Biomedical subjects

D M Durand

Publications and source records attributed to D M Durand.

At least 37 records · Page 2Linked to original sources

PubMed1999

Chronic recordings of hypoglossal nerve activity in a dog model of upper airway obstruction.

The activity of the hypoglossal nerve was recorded during pharyngeal loading in sleeping dogs with chronically implanted cuff electrodes. Three self-coiling spiral-cuff electrodes were implanted in two beagles for durations of 17, 7, and 6 mo. During quiet wakefulness and sleep, phasic hypoglossal activity was either very small or not observable above the baseline noise. Applying a perpendicular force on the submental region by using a mechanical device to narrow the pharyngeal airway passage increased the phasic hypoglossal activity, the phasic esophageal pressure, and the inspiratory time in the next breath during non-rapid-eye-movement sleep. The phasic hypoglossal activity sustained at the elevated level while the force was present and increased with increasing amounts of loading. The hypoglossal nerve was very active in rapid-eye-movement sleep, especially when the submental force was present. The data demonstrate the feasibility of chronic recordings of the hypoglossal nerve with cuff electrodes and show that hypoglossal activity has a fast and sustained response to the internal loading of the pharynx induced by applying a submental force during non-rapid-eye-movement sleep.

Airway Obstruction↗

PubMed1999

Modulation of burst frequency, duration, and amplitude in the zero-Ca(2+) model of epileptiform activity.

Incubation of hippocampal slices in zero-Ca(2+) medium blocks synaptic transmission and results in spontaneous burst discharges. This seizure-like activity is characterized by negative shifts (bursts) in the extracellular field potential and a K(+) wave that propagates across the hippocampus. To isolate factors related to seizure initiation, propagation, and termination, a number of pharmacological agents were tested. K(+) influx and efflux mechanisms where blocked with cesium, barium, tetraethylammonium (TEA), and 4-aminopyridine (4-AP). The effect of the gap junction blockers, heptanol and octanol, on zero-Ca(2+) bursting was evaluated. Neuronal excitability was modulated with tetrodotoxin (TTX), charge screening, and applied electric fields. Glial cell function was examined with a metabolism antagonist (fluroacetate). Neuronal hyperpolarization by cation screening or applied fields decreased burst frequency but did not affect burst amplitude or duration. Heptanol attenuated burst amplitude and duration at low concentration (0.2 mM), and blocked bursting at higher concentration (0.5 mM). CsCl(2) (1 mM) had no effect, whereas high concentrations (1 mM) of BaCl(2) blocked bursting. TEA (25 mM) and low concentration of BaCl(2) (300 microM) resulted in a two- to sixfold increase in burst duration. Fluroacetate also blocked burst activity but only during prolonged application (>3 h). Our results demonstrate that burst frequency, amplitude, and duration can be independently modulated and suggest that neuronal excitability plays a central role in burst initiation, whereas potassium dynamics establish burst amplitude and duration.

4-Aminopyridine↗

PubMed1998

Influence of pulse sequence, polarity and amplitude on magnetic stimulation of human and porcine peripheral nerve.

1. Mammalian phrenic nerve, in a trough filled with saline, was excited by magnetic coil (MC)-induced stimuli at defined stimulation sites, including the negative-going first spatial derivative of the induced electric field along a straight nerve, at a bend in the nerve, and at a cut nerve ending. At all such sites, the largest amplitude response for a given stimulator output setting was elicited by an induced damped polyphasic pulse consisting of an initial quarter-cycle hyperpolarization followed by a half-cycle depolarization compared with a predominantly 'monophasic' quarter-cycle depolarization. 2. Simulation studies demonstrated that the increased efficacy of the induced quarter-cycle hyperpolarizing-half-cycle depolarizing polyphasic pulse was mainly attributed to the greater duration of the outward membrane current phase, resulting in a greater outward charge transfer afforded by the half-cycle (i.e. quarter-cycles 2 and 3). The advantage of a fast rising initial quarter-cycle depolarization was more than offset by the slower rising, but longer duration depolarizing half-cycle. 3. Simulation further revealed that the quarter-cycle hyperpolarization-half-cycle depolarization showed only a 2.6 % lowering of peak outward current and a 3.5 % lowering of outward charge transfer at threshold, compared with a half-cycle depolarization alone. Presumably, this slight increase in efficacy reflects modest reversal of Na+ inactivation by the very brief initial hyperpolarization. 4. In vitro, at low bath temperature, the nerve response to an initial quarter-cycle depolarization declined in amplitude as the second hyperpolarizing phase progressively increased in amplitude and duration. This 'pull-down' phenomenon nearly disappeared as the bath temperature approached 37 C. Possibly, at the reduced temperature, delay in generation of the action potential permitted the hyperpolarization phase to reduce excitation. 5. Pull-down was not observed in the thenar muscle responses to median nerve stimulation in a normal human at normal temperature. However, pull-down emerged when the median nerve was cooled by placing ice over the forearm. 6. In a nerve at subnormal temperature straddled with non-conducting inhomogeneities, polyphasic pulses of either polarity elicited the largest responses. This was also seen when stimulating distal median nerve at normal temperature. These results imply excitation by hyperpolarizing-depolarizing pulse sequences at two separate sites. Similarly, polyphasic pulses elicited the largest responses from nerve roots and motor cortex. 7. The pull-down phenomenon has a possible clinical application in detecting pathologically slowed activation of Na+ channels. The current direction of the polyphasic waveform may become a significant factor with the increasing use of repetitive magnetic stimulators which, for technical reasons, induce a cosine-shaped half-cycle, preceded and followed by quarter-cycles of opposite polarity.

Animals↗

PubMed1998

Effects of applied currents on spontaneous epileptiform activity induced by low calcium in the rat hippocampus.

It is known that both applied and endogenous electrical fields can modulate neuronal activity. In this study, we have demonstrated that anodic current injections can inhibit spontaneous epileptiform events in the absence of synaptic transmission. Activity was induced with low-Ca2+ (0.2 mM) artificial cerebrospinal fluid (ACSF) and detected with a voltage threshold detector. At the onset of an event, a current was injected into the stratum pyramidale via a tungsten electrode positioned within 150 micron of the recording site. Data was recorded with a glass pipette electrode. The results show that spontaneous epileptiform activity can be fully suppressed by subthreshold anodic currents with an average amplitude of 3.9 microA and a minimum amplitude of 1 microA. In addition, we observed that some events could be blocked by current pulses with shorter durations than the duration of the event itself. The possibility that increased tissue resistance could contribute to the efficacy of the currents was tested by measuring the step-potential increase evoked by anodic current injections. The data show a significant increase in the amplitude of the evoked potential after introduction of a low-Ca2+ medium, suggesting that tissue resistance is increasing. These results indicate that low-amplitude, subthreshold current pulses are sufficient to block epileptiform activity in a low-Ca2+ environment. The increased tissue resistance induced by sustained exposure to a low-Ca2+ medium could contribute to the low current amplitudes required to block the epileptiform events.

Animals↗

PubMed1998

System for dynamic measurements of membrane capacitance in intact epithelial monolayers.

Dynamic measurements of exocytosis have been difficult to perform in intact epithelial monolayers. We have designed a system that estimates with +/-1% accuracy (99% confidence) the total membrane capacitance of monolayers represented by a lumped model. This impedance measurement and analysis system operates through a conventional transepithelial electrophysiology clamp, performing all signal measurements as frequently as every 5 s. Total membrane capacitance (the series combination of apical and basolateral membranes) is the inverse of one of three unique coefficients that describe the monolayer impedance. These coefficients are estimated using a weighted, nonlinear, least-squares algorithm. Using the estimated coefficients, solution ranges for individual membrane parameters are calculated, frequently providing results within +/-20% of true values without additional electrophysiological measurements. We determined the measurement system specifications and statistical significance of estimated parameters using 1) analytical testing with circuit simulation software and equation-generated data; 2) a system noise analysis combined with Monte Carlo simulations; and 3) analog model circuits for calibration of the electronic system and to check equation-generated results. Finally, the time course of capacitance changes associated with purinergically stimulated mucin exocytosis are quantified in monolayers of the colonic goblet cell-like cell line HT29-CI.16E.

Algorithms↗

PubMed1998

Improved nerve cuff electrode recordings with subthreshold anodic currents.

A method has been developed for improving the signal amplitudes of the recordings obtained with nerve cuff electrodes. The amplitude of the electroneurogram (ENG) has been shown to increase with increasing distance between the contacts when cuff electrodes are used to record peripheral nerve activity [9]. The effect is directly related to the propagation speed of the action potentials. Computer simulations have shown that the propagation velocity of action potentials in a length of a nerve axon can be decreased by subthreshold extracellular anodic currents. Slowing the action potentials is analogous to increasing the cuff length in that both result in longer intercontact delays, thus, larger signal outputs. This phenomenon is used to increase the amplitudes of whole nerve recordings obtained with a short cuff electrode. Computer simulations predicting the slowing effect of anodic currents as well as the experimental verification of this effect are presented. The increase in the amplitude of compound action potentials (CAP's) is demonstrated experimentally in an in vitro preparation. This method can be used to improve the signal-to-noise ratios when recording from short nerve segments where the cuff length is limited.

Action Potentials↗

PubMed1998

Activation kinetics of the delayed rectifier potassium current of bullfrog sympathetic neurons.

We examined the activation kinetics of the delayed rectifier K+ current of bullfrog sympathetic neurons, primarily using whole cell recording. On depolarization, currents activated with a sigmoid delay but did not show a Cole-Moore shift. The time course of activation differed systematically from an exponential raised to a power. At most voltages, a power of 2 gave the best overall fit but a power of 3 better described the initial delay. After the delay, the time course could be fitted by a single exponential. Time constants were 15-20 ms at 0 mV and decreased to a limiting tau = 7 ms at +50 to +100 mV. Tail currents were well fitted by single exponential functions and accelerated with hyperpolarization, from tau = 15-20 ms at 0 mV to tau = 2 ms at -110 mV (e-fold for 40 mV). Eleven kinetic models were evaluated for their ability to describe the activation kinetics of the delayed rectifier. Hodgkin-Huxley-like models did not fit the data well. A linear model where voltage sensor movement is followed by a distinct channel opening step, allosteric models based on the Monod-Wyman--Changeux model, and an unconstrained C-C-C-O model could describe whole cell data from -100 to +40 mV. After including whole cell data at +60 and +80 mV, and a maximal p(open) of 0.8 from noise analysis of cell-attached patches, an allosteric model fit the data best, as the other models had difficulty describing qualitative features of the data. However, some more complex schemes (with additional free parameters) cannot be excluded. We propose the allosteric model as an empirical description of macroscopic ionic currents, and as a model worth considering in future studies on the molecular mechanism of potassium channel gating.

Animals↗

PubMed1997

Axonal stimulation under MRI magnetic field z gradients: a modeling study.

The stimulation of axons under MRI magnetic fields is analyzed solving the cable equation along the axons in the presence of magnetic field z gradients. Axons are represented using a one-dimensional compartmental cable model including the kinetics of mammalian myelinated fibers. Computer simulations of the model were performed for sinusoidal and trapezoidal fields. Several axon and field parameters were tested to determine the threshold values for axonal stimulation of the magnetic field, induced electric field and time derivative of the magnetic field. The results indicate that 1) threshold for stimulation is lowest for the largest diameter axons terminating in the region where the magnetic field is maximum, 2) trapezoidal waveforms can be optimized to allow better sub-threshold resolution than sinusoidal waveforms, and 3) the induced electric field is better than the magnetic field and time derivative of the magnetic field as indicators of stimulation threshold.

Animals↗

PubMed1997

Theoretical study of magnetic field of current monopoles in special volume conductor using symmetry analysis.

We derive a formula for the magnetic field outside volume conductors having axial symmetry with radial and axial symmetrically distributed source currents. The magnetic field is shown to have components only along the cylindrical polar angle direction and its magnitude to depend only on the topological structure of the volume conductor and the location of the source current. With this formula, the magnetic field generated by the volume current of a current monopole within and on the symmetrical axis of several volume conductors (such as semi-infinite volume, infinite slab, sphere, infinite cylinder, semi-infinite cylinder, finite cylinder, prolate spheroid, and oblate spheroid) is shown to be equivalent to the magnetic field generated by a line current calculated using the Biot-Savart's law. In the first three volume conductors, the monopole solution of the magnetic field allows the calculation of magnetic fields generated by arbitrarily distributed (and balanced for finite volume conductors) current monopoles.

Biophysical Phenomena↗

PubMed1997

Parameter estimation by reduced-order linear associative memory (ROLAM).

In a series of papers we have shown that nonlinear parameter estimation by linear association provides accurate estimates of the parameters in complex systems described by nonlinear differential equations even in the presence of additive white noise of considerable power. The technique is based on linearly associating the system's output with a set of parameter values spanning the region of interest. When an actual output is measured, the system's unknown parameters could be estimated by a matrix inversion. The size of the inverted matrix, being equal to the length of the output vector, poses a limiting factor upon the generalization of the technique. In this paper we propose a modification which requires the inversion of a matrix whose dimension equals the number of model parameters. The modified version is called reduced-order associative memory (ROLAM). The technique is applied to two complex lumped-parameter nonlinear models: the Van der Pol relaxation oscillator and the passive neuron model of the granule cells. Results validate ROLAM as a parameter-estimation tool which is especially suited in cases where the number of parameters is large, the number of samples in the observation signal is high, or when on-line parameter estimation is required. It is also shown that ROLAM provides an optimal parameter estimate in the special case of single-parameter nonlinear models.

Algorithms↗

PubMed1997

A slowly penetrating interfascicular nerve electrode for selective activation of peripheral nerves.

To meet the future needs of functional electrical stimulation (FES) applications, peripheral nerve electrodes must be able to safely, selectively, and independently stimulate small subpopulations of the axons within a common nerve trunk. A new electrode has been designed to place contacts outside of the perineurium, but within the epineurium of the nerve. This slowly penetrating interfascicular nerve electrode (SPINE) combines the safety and simplicity of extraneural cuff electrodes with the intimate interface of intrafascicular wire and probe electrodes. We briefly discuss a mathematical method of quantifying performance of nerve electrodes based on the functional output of the intact neuromuscular system. The quantification involves three variables: 1) the functional recruitment trajectory (FRT), 2) functional overlap (O), and 3) overall functional selectivity (lambda). Second, we present results from six acute SPINE implants on the feline sciatic nerve. Quantification of stimulation results demonstrate interfascicular stimulation is functionally different than extraneural stimulation in 32 of 38 trials. In 19 of 28 trials, interfascicular stimulation is functionally selective based on depth of penetration and 52 of 58 trials demonstrate selectivity based on the side of the penetrating element. Third, tissue sections show that the SPINE electrode penetrates into the nerve within 24 h without evidence of edema or damage to the perineurium.

Animals↗

PubMed1997

Spiral nerve cuff electrode for recordings of respiratory output.

The feasibility of using the spiral nerve cuff electrode design for recordings of respiratory output from the hypoglossal (HG) and phrenic nerves is demonstrated in anesthetized, paralyzed, and artificially ventilated cats. Raw neural discharges of the HG nerve were analyzed in terms of signal-to-noise ratios and frequency spectra. The rectified and integrated moving average activity of the HG nerve had a peak value of 1.74 +/- 0.21 microV and a baseline value of 0.72 +/- 0.11 microV at elevated respiratory drive induced by increases in CO2 or oxygen deprivation when recorded with 10-mm-long cuffs. The frequency content of the HG electroneurogram extended from several hundred hertz to 6 kHz. Spiral nerve cuff recordings without desheathing of the nerve provided large enough signal-to-noise ratios that allowed them to be used as a measure of respiratory output and had much wider frequency bandwidths than the hook electrode preparations. A major advantage of the cuff electrode over the hook electrode was its mechanical stability, which significantly improved the reproducibility of the recordings both in terms of signal amplitudes and frequency contents.

Amplifiers, Electronic↗

PubMed1997

Interaction between tetanus long-term potentiation and hypoxia-induced potentiation in the rat hippocampus.

Interaction between tetanus long-term potentiation and hypoxia-induced potentiation in the rat hippocampus. J. Neurophysiol. 78: 2475-2482, 1997. The interaction between tetanus-induced long-term potentiation (LTP) and hypoxia-induced potentiation was investigated by performing extracellular recordings in the CA1 region of rat hippocampus using a two-pathway design. Hippocampal slices were placed in an interface chamber containing artificial cerebrospinal fluid (ACSF) solution with high magnesium concentration. Hypoxia was induced by replacing the 5% CO2-95% O2 gas mixture with 5% CO2-95% N2 for 2 min. Tetanus-LTP was induced with 1-s, 100-Hz current pulses. Significant hypoxia-induced potentiation of the slope of the dendritic excitatory postsynaptic potential (EPSP) was found in ACSF containing 2 mM of magnesium 2, 27 +/- 10% (mean +/- SE; n = 16; P < 0.01) with no change in the mean amplitude of the presynaptic volley. All experiments in which a stable control baseline was obtained were used for data analysis. The data show that short episodes (2 min) of hypoxia can induce LTP of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated synaptic transmission. The present study demonstrated that after tetanus-LTP, 33 +/- 3% (n = 10; P < 0.01), hypoxia further potentiated the field EPSP slopes by a mean value of 16 +/- 5% (n = 10; P < 0.05). Moreover, using a two-pathway design, we showed that hypoxia produced similar potentiation in both the control [19 +/- 5%; n = 10; P < 0.01) and tetanus-induced LTP pathway, and the total potentiation produced by a combination of tetanus then hypoxia, 63 +/- 13% (n = 10; p < 0.01), was significantly larger (P < 0.01) than hypoxia alone. These data suggest that hypoxia-induced potentiation is additive with tetanus-LTP. Occlusion experiments were performed to verify whether the mechanisms responsible for hypoxia-induced potentiation are independent of preexisting synaptic levels induced by high-frequency stimulation. Hypoxia produced significant potentiation (23 +/- 7%; n = 7; P < 0.05) after successful occlusion of the LTP pathway. Therefore, because the magnitude of hypoxia-induced potentiation is both independent of preexisting synaptic levels and also additive, synaptic specificity associated with LTP is preserved. The magnitude of tetanus-LTP induced 20 min after hypoxia (15 +/- 4%; n = 10) was significantly smaller (P < 0.01) relative to LTP after normoxic conditions (33 +/- 3%; n = 10). Additionally, hypoxia blocked the transient, robust potentiation occurring during the early phase of LTP induction. This study suggests that although hypoxia modifies neuronal processing by general excitation, synaptic specificity associated with tetanus-LTP still is preserved. However, hypoxia can disrupt neuronal processing by inhibiting new modification of synaptic transmission.

Animals↗

PubMed1996

A generalized cable equation for magnetic stimulation of axons.

During magnetic stimulation, electric fields are induced both on the inside (intracellular region) and the outside (extracellular region) of nerve fibers. The induced electric fields in each region can be expressed as the sum of a primary and a secondary component. The primary component arises due to an applied time varying magnetic field and is the time derivative of a vector potential. The secondary component of the induced field arises due to charge separation in the volume conductor surrounding the nerve fiber and is the gradient of a scalar potential. The question, "What components of intracellular fields and extracellular induced electric fields contribute to excitation?" has, so far, not been clearly addressed. In this paper, we address this question while deriving a generalized cable equation for magnetic stimulation and explicitly identify the different components of applied fields that contribute to excitation. In the course of this derivation, we review several assumptions of the core-conductor cable model in the context of magnetic stimulation. It is shown that out of the possible four components, only the first spatial derivative of the intracellular primary component and the extracellular secondary component of the fields contribute to excitation of a nerve fiber. An earlier form of the cable equation for magnetic stimulation has been shown to result in solutions identical to three-dimensional (3-D) volume-conductor model for the specific configuration of an isolated axon in a located in an infinite homogenous conducting medium. In this paper, we extend and generalize this result by demonstrating that our generalized cable equation results in solutions identical to 3-D volume conductor models even for complex geometries of volume conductors surrounding axons such as a nerve bundle of different conductivity surrounding axons. This equivalence in the solutions is valid for several representations of a nerve bundle such as anisotropic monodomain and bidomain models.

Animals↗

PubMed1995

Analysis of magnetic stimulation of a concentric axon in a nerve bundle.

In this paper, we present an analysis of magnetic stimulation of an axon located at the center of a nerve bundle. A three-dimensional axisymmetric volume conductor model is used to determine the transmembrane potential response along an axon due to induced electric fields produced by a toroidal coil. We evaluate four such models of an axon located in: 1) an isotropic nerve bundle with no perineurium, 2) an anisotropic nerve bundle without a perineurium, 3) an isotropic nerve bundle surrounded by a perineurium, and 4) an anisotropic nerve bundle surrounded by a perineurium. The transmembrane polarization computed along an axon for the above four models is compared to that for an axon located in an infinite homogeneous medium. These calculations indicate that a nerve bundle with no sheath has little effect on the transmembrane potential. However, the presence of a perinerium around the nerve bundle and anisotropy in the bundle significantly affects the shape of the transmembrane response. Therefore, during magnetic stimulation, nerve bundle anisotropy and the presence of perineurium must be taken into account for calculation of stimulus intensities for threshold excitation.

Animals↗

PubMed1994

Desynchronization of epileptiform activity by extracellular current pulses in rat hippocampal slices.

1. A single cathodic current pulse applied in the somatic CA1 region of the hippocampus was found to induce a large decrease in the amplitude of the population spike. 2. Intracellular recordings showed intense cellular firing suggesting the amplitude decrease could not be attributed to a decrease in neuronal firing. 3. Simultaneous intracellular and extracellular potentials were recorded to analyse the synchronization of neuronal firing in the CA1 region. Action potentials were synchronized with the first population spike but this synchronization decreased with subsequent spikes. Histograms of the phase of the action potentials displayed a normal distribution. 4. Histograms of the phases of the action potentials following the application of the 'singular stimulus' (one producing a singular response) revealed a uniform distribution of the phases suggesting that the neuronal population was desynchronized. 5. This desynchronization effect of the singular stimulus was verified by double intracellular recordings. The simultaneous firing of two neurons could be desynchronized by the application of the singular stimulus. 6. These findings indicate that it is possible to desynchronize a neuronal pool with the application of a single current pulse. In addition, the results show that it is possible for a neuronal population to fire a large number of action potentials with no resulting evoked potentials in the extracellular space.

Action Potentials↗

PubMed1994

Nonlinear parameter estimation by linear association: application to a five-parameter passive neuron model.

Linear associative memories (LAM) have been intensely used in the areas of pattern recognition and parallel processing for the past two decades. Application of LAM to nonlinear parameter estimation, however, has only been recently attempted. The process consists in converting the nonlinear function in the parameters into a set of linear algebraic equations. The nature of the linearized system and the factors influencing the accuracy of the parameter estimates have not yet been fully investigated. In this paper, LAM is applied to a nonlinear five-parameter model of the neuron. Ill-conditioning, which is often exhibited in LAM, is treated with the method of regularization as well as by the singular value decomposition (SVD). Simulation results indicate that the parameters estimated by LAM exhibit a remarkable robustness against additive white noise in comparison with the classical gradient optimization technique. Moreover, it is shown that regularization can be superior to SVD under certain conditions. Our results suggest that LAM can be used both as a noise reduction technique and as a stand-alone nonlinear parameter estimation algorithm. The comparison between LAM and a gradient technique show that, for this estimation problem, the LAM method can give more reliable estimates. Further improvements in estimation quality may still be achieved by the use of other forms of regularizing functions.

Linear Models↗

PubMed1994

Reconstruction of hippocampal CA1 pyramidal cell electrophysiology by computer simulation.

1. We have developed a 16-compartment model that reproduces most of the features of the CA1 pyramidal cell electrophysiology observed experimentally. The model was constructed using seven active ionic conductances: gNa, gCa, gDR, gCT, gA, gM, and gAHP whose kinetics have been, inferred, in most cases, from the available voltage-clamp data obtained from these cells. We focussed the simulation on the initial and late accommodation, the slow depolarization potential and the spike broadening during repetitive firing, because their mechanisms are not well understood. 2. Current-clamp records were reproduced by iterative adjustments to the ionic maximum conductances, scaling and/or "reshaping" of the gates' time constant within the experimental voltage-clamp data, and shifting the position of the steady-state gate opening. The final properties of the ionic channels were not significantly different from the voltage-clamp experiments. 3. The resulting model reproduces all four after-potentials that have been recorded to follow activation of the cell. The fast, medium, and slow after-hyperpolarization potentials (AHPs) were, respectively, generated by ICT, IM, and IAHP. Furthermore, the model suggests that the mechanisms underlying the depolarization after potential (DAP) is mostly due to passive recharging of the soma by the dendrites. 4. The model also reproduces most of the firing features experimentally observed during injection of long current pulses. Model responses showed a small initial decrease in the firing frequency during a slow underlying depolarization potential, followed by a more significant frequency decrease. Moreover, a gradual broadening of the action potential and loss of the fast AHP were also observed during the initial high-frequency firing, followed, as the firing frequency decreased, by a gradual recovery of the spikes' original width and fast AHP amplitude increase. 5. A large reduction of the K repolarizing current was required to reproduce the spike broadening and reduction of the fast AHP experimentally observed in CA1 cells during repetitive firing responses. The incorporation of a transient Ca- and voltage-dependent K current (ICT) into the model successfully reproduced these experimental observations. In contrast, we were unable to reproduce this phenomenon when a large persistent Ca- and voltage-dependent K current (generally named IC) was included in the model. These results suggest that there is a strong contribution to action-potential repolarization and fast AHP by a transient Ca- and voltage-dependent K current (ICT). 6. The two accommodation steps were induced by a progressively enlargement of two K currents IM (initial) and IAHP (late).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗