nanoscale surface engineering has been utilized to meet the requirements for microelectrodes. We report a single-cell sized microelectrode, which has unique gold nanograin structures, using a simple electrochemical deposition method. The fabricated microelectrode had a sunflower shape with 1–5 (m of micropetals along the circumference of the microelectrode and 500 nm nanograins at the center. The nanograin electrodes had 69-fold decrease of impedance and 10-fold increase in electrical stimulation capability compared to unmodified flat gold microelectrodes. The recording and stimulation performance of nanograin electrodes was tested using dissociated rat hippocampal neuronal cultures. Noise levels were extremely low (2.89 μV_rms) resulting in high signal-to-noise ratio for low-amplitude action potentials (18.6–315 μV). Small biphasic current pulses (20–60 μA) could evoke action potentials from neurons nearby electrodes. This new nanostructured neural electrode may be applicable for the development of cell-based biosensors or clinical neural prosthetic devices.     

An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

Within the computational neuroscience community, there has been a focus on simulating the electrical activity of neurons, while other components of brain tissue, such as glia cells and the extracellular space, are often neglected. Standard models of extracellular potentials are based on a combination of multicompartmental models describing neural electrodynamics and volume conductor theory. Such models cannot be used to simulate the slow components of extracellular potentials, which depend on ion concentration dynamics, and the effect that this has on extracellular diffusion potentials and glial buffering currents. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue. The edNEG model (i) keeps track of all intraneuronal, intraglial, and extracellular ion concentrations and electrical potentials, (ii) accounts for action potentials and dendritic calcium spikes in neurons, (iii) contains a neuronal and glial homeostatic machinery that gives physiologically realistic ion concentration dynamics, (iv) accounts for electrodiffusive transmembrane, intracellular, and extracellular ionic movements, and (v) accounts for glial and neuronal swelling caused by osmotic transmembrane pressure gradients. The edNEG model accounts for the concentration-dependent effects on ECS potentials that the standard models neglect. Using the edNEG model, we analyze these effects by splitting the extracellular potential into three components: one due to neural sink/source configurations, one due to glial sink/source configurations, and one due to extracellular diffusive currents. Through a series of simulations, we analyze the roles played by the various components and how they interact in generating the total slow potential. We conclude that the three components are of comparable magnitude and that the stimulus conditions determine which of the components that dominate.     

Computational Study on Subdural Cortical Stimulation - The Influence of the Head Geometry,Anisotropic Conductivity,and Electrode Configuration

Subdural cortical stimulation (SuCS) is a method used to inject electrical current through electrodes beneath the dura mater, and is known to be useful in treating brain disorders. However, precisely how SuCS must be applied to yield the most effective results has rarely been investigated. For this purpose, we developed a three-dimensional computational model that represents an anatomically realistic brain model including an upper chest. With this computational model, we investigated the influence of stimulation amplitudes, electrode configurations (single or paddle-array), and white matter conductivities (isotropy or anisotropy). Further, the effects of stimulation were compared with two other computational models, including an anatomically realistic brain-only model and the simplified extruded slab model representing the precentral gyrus area. The results of voltage stimulation suggested that there was a synergistic effect with the paddle-array due to the use of multiple electrodes; however, a single electrode was more efficient with current stimulation. The conventional model (simplified extruded slab) far overestimated the effects of stimulation with both voltage and current by comparison to our proposed realistic upper body model. However, the realistic upper body and full brain-only models demonstrated similar stimulation effects. In our investigation of the influence of anisotropic conductivity, model with a fixed ratio (1∶10) anisotropic conductivity yielded deeper penetration depths and larger extents of stimulation than others. However, isotropic and anisotropic models with fixed ratios (1∶2, 1∶5) yielded similar stimulation effects. Lastly, whether the reference electrode was located on the right or left chest had no substantial effects on stimulation.     

Electricity production by Geobacter sulfurreducens attached to electrodes

Previous studies have suggested that members of the Geobacteraceae can use electrodes as electron acceptors for anaerobic respiration. In order to better understand this electron transfer process for energy production, Geobacter sulfurreducens was inoculated into chambers in which a graphite electrode served as the sole electron acceptor and acetate or hydrogen was the electron donor. The electron-accepting electrodes were maintained at oxidizing potentials by connecting them to similar electrodes in oxygenated medium (fuel cells) or to potentiostats that poised electrodes at +0.2 V versus an Ag/AgCl reference electrode (poised potential). When a small inoculum of G. sulfurreducens was introduced into electrode-containing chambers, electrical current production was dependent upon oxidation of acetate to carbon dioxide and increased exponentially, indicating for the first time that electrode reduction supported the growth of this organism. When the medium was replaced with an anaerobic buffer lacking nutrients required for growth, acetate-dependent electrical current production was unaffected and cells attached to these electrodes continued to generate electrical current for weeks. This represents the first report of microbial electricity production solely by cells attached to an electrode. Electrode-attached cells completely oxidized acetate to levels below detection (<10 micro M), and hydrogen was metabolized to a threshold of 3 Pa. The rates of electron transfer to electrodes (0.21 to 1.2 micro mol of electrons/mg of protein/min) were similar to those observed for respiration with Fe(III) citrate as the electron acceptor (E(o)' =+0.37 V). The production of current in microbial fuel cell (65 mA/m(2) of electrode surface) or poised-potential (163 to 1,143 mA/m(2)) mode was greater than what has been reported for other microbial systems, even those that employed higher cell densities and electron-shuttling compounds. Since acetate was completely oxidized, the efficiency of conversion of organic electron donor to electricity was significantly higher than in previously described microbial fuel cells. These results suggest that the effectiveness of microbial fuel cells can be increased with organisms such as G. sulfurreducens that can attach to electrodes and remain viable for long periods of time while completely oxidizing organic substrates with quantitative transfer of electrons to an electrode.     

Disentanglement of local field potential sources by independent component analysis

The spontaneous activity of working neurons yields synaptic currents that mix up in the volume conductor. This activity is picked up by intracerebral recording electrodes as local field potentials (LFPs), but their separation into original informative sources is an unresolved problem. Assuming that synaptic currents have stationary placing we implemented independent component model for blind source separation of LFPs in the hippocampal CA1 region. After suppressing contaminating sources from adjacent regions we obtained three main local LFP generators. The specificity of the information contained in isolated generators is much higher than in raw potentials as revealed by stronger phase-spike correlation with local putative interneurons. The spatial distribution of the population synaptic input corresponding to each isolated generator was disclosed by current-source density analysis of spatial weights. The found generators match with axonal terminal fields from subtypes of local interneurons and associational fibers from nearby subfields. The found distributions of synaptic currents were employed in a computational model to reconstruct spontaneous LFPs. The phase-spike correlations of simulated units and LFPs show laminar dependency that reflects the nature and magnitude of the synaptic currents in the targeted pyramidal cells. We propose that each isolated generator captures the synaptic activity driven by a different neuron subpopulation. This offers experimentally justified model of local circuits creating extracellular potential, which involves distinct neuron subtypes.     

The phases of small networks of chemical reactors and neurons

We present an experimental study of the phase relationships observed in small reactor networks consisting of two and three continuous flow stirred tank reactors. In the three-reactor network one chemical oscillator is coupled to two other reactors in parallel in analogy to a small neural net. Each reactor contains an identical reaction mixture of the excitable Belousov-Zhabotinsky reaction which is characterized by its bifurcation diagram, where the electrical current is the bifurcation parameter. Coupling between the reactors is electrical via Pt-working electrodes and it can be either repulsive (inhibitory) or attractive (excitatory). An external electrical stimulus is applied to all three reactors in the form of an asymmetric electrical current pulse which sweeps across the bifurcation diagram. As a consequence, all three reactors oscillate with characteristic oscillation patterns or remain silent in analogy to the firing of neurons. The observed phase behavior depends on the type of coupling in a complex way. This situation is analogous to the in vivo measurements on single neurons (local neurons and projection neurons) performed by G. Laurent and co-workers on the olfactory system of the locust. We propose a simple neural network similar to the reactor network using the Hodgkin-Huxley model to simulate the action potentials of the coupled single neurons. Analogies between the reactor network and the neural network are discussed.     

Impedance and Electrically Evoked Compound Action Potential (ECAP) Drop within 24 Hours after Cochlear Implantation

Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI) insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP) variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈2.5 cm) and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001). There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes with long-term hearing/speech performance.     

The effects of cations upon the action potentials recorded from neurohaemal tissue of the stick insect

Summary The ionic requirement for the action potentials recorded from the neurohaemal tissue on the lateral branch of the median nerve inCarausius morosus has been studied using extracellular electrodes. Sodium-free, magnesium-free, or calcium-free salines produce irreversible block of the action potentials following prolonged exposure to the nerves. Reducing the sodium concentration to 4 mM has little effect on the amplitude of the action potentials, whilst increasing the sodium concentration to 100 mM reduces the amplitude by 50%. Neither tetrodotoxin nor procaine has any effect on these action potentials.Reducing the magnesium concentration to 1 mM increases the amplitude of the action potentials, whilst increasing the concentration of magnesium reduces the amplitude.The amplitude of the action potentials is linearly related to the log of the external calcium concentration, and the action potentials are blocked by both cobalt ions and lanthanum ions.It is concluded that calcium is the major charge carrier of the inward current in these neurosecretory axons which is the first report of calcium dependent action potentials in a nerve axon. Furthermore, small amounts of sodium and magnesium are necessary to maintain electrical activity. Magnesium is a competitive inhibitor of the calcium currents.We are grateful to the Science Research Council for financial support, and to Mrs. J. Birch for the printing of the electron micrographs.     

Response of single alpha motoneurons to high-frequency pulse trains. Firing behavior and conduction block phenomenon

Studies were conducted on 25 cats to document the discharge rates of alpha motoneurons during stimulation of the sciatic nerve at frequencies from 100 to 10,000 pulses per second (pps). In addition, the feasibility of using high-frequency pulse trains to block the conduction of action potentials was investigated. Two cuff electrodes were placed around the proximal portion of the left sciatic nerve, and recordings of antidromic potentials were taken from single fibers of the L7 ventral root. When stimulating through the more proximal electrode, discharge rates were generally equal to or were subharmonics of the stimulation rate up to 1,000 pps. Firing often decreased in rate during 3-min runs. At 2,000-10,000 pps, fibers responded briefly at rates of several hundred per second but stopped firing within seconds after stimulus initiation. After cessation of response to the high-frequency pulse train, action potentials generated at 50 pps at the more distal electrode did not propagate to the recording electrodes. The 'electrical block' so induced was maintained for up to 20 min, and recovery following termination of the pulse train was complete within 1 s.