Search PubMed⌕ Search

Biomedical subjects

A Destexhe

Publications and source records attributed to A Destexhe.

48 records · Page 3Linked to original sources
PubMed1994

Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism.

Markov kinetic models were used to synthesize a complete description of synaptic transmission, including opening of voltage-dependent channels in the presynaptic terminal, release of neurotransmitter, gating of postsynaptic receptors, and activation of second-messenger systems. These kinetic schemes provide a more general framework for modeling ion channels than the Hodgkin-Huxley formalism, supporting a continuous spectrum of descriptions ranging from the very simple and computationally efficient to the highly complex and biophysically precise. Examples are given of simple kinetic schemes based on fits to experimental data that capture the essential properties of voltage-gated, synaptic and neuromodulatory currents. The Markov formalism allows the dynamics of ionic currents to be considered naturally in the larger context of biochemical signal transduction. This framework can facilitate the integration of a wide range of experimental data and promote consistent theoretical analysis of neural mechanisms from molecular interactions to network computations.

Animals↗
PubMed1994

A model of spindle rhythmicity in the isolated thalamic reticular nucleus.

1. The oscillatory properties of the isolated reticular (RE) thalamus were modeled with the use of compartmental models of RE cells. Hodgkin-Huxley type kinetic models of ionic channels were derived from voltage- and current-clamp data from RE cells. Interactions between interconnected RE cells were simulated with the use of a kinetic model of gamma-aminobutyric acid (GABA) inhibitory synapses. 2. The intrinsic bursting properties of RE cells in the model were due to the presence of a low-threshold Ca2+ current and two Ca(2+)-activated currents. The properties of these model RE cells were compared with RE neurons recorded intracellularly in vivo in cats. 3. Model RE cells densely interconnected with GABAA synapses produced synchronous oscillations at a frequency close to that of spindles (7-14 Hz). Networks of RE neurons organized in a two-dimensional array with only proximal connectivity also exhibited synchronized oscillations in the spindle range. In addition, the proximally connected network showed periods of high and low synchronicity, giving rise to waxing and waning oscillations in the population of RE cells. 4. The spatiotemporal behavior of the network was investigated during waxing and waning oscillations. The waxing and waning emerged as an alternation between periods of desynchronized and synchronized activity, corresponding to periods of irregular and coherent spatial activity. During synchronized periods, the network displayed propagating coherent waves of synchronous activity that had a tendency to form spirals. 5. Networks of model RE neurons fully connected through GABAB synapses exhibited perfectly synchronous oscillations at lower frequencies (0.5-1 Hz), but two-dimensional networks with proximal GABAB connectivity failed to synchronize. 6. These simulations demonstrate that networks of model neurons that include the main intrinsic currents found in RE cells can generate waxing and waning oscillatory activity similar to the spindle rhythmicity observed in the isolated RE nucleus in vivo. The model reveals the interplay between the intrinsic rhythmic properties of RE cells and the fast synaptic interactions in organizing synchronized rhythmicity.

Afferent Pathways↗
PubMed1993

Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons.

The oscillatory properties of single thalamocortical neurons were investigated by using a Hodgkin-Huxley-like model that included Ca2+ diffusion, the low-threshold Ca2+ current (lT) and the hyperpolarization-activated inward current (lh). lh was modeled by double activation kinetics regulated by intracellular Ca2+. The model exhibited waxing and waning oscillations consisting of 1-25-s bursts of slow oscillations (3.5-4 Hz) separated by long silent periods (4-20 s). During the oscillatory phase, the entry of Ca2+ progressively shifted the activation function of lh, terminating the oscillations. A similar type of waxing and waning oscillation was also observed, in the absence of Ca2+ regulation of lh, from the combination of lT, lh, and a slow K+ current. Singular approximation showed that for both models, the activation variables of lh controlled the dynamics of thalamocortical cells. Dynamical analysis of the system in a phase plane diagram showed that waxing and waning oscillations arose when lh entrained the system alternately between stationary and oscillating branches.

Animals↗
PubMed1993

A model for 8-10 Hz spindling in interconnected thalamic relay and reticularis neurons.

We investigated a simplified model of a thalamocortical cell and a reticular thalamic cell interconnected with excitatory and inhibitory synapses, based on Hodgkin-Huxley type kinetics. The intrinsic oscillatory properties of the model cells were similar to those observed from single cells in vitro. When synaptic interactions were included, spindle oscillations were observed consisting of sequences of rhythmic oscillations at 8-10 Hz separated by silent periods of 8-40 s. The model suggests that Ca2+ regulation of lh channels may be responsible for the waxing and waning of spindles and that the reticular cell shapes the 10-Hz rhythmicity. The model also predicts that the kinetics of gamma-aminobutyric acid inhibitory postsynaptic potentials as well as the intrinsic properties of reticular cells are critical in determining the frequency of spindle rhythmicity.

Animals↗
PubMed1993

A model of the inward current Ih and its possible role in thalamocortical oscillations.

We investigated the kinetic properties of the hyperpolarization-activated inward current (Ih) of thalamocortical (TC) neurons. Recently, it was shown that this current is characterized by different time constants of activation and inactivation, which was in apparent conflict with the single-exponential time course of the current. We introduce here a model of Ih based on the cooperation of a slow and a fast activation variable and show that this kinetic scheme accounts for these apparently conflicting experimental data. We also report that following the combination of such a current with other currents seen in TC cells, one observes several types of oscillating behavior, similar to the slow oscillations and the spindle-like oscillations seen in vitro.

Animals↗
PubMed1988

Is the normal heart a periodic oscillator?

With the help of several independent methods of nonlinear dynamics, the electrocardiograms (ECG) of four normal human hearts are studied qualitatively and quantitatively. A total of 36 leads were tested. The power spectrum, the autocorrelation function, the phase portrait, the Poincaré section, the correlation dimension, the Lyapunov exponent and the Kolmogorov entropy all point to the fact that the normal heart is not a perfect oscillator. The cardiac activity stems from deterministic dynamics of chaotic nature characterized by correlation dimensions D2 ranging from 3.6 to 5.2. Two different phase spaces are constructed for the evaluation of D2: the introduction of time lags and the direct use of space vectors give similar results. It is shown that the variabilities in interbeat intervals are not random but exhibit short range correlations governed by deterministic laws. These correlations may be related to the accelerating and decelerating physiological processes. This new approach to the cardiac activity may be used in clinical diagnosis. Also they are valuable tools for the evaluation of mathematical models which describe cardiac activity in terms of evolution equations.

Electrocardiography↗
PubMed1986

Low-dimensional chaos in an instance of epilepsy.

Using a time series obtained from the electroencephalogram recording of a human epileptic seizure, we show the existence of a chaotic attractor, the latter being the direct consequence of the deterministic nature of brain activity. This result is compared with other attractors seen in normal human brain dynamics. A sudden jump is observed between the dimensionalities of these brain attractors (4.05 +/- 0.05 for deep sleep) and the very low dimensionality of the epileptic state (2.05 +/- 0.09). The evaluation of the autocorrelation function and of the largest Lyapunov exponent allows us to sharpen further the main features of underlying dynamics. Possible implications in biological and medical research are briefly discussed.

Brain↗
PubMedDate not supplied

Modelling corticothalamic feedback and the gating of the thalamus by the cerebral cortex.

Morphological studies have shown that excitatory synapses from the cortex constitute the major source of synapses in the thalamus. However, the effect of these corticothalamic synapses on the function of the thalamus is not well understood because thalamic neurones have complex intrinsic firing properties and interact through multiple types of synaptic receptors. Here we investigate these complex interactions using computational models. We show first, using models of reconstructed thalamic relay neurones, that the effect of corticothalamic synapses on relay cells can be similar to that of afferent synapses, in amplitude, kinetics and timing, although these synapses are located in different regions of the dendrites. This suggests that cortical EPSPs may complement (or predict) the afferent information. Second, using models of reconstructed thalamic reticular neurones, we show that high densities of the low-threshold Ca2+ current in dendrites can give these cells an exquisite sensitivity to cortical EPSPs, but only if their dendrites are hyperpolarized. This property has consequences at the level of thalamic circuits, where corticothalamic EPSPs evoke bursts in reticular neurones and recruit relay cells predominantly through feedforward inhibition. On the other hand, with depolarized dendrites, thalamic reticular neurones do not generate bursts and the cortical influence on relay cells is mostly excitatory. Models therefore suggest that the cortical influence can either promote or antagonize the relay of information, depending on the state of the dendrites of reticular neurones. The control of these dendrites may therefore be a determinant of attentional mechanisms. We also review the effect of corticothalamic feedback at the network level, and show how the cortical control over the thalamus is essential in co-ordinating widespread, coherent oscillations. We suggest mechanisms by which different modes of corticothalamic interaction would allow oscillations of very different spatiotemporal coherence to coexist in the thalamocortical system.

Animals↗
PubMedDate not supplied

Do neocortical pyramidal neurons display stochastic resonance?

Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity that has a significant impact on various electrophysiological properties and dendritic integration. Using detailed biophysical models of a morphologically reconstructed neocortical pyramidal neuron, in which synaptic background activity was simulated according to recent measurements in cat parietal cortex in vivo, we show that the responsiveness of the cell to additional periodic subthreshold stimuli can be significantly enhanced through mechanisms similar to stochastic resonance. We compare several paradigms leading to stochastic resonance-like behavior, such as varying the strength or the correlation in the background activity. A new type of resonance-like behavior was obtained when the correlation was varied, in which case the responsiveness is sensitive to the statistics rather than the strength of the noise. We suggest that this type of resonance may be relevant to information processing in the cerebral cortex.

Action Potentials↗
PubMedDate not supplied

Nonlinear thermodynamic models of voltage-dependent currents.

Hodgkin and Huxley provided the first quantitative description of voltage-dependent currents and adjusted their model to experimental data using empirical functions of voltage. A physically plausible formalism was proposed later by assuming that transition rates depend exponentially on a free-energy barrier, by analogy with the theory of reaction rates. It was also assumed that the free energy depends linearly on voltage. This thermodynamic formalism can accurately describe many processes, but the resulting time constants can be arbitrarily fast, which may also lead to aberrant behavior. We considered here a physically plausible solution to this problem by including nonlinear effects of the electrical field on the free energy. We show that including effects such as mechanical constraints, inherent to the structure of the ion channel protein, leads to more accurate thermodynamic models. These models can account for voltage-dependent transitions that are rate-limited in a given voltage range, without invoking additional states. We illustrate their applicability to fit experimental data by considering the case of the T-type calcium current in thalamic neurons.

Animals↗