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N T Carnevale

Publications and source records attributed to N T Carnevale.

11 recordsLinked to original sources
PubMed1992

Kinetics of diffusion in a spherical cell. I. No solute buffering.

Realistic neuron models that involve effects of concentration changes of second messengers on ion channels must include processes such as diffusion and solute buffering. These processes, which span a wide range of spatial and temporal scales, may impose a severe computational burden. In this paper and its companion, we examine the kinetics of diffusion and present methods for stimulating it accurately and efficiency. The problem of calcium diffusion in a spherical cell is used as a device to demonstrate the practical application of our analysis. However, the scope of these papers is not limited to this problem. The same analysis that we apply and concerns that we raise are germane to the spread of any second messenger, and can be adapted to other geometries. The focus of this paper is the simplest case: diffusion in the absence of solute buffering. This analysis also applies whenever buffering is so fast that it is instantaneous compared to diffusion, or so slow that concentration gradients have dissipated before substantial buffering takes place. The second paper investigates the more difficult situation where diffusion and buffering occur at comparable rates. In the absence of buffering, concentration changes produced by diffusion can be fit by an infinite series of exponential terms. We show how to design a model with N + 1 compartments that fits the N slowest terms of this series exactly in a shell just inside the cell membrane.

Animals↗
PubMed1992

Kinetics of diffusion in a spherical cell. II. Solute buffering included.

This paper on diffusion kinetics in neurons presents an analysis of diffusion in the presence of solute buffering. Computational rather than theoretical methods are usually necessary since buffering generally precludes an analytical solution to the diffusion equations. As in the companion paper, our methods are illustrated in the context of calcium diffusion in a spherical cell. However, the same methods can be applied to the spread of any second messenger and other geometries. Analytical or computational predictions of the time course of diffusion and buffering may help guide further experiments and simulations. For example, simulations of calcium diffusion in a model of the bullfrog sympathetic ganglion cell show that buffering at depths greater than 5-6 microns is almost instantaneous compared to diffusion from sources at the cell membrane. Since buffering complicates the design of multicompartmental models, we demonstrate that a few compartments designed on the basis of diffusion alone (Carnevale and Rosenthal, 1992) may be a satisfactory framework for a model that includes bimolecular buffering. An analytical solution may be possible if the buffering reaction can be linearized. We describe a method for linearizing bimolecular saturating buffering, i.e., approximating it by a unimolecular non-saturating process that immobilizes solute. The analytical solution for the linearized reactive diffusion problem fits a non-linear model of calcium movement in the bullfrog sympathetic ganglion cell quite well after a few milliseconds.

Animals↗
PubMed1990

Neuron simulations with SABER.

Computational models can provide critical tests of hypotheses of neuronal function. These models are essential for dealing with the complications of time- and voltage-dependent (active) ionic conductances. Commercial circuit analysis programs have been useful tools for this work. We report our experience modelling biophysically realistic membrane properties with SABER (Analogy, Inc.), a new general purpose simulator. SABER allows construction of models with arbitrary membrane properties. This is a major advantage over similar programs (e.g. SPICE), which are limited to a predefined library of electronic components. The empirically determined equations that describe rate constants, ionic conductances, currents, and concentration shifts can be translated directly into model elements ('templates') written in C-like code. We describe the development of SABER models that simulate a synapse and an action potential.

Action Potentials↗
PubMed1987

Numerical analysis of electrotonus in multicompartmental neuron models.

Advances in anatomical and biophysical techniques have produced a wealth of data from certain classes of mammalian central neurons. In order to evaluate quantitatively these data and the hypotheses of neuronal function to which they lead, we have developed LADDER, a computer program for simulating neuronal electrotonus under current- or voltage-clamp conditions. This program models a neuron as an unbranched series of isopotential compartments composed of resistive and capacitive elements, i.e., a ladder network. Synaptic inputs are represented by realistic time-varying conductance changes. LADDER solves the set of simultaneous linear differential equations that describe this model by numerical integration in the time domain. Several tests confirmed the accuracy of LADDER's calculations. Simulated responses to current pulses were quantitatively similar to the charging transients that have been reported in hippocampal CA3 pyramidal neurons. These digital simulations also agreed closely with previously reported results from an analog neuronal model. In addition, transfer of synaptic charge in the model neuron, under both current- and voltage-clamp conditions, equalled theoretical predictions from two-port analyses of linear electrotonus. To illustrate the application of LADDER, we present the results of simulations involving the spread of voltage and current arising from various synaptic inputs.

Computer Simulation↗
PubMed1986

Integration of data obtained at fixed intervals.

This article discusses the design and implementation of a program well suited to integrating experimental or simulated data obtained at fixed intervals. The program uses Simpson's method and produces substantially better accuracy than trapezoidal rule integration at little extra computational cost. It accepts command line specification of integration parameters (step size and/or number) and source files. Multiple source files and integration parameters can be specified at runtime. Output can be displayed on the console or redirected to an ASCII file.

Computers↗
PubMed1984

Digitizing graphic data.

Using a digitizing pad instead of a ruler and calipers accelerates and increases the accuracy of graphic data analysis. Factors important in choosing and using such a pad are discussed in this article. A program is presented which facilitates use of the Houston Instruments HiPad DT11, a digitizing pad which is particularly well suited to neurophysiological applications.

Computers↗
PubMed1980

Two reciprocating current components underlying slow oscillations in Aplysia bursting neurons.

The mechanisms of the slow oscillatory potential in burst firing neurons in the abdominal ganglion of Aplysia californica (L3-L6 and R15) were studied using voltage clamp methods, including a novel tract and hold technique. The steady-state negative resistance characteristic (NRC) of these neurons is attributed to the activation of a moderately fast, persistent, inward current over a range of membrane potential below spike threshold. This inward current is quite sensitive to changes in external sodium concentration (Na)0 and insensitive to potassium (K)0. By contrast, the portion of the I-V curve below the NRC range is insensitive to (Na)0, but highly sensitive to (K)0. The results of 'track and store' voltage clamping show that there are actually two reciprocating currents whose combined action produces the slow oscillation. In addition to the inward current, there is a slow outward current which develops during the depolarized (burst) phase. The slow outward current can also be evoked, and more completely examined, with prolonged depolarizing voltage commands. The extremely slow decay of this current (tau approximately 45 sec) appears to be the factor underlying the slow, ramplike depolarization of Vm during the interburst interval. This slow outward current is insensitive to changes of (Na)0, but changes with (K)0 in a manner consistent with the Nerst equation. We conclude that the burst-inducing slow oscillations are generated as follows: a moderately fast inward sodium dependent current (INa) produces a regenerative depolarization, and this in turn, produces a much slower outward potassium current (IS) which hyperpolarizes the cell. The cycle is completed when IS has decayed sufficiently to allow Vm to depolarize enough to reactivate INa. We have used a quantitative version of this model to determine the time courses of gNa and gK throughout the oscillation, and to explain why different portions of the oscillatory cycle display 'graded' or 'all-or-none' behavior.

Animals↗
PubMed1980

Amphotericin B-induced myelopathy.

Two patients with coccidioidal meningitis experienced transient neurologic deficits shortly after receiving intrathecal injections of amphotericin B. Continuation of treatment eventually led to a severe flaccid paraparesis with a thoracic sensory level in one patient, and a partial Brown-Séquard's syndrome in the other. Myelography was normal in both, with no evidence of arachnoiditis. Autopsy findings in the first patient showed a focal area of necrosis in the left half of the spinal cord consistent with the patient's clinical findings during life. The distribution of the lesion corresponded to the area supplied by a central sulcal artery. Amphotericin B may exert a direct toxic effect on the spinal cord or its vascular supply when given intrathecally.

Amphotericin B↗