Biomedical subjects

Dominique M Durand

Publications and source records attributed to Dominique M Durand.

7 recordsLinked to original sources

PubMed2003

Local suppression of epileptiform activity by electrical stimulation in rat hippocampus in vitro.

High frequency electrical stimulation of deep brain structures (DBS) has been effective at controlling abnormal neuronal activity in Parkinson's patients and is now being applied for the treatment of pharmacologically intractable epilepsy. The mechanisms underlying the therapeutic effects of DBS are unknown. In particular, the effect of the electrical stimulation on neuronal firing remains poorly understood. Previous reports have showed that uniform electric fields with both AC (continuous sinusoidal) or DC waveforms could suppress epileptiform activity in vitro. In the present study, we tested the effects of monopolar electrode stimulation and low-duty cycle AC stimulation protocols, which more closely approximate those used clinically, on three in vitro epilepsy models. Continuous sinusoidal stimulation, 50 % duty-cycle sinusoidal stimulation, and low (1.68 %) duty-cycle pulsed stimulation (120 micros, 140 Hz) could completely suppress spontaneous low-Ca2+ epileptiform activity with average thresholds of 71.11 +/- 26.16 microA, 93.33 +/- 12.58 microA and 300 +/- 100 microA, respectively. Continuous sinusoidal stimulation could also completely suppress picrotoxin- and high-K+-induced epileptiform activity with either uniform or localized fields. The suppression generated by the monopolar electrode was localized to a region surrounding the stimulation electrode. Potassium concentration and transmembrane potential recordings showed that AC stimulation was associated with an increase in extracellular potassium concentration and neuronal depolarization block; AC stimulation efficacy was not orientation-selective. In contrast, DC stimulation blocked activity by membrane hyperpolarization and was orientation-selective, but had a lower threshold for suppression.

Animals↗

PubMed2003

Ionic mechanisms underlying spontaneous CA1 neuronal firing in Ca2+-free solution.

Hippocampal CA1 neurons exposed to zero-[Ca(2+)] solutions can generate periodic spontaneous synchronized activity in the absence of synaptic function. Experiments using hippocampal slices showed that, after exposure to zero-[Ca(2+)](0) solution, CA1 pyramidal cells depolarized 5-10 mV and started firing spontaneous action potentials. Spontaneous single neuron activity appeared in singlets or was grouped into bursts of two or three action potentials. A 16-compartment, 23-variable cable model of a CA1 pyramidal neuron was developed to study mechanisms of spontaneous neuronal bursting in a calcium-free extracellular solution. In the model, five active currents (a fast sodium current, a persistent sodium current, an A-type transient potassium current, a delayed rectifier potassium current, and a muscarinic potassium current) are included in the somatic compartment. The model simulates the spontaneous bursting behavior of neurons in calcium-free solutions. The mechanisms underlying several aspects of bursting are studied, including the generation of triplet bursts, spike duration, burst termination, after-depolarization behavior, and the prolonged inactive period between bursts. We show that the small persistent sodium current can play a key role in spontaneous CA1 activity in zero-calcium solutions. In particular, it is necessary for the generation of an after-depolarizing potential and prolongs both individual bursts and the interburst interval.

Action Potentials↗

PubMed2003

Chronic response of the rat sciatic nerve to the flat interface nerve electrode.

The chronic effects of a reshaping nerve electrode, the flat interface nerve electrode (FINE), on sciatic nerve physiology, histology, and blood-nerve barrier (BNB) are presented. The FINE electrode applies a small force to a nerve to reshape the nerve and fascicles into elongated ovals. This increases the interface between the nerve and electrode for selective stimulation and recording of peripheral nerve activity. The hypothesis of this study is that a small force applied noncircumferentially to a nerve can chronically reshape the nerve without effecting nerve physiology, histology, or the blood-nerve barrier permeability. Three FINE electrode designs were implanted on rat sciatic nerves to examine the nerve's response to small, moderate, and high reshaping forces. The chronic reshaping, physiology, and histology of the nerve were examined at 1, 7, and 28 days postimplant. All FINEs significantly reshape both the nerve and the fascicles compared to controls. FINEs that applied high forces caused a neurapraxia type injury characterized by changes in the animal's footprint, nerve histology, and the BNB permeability. The physiological changes were greatest at 7 days and fully recover to normal by 14 days postimplant. The moderate force FINE did not result in changes in the footprint or BNB permeability. Only a minor decrease in axon density without accompanying evidence of axon demyelination or regeneration was observe for the moderate force. The small force FINE does not cause any change in nerve physiology, histology, or BNB permeability compared to the sham treatment. An electrode that applies a small force that results in an estimated intrafascicular pressure of less than 30 mm Hg can reshape the nerve without significant changes in the nerve physiology or histology. These results support the conclusion that a small force chronically applied to the nerve reshapes the nerve without injury.

Animals↗

PubMed2003

Subfascicle stimulation selectivity with the flat interface nerve electrode.

The flat interface nerve electrode (FINE) is an alternative to cylindrical nerve cuffs for functional electrical stimulation (FES). By elongating the nerve in cross section, the FINE places more stimulating contacts around the nerve, and moves central axons closer to the electrode surface. Previous experiments have demonstrated that the FINE can activate selectively each fascicle in the cat sciatic nerve, and modeling studies have indicated that it should be possible to selectively activate groups of axons within individual fascicles. This hypothesis is tested using a combination of experimental and modeling techniques. Pairs of contacts stimulating the same fascicle were tested for subfascicle level selectivity, defined as the fraction of fibers activated by one contact but not by the other. It was possible to achieve greater than 90% selectivity with the FINE, but there was considerable variation in the results. The modeling studies showed that the selectivity achievable with a given contact pair depended strongly on the relative locations of the electrode and fascicle. Therefore, reshaping the cross section of a nerve can provide selectivity at the subfascicular level, but the electrode design must be optimized to improve selectivity across different nerve geometries.

Animals↗

PubMed2002

Functionally selective peripheral nerve stimulation with a flat interface nerve electrode.

One of the important goals of peripheral nerve electrode development is to design an electrode for selective recruitment of the different functions of a common nerve trunk. A challenging task is gaining selective access to central axon populations. In this paper, a simple electrode that takes advantage of the neural plasticity to reshape the nerve is presented. The flat interface nerve electrode (FINE) reshapes the nerve into a flat geometry to increase the surface area and move central axon populations close to the surface. The electrode was implanted acutely on the sciatic nerve of eight cats. The FINE can significantly reshape the nerve and fascicles (p < 0.0001) while maintaining the same total nerve cross-sectional area. The stimulation thresholds were 2.89 nC for pulse amplitude modulation and 10.2 nC for pulse-width modulation. Monopolar, square-pulse stimulation with single contacts on the FINE selectively recruited each of the four main branches of the sciatic nerve. Simultaneous stimulation with two contacts produced moments about the ankle joint that were a combination of the moments produced by the individual contacts when stimulated separately.

Anatomy, Cross-Sectional↗

PubMed2002

Conditions sufficient for nonsynaptic epileptogenesis in the CA1 region of hippocampal slices.

Nonsynaptic mechanisms exert a powerful influence on seizure threshold. It is well-established that nonsynaptic epileptiform activity can be induced in hippocampal slices by reducing extracellular Ca(2+) concentration. We show here that nonsynaptic epileptiform activity can be readily induced in vitro in normal (2 mM) Ca(2+) levels. Those conditions sufficient for nonsynaptic epileptogenesis in the CA1 region were determined by pharmacologically mimicking the effects of Ca(2+) reduction in normal Ca(2+) levels. Increasing neuronal excitability, by removing extracellular Mg(2+) and increasing extracellular K(+) (6-15 mM), induced epileptiform activity that was suppressed by postsynaptic receptor antagonists [D-(-)-2-amino-5-phosphonopentanoic acid, picrotoxin, and 6,7-dinitroquinoxaline-2,3-dione] and was therefore synaptic in nature. Similarly, epileptiform activity induced when neuronal excitability was increased in the presence of K(Ca) antagonists (verruculogen, charybdotoxin, norepinephrine, tetraethylammonium salt, and Ba(2+)) was found to be synaptic in nature. Decreases in osmolarity also failed to induce nonsynaptic epileptiform activity in the CA1 region. However, increasing neuronal excitability (by removing extracellular Mg(2+) and increasing extracellular K(+)) in the presence of Cd(2+), a nonselective Ca(2+) channel antagonist, or veratridine, a persistent sodium conductance enhancer, induced spontaneous nonsynaptic epileptiform activity in vitro. Both novel models were characterized using intracellular and ion-selective electrodes. The results of this study suggest that reducing extracellular Ca(2+) facilitates bursting by increasing neuronal excitability and inhibiting Ca(2+) influx, which might, in turn, enhance a persistent sodium conductance. Furthermore, these data show that nonsynaptic mechanisms can contribute to epileptiform activity in normal Ca(2+) levels.

Animals↗

PubMed2002

Noise and coupling affect signal detection and bursting in a simulated physiological neural network.

Signal detection in the CNS relies on a complex interaction between the numerous synaptic inputs to the detecting cells. Two effects, stochastic resonance (SR) and coherence resonance (CR) have been shown to affect signal detection in arrays of basic neuronal models. Here, an array of simulated hippocampal CA1 neurons was used to test the hypothesis that physiological noise and electrical coupling can interact to modulate signal detection in the CA1 region of the hippocampus. The array was tested using varying levels of coupling and noise with different input signals. Detection of a subthreshold signal in the network improved as the number of detecting cells increased and as coupling was increased as predicted by previous studies in SR; however, the response depended greatly on the noise characteristics present and varied from SR predictions at times. Careful evaluation of noise characteristics may be necessary to form conclusions about the role of SR in complex systems such as physiological neurons. The coupled array fired synchronous, periodic bursts when presented with noise alone. The synchrony of this firing changed as a function of noise and coupling as predicted by CR. The firing was very similar to certain models of epileptiform activity, leading to a discussion of CR as a possible simple model of epilepsy. A single neuron was unable to recruit its neighbors to a periodic signal unless the signal was very close to the synchronous bursting frequency. These findings, when viewed in comparison with physiological parameters in the hippocampus, suggest that both SR and CR can have significant effects on signal processing in vivo.

Algorithms↗