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Alain Destexhe

Publications and source records attributed to Alain Destexhe.

44 records · Page 3Linked to original sources

Extracting synaptic conductances from single membrane potential traces

In awake animals, the activity of the cerebral cortex is highly complex, with neurons firing irregularly with apparent Poisson statistics. One way to characterize this complexity is to take advantage of the high interconnectivity of cerebral cortex and use intracellular recordings of cortical neurons, which contain information about the activity of thousands of other cortical neurons. Identifying the membrane potential (Vm) to a stochastic process enables the extraction of important statistical signatures of this complex synaptic activity. Typically, one estimates the total synaptic conductances (excitatory and inhibitory) but this type of estimation requires at least two Vm levels and therefore cannot be applied to single Vm traces. We propose here a method to extract excitatory and inhibitory conductances (mean and variance) from single Vm traces. This "VmT method" estimates conductance parameters using maximum likelihood criteria, under the assumption are that synaptic conductances are described by Gaussian stochastic processes and are integrated by a passive leaky membrane. The method is illustrated using models and is tested on guinea-pig visual cortex neurons in vitro using dynamic-clamp experiments. The VmT method holds promises for extracting conductances from single-trial measurements, which has a high potential for in vivo applications.

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Macroscopic models of local field potentials and the apparent 1/f noise in brain activity

The power spectrum of local field potentials (LFPs) has been reported to scale as the inverse of the frequency, but the origin of this "1/f noise" is at present unclear. Macroscopic measurements in cortical tissue demonstrated that electric conductivity (as well as permittivity) is frequency dependent, while other measurements failed to evidence any dependence on frequency. In the present paper, we propose a model of the genesis of LFPs which accounts for the above data and contradictions. Starting from first principles (Maxwell equations), we introduce a macroscopic formalism in which macroscopic measurements are naturally incorporated, and also examine different physical causes for the frequency dependence. We suggest that ionic diffusion primes over electric field effects, and is responsible for the frequency dependence. This explains the contradictory observations, and also reproduces the 1/f power spectral structure of LFPs, as well as more complex frequency scaling. Finally, we suggest a measurement method to reveal the frequency dependence of current propagation in biological tissue, and which could be used to directly test the predictions of the present formalism.

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Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation

Cortical neurons are subject to sustained and irregular synaptic activity which causes important fluctuations of the membrane potential (Vm). We review here different methods to characterize this activity and its impact on spike generation. The simplified, fluctuating point-conductance model of synaptic activity provides the starting point of a variety of methods for the analysis of intracellular Vm recordings. In this model, the synaptic excitatory and inhibitory conductances are described by Gaussian-distributed stochastic variables, or colored conductance noise. The matching of experimentally recorded Vm distributions to an invertible theoretical expression derived from the model allows the extraction of parameters characterizing the synaptic conductance distributions. This analysis can be complemented by the matching of experimental Vm power spectral densities (PSDs) to a theoretical template, even though the unexpected scaling properties of experimental PSDs limit the precision of this latter approach. Building on this stochastic characterization of synaptic activity, we also propose methods to qualitatively and quantitatively evaluate spike-triggered averages of synaptic time-courses preceding spikes. This analysis points to an essential role for synaptic conductance variance in determining spike times. The presented methods are evaluated using controlled conductance injection in cortical neurons in vitro with the dynamic-clamp technique. We review their applications to the analysis of in vivo intracellular recordings in cat association cortex, which suggest a predominant role for inhibition in determining both sub- and supra-threshold dynamics of cortical neurons embedded in active networks.

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A modified cable formalism for modeling neuronal membranes at high frequencies

Intracellular recordings of cortical neurons in vivo display intense subthreshold membrane potential (Vm) activity. The power spectral density (PSD) of the Vm displays a power-law structure at high frequencies (>50 Hz) with a slope of about -2.5. This type of frequency scaling cannot be accounted for by traditional models, as either single-compartment models or models based on reconstructed cell morphologies display a frequency scaling with a slope close to -4. This slope is due to the fact that the membrane resistance is "short-circuited" by the capacitance for high frequencies, a situation which may not be realistic. Here, we integrate non-ideal capacitors in cable equations to reflect the fact that the capacitance cannot be charged instantaneously. We show that the resulting "non-ideal" cable model can be solved analytically using Fourier transforms. Numerical simulations using a ball-and-stick model yield membrane potential activity with similar frequency scaling as in the experiments. We also discuss the consequences of using non-ideal capacitors on other cellular properties such as the transmission of high frequencies, which is boosted in non-ideal cables, or voltage attenuation in dendrites. These results suggest that cable equations based on non-ideal capacitors should be used to capture the behavior of neuronal membranes at high frequencies.

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Calculating event-triggered average synaptic conductances from the membrane potential

The optimal patterns of synaptic conductances for spike generation in central neurons is a subject of considerable interest. Ideally, such conductance time courses should be extracted from membrane potential (Vm) activity, but this is difficult because the nonlinear contribution of conductances to the Vm renders their estimation from the membrane equation extremely sensitive. We outline here a solution to this problem based on a discretization of the time axis. This procedure can extract the time course of excitatory and inhibitory conductances solely from the analysis of Vm activity. We test this method by calculating spike-triggered averages of synaptic conductances using numerical simulations of the integrate-and-fire model subject to colored conductance noise. The procedure was also tested successfully in biological cortical neurons using conductance noise injected with dynamic-clamp. This method should allow the extraction of synaptic conductances from Vm recordings in vivo.

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Does the 1/f frequency-scaling of brain signals reflect self-organized critical states?

Many complex systems display self-organized critical states characterized by 1/f frequency scaling of power spectra. Global variables such as the electroencephalogram, scale as 1/f, which could be the sign of self-organized critical states in neuronal activity. By analyzing simultaneous recordings of global and neuronal activities, we confirm the 1/f scaling of global variables for selected frequency bands, but show that neuronal activity is not consistent with critical states. We propose a model of 1/f scaling which does not rely on critical states, and which is testable experimentally.

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On the use of analytic expressions for the voltage distribution to analyze intracellular recordings

Different analytic expressions for the membrane potential distribution of membranes subject to synaptic noise have been proposed, and can be very helpful to analyze experimental data. However, all of these expressions are either approximations or limit cases, and it is not clear how they compare, and which expression should be used in a given situation. In this note, we provide a comparison of the different approximations available, with an aim to delineate which expression is most suitable for analyzing experimental data.

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Modeling extracellular field potentials and the frequency-filtering properties of extracellular space

Extracellular local field potentials (LFP) are usually modeled as arising from a set of current sources embedded in a homogeneous extracellular medium. Although this formalism can successfully model several properties of LFPs, it does not account for their frequency-dependent attenuation with distance, a property essential to correctly model extracellular spikes. Here we derive expressions for the extracellular potential that include this frequency-dependent attenuation. We first show that, if the extracellular conductivity is non-homogeneous, there is induction of non-homogeneous charge densities which may result in a low-pass filter. We next derive a simplified model consisting of a punctual (or spherical) current source with spherically-symmetric conductivity/permittivity gradients around the source. We analyze the effect of different radial profiles of conductivity and permittivity on the frequency-filtering behavior of this model. We show that this simple model generally displays low-pass filtering behavior, in which fast electrical events (such as Na$^+$-mediated action potentials) attenuate very steeply with distance, while slower (K$^+$-mediated) events propagate over larger distances in extracellular space, in qualitative agreement with experimental observations. This simple model can be used to obtain frequency-dependent extracellular field potentials without taking into account explicitly the complex folding of extracellular space.

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