The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform
Alain Destexhe - One of the best experts on this subject based on the ideXlab platform.
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Estimation of synaptic conductances and their variances from intracellular recordings of neocortical neurons in vivo
Neurocomputing, 2020Co-Authors: Michael Rudolph, Denis Paré, J. Guillaume Pelletier, Alain DestexheAbstract:During intense network activity, neocortical neurons are in a "High-Conductance" State. To estimate the respective contributions of excitatory and inhibitory conductances in generating such States, we combined computational models with intracellular recordings obtained in cat parietal cortex in vivo. Fitting a fluctuating-conductance model to the recordings revealed that inhibitory conductances are dominant (several times larger than excitation). Conductance variance (i.e., the "noise") was also larger for inhibition, indicating that inhibitory dynamics have a pronounced impact on membrane potential fluctuations. We conclude that the synaptic bombardment of neocortical neurons in vivo is not excitatory, but mostly determined by inhibitory conductances
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Location independence and fast conduction of synaptic inputs in neocortical neurons in vivo
Neurocomputing, 2020Co-Authors: Alain Destexhe, Michael RudolphAbstract:Neocortical neurons in vivo operate in a High-Conductance State characterized by an intense intracellular fluctuating activity. Here we investigate how these conditions impact on the dendritic integration of synaptic inputs by using biophysical models of morphologically reconstructed neocortical pyramidal neurons. We find that the combined effect of high conductance and fluctuating activity due to the synaptic background activity may set pyramidal neurons into an integrative mode which is determined by the intensity of network activity, which is fast-conducting and in which the impact of inputs is roughly location-independent
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High discharge variability in neurons driven by current noise
Neurocomputing, 2020Co-Authors: Mathilde Badoual, Zuzanna Piwkowska, Michael Rudolph, Alain DestexheAbstract:Cortical neurons in vivo show a highly irregular spontaneous discharge activity, characterized by a gamma statistics and coefficient of variation around unity. Modelling studies showed that this irregularity is a consequence of the High-Conductance State caused by the ongoing activity in the cortical network. Here, we investigate to which extent this high discharge variability can be reproduced in vitro using current noise injection. In agreement with numerical studies, we found that equalizing the time constant of the noisy input with the membrane time constant may lead to an irregular discharge activity which, however, departs from a gamma statistics
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Event-based simulation strategy for conductance-based synaptic interactions and plasticity
Neurocomputing, 2020Co-Authors: Michelle Rudolph, Alain DestexheAbstract:The immense computational and adaptive power of the cerebral cortex emerges from the collective dynamics of large populations of interacting neurons. Thus, for theoretical investigations, optimal strategies for modeling biophysically faithful neuronal dynamics are required. Here, we propose an extension of the classical leaky integrate-and-fire neuronal model, the gIF model. It incorporates various aspects of High-Conductance State dynamics typically seen in cortical neurons in vivo, as well as activity-dependent modulation of synaptic weights. The analytic description of the resulting neuronal models allows their use together with the event-driven simulation strategy. The latter provides an efficient tool for exact simulations of large-scale neuronal networks
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Point-conductance models of cortical neurons with high discharge variability
Neurocomputing, 2020Co-Authors: Michael Rudolph, Alain DestexheAbstract:Recent in vivo intracellular measurements indicate that cortical neurons operate in a High-Conductance State mainly caused by intense network activity. Biophysical models of morphologically-reconstructed neocortical neurons with thousands of random synaptic events successfully reproduce intracellular measurements and the high discharge variability. Here we compare several classes of simplified models. Experimental findings are reproduced when the High-Conductance component is explicitly taken into account. In contrast to integrate-and-fire models, the high discharge variability does not depend on the balance between excitation and inhibition. We suggest that basic electrophysiological properties and irregular activity of cortical neurons in vivo can be optimally captured by High-Conductance models
Jeanpierre Mazat - One of the best experts on this subject based on the ideXlab platform.
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from calcium signaling to cell death two conformations for the mitochondrial permeability transition pore switching from low to high conductance State
Biochimica et Biophysica Acta, 1998Co-Authors: Francois Ichas, Jeanpierre MazatAbstract:The permeability transition pore (PTP) is a channel of the inner mitochondrial membrane that appears to operate at the crossroads of two distinct physiological pathways, i.e., the Ca2+ signaling network during the life of the cell, and the effector phase of the apoptotic cascade during Ca2+-dependent cell death. Correspondingly, two open conformations of the PTP can also be observed in isolated organelles. A low-conductance State, that allows the diffusion of small ions like Ca2+, is pH-operated, promoting spontaneous closure of the channel. A High-Conductance State, that allows the unselective diffusion of big molecules, stabilizes the channel in the open conformation, disrupting in turn the mitochondrial structure and causing the release of proapoptotic factors. Our current results indicate that switching from low- to High-Conductance State is an irreversible process that is strictly dependent on the saturation of the internal Ca2+-binding sites of the PTP. Thus, the High-Conductance State of the PTP, which was shown to play a pivotal role in the course of excitotoxic and thapsigargin-induced cell death, might result from a Ca2+-dependent conformational shift of the low-conductance State, normally participating in the regulation of cellular Ca2+ homeostasis as a pH-operated channel. These observations lead us to propose a simple biophysical model of the transition between Ca2+ signaling and Ca2+-dependent apoptosis.
Yuzhi Chen - One of the best experts on this subject based on the ideXlab platform.
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sensory stimulation shifts visual cortex from synchronous to asynchronous States
Nature, 2014Co-Authors: Yuzhi Chen, Benjamin Scholl, Eyal Seidemann, Nicholas J PriebeAbstract:Intracellular recordings distinguish between mechanisms that can account for variability in primary visual cortex of alert primates, consistent with a scheme in which spiking is driven by infrequent synchronous events during fixation, with sensory stimulation shifting the cortex to an asynchronous State. During spontaneous activity and sensory stimulation, neural responses in the mammalian cerebral cortex are highly variable. The dominant hypothesis offered to explain the phenomenon is that the cerebral cortex in alert animals is in an asynchronous High-Conductance State. Nicholas Priebe and colleagues have used whole-cell recordings to obtain direct views of the synaptic input to single neurons in the primary visual cortex of monkeys performing a fixation task and their results favour an alternative hypothesis, in which during fixation without sensory stimulation, spiking is driven by infrequent correlated events. But when visual stimuli are presented, the cortex shifts from a synchronous to an asynchronous State. This finding suggests that a common cortical circuit can shift between synchronous and asynchronous States depending on sensory drive. In the mammalian cerebral cortex, neural responses are highly variable during spontaneous activity and sensory stimulation. To explain this variability, the cortex of alert animals has been proposed to be in an asynchronous High-Conductance State in which irregular spiking arises from the convergence of large numbers of uncorrelated excitatory and inhibitory inputs onto individual neurons1,2,3,4. Signatures of this State are that a neuron’s membrane potential (Vm) hovers just below spike threshold, and its aggregate synaptic input is nearly Gaussian, arising from many uncorrelated inputs1,2,3,4. Alternatively, irregular spiking could arise from infrequent correlated input events that elicit large fluctuations in Vm (refs 5, 6). To distinguish between these hypotheses, we developed a technique to perform whole-cell Vm measurements from the cortex of behaving monkeys, focusing on primary visual cortex (V1) of monkeys performing a visual fixation task. Here we show that, contrary to the predictions of an asynchronous State, mean Vm during fixation was far from threshold (14 mV) and spiking was triggered by occasional large spontaneous fluctuations. Distributions of Vm values were skewed beyond that expected for a range of Gaussian input6,7, but were consistent with synaptic input arising from infrequent correlated events5,6. Furthermore, spontaneous fluctuations in Vm were correlated with the surrounding network activity, as reflected in simultaneously recorded nearby local field potential. Visual stimulation, however, led to responses more consistent with an asynchronous State: mean Vm approached threshold, fluctuations became more Gaussian, and correlations between single neurons and the surrounding network were disrupted. These observations show that sensory drive can shift a common cortical circuitry from a synchronous to an asynchronous State.
Ghanim Ullah - One of the best experts on this subject based on the ideXlab platform.
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the gain of function enhancement of ip3 receptor channel gating by familial alzheimer s disease linked presenilin mutants increases the open probability of mitochondrial permeability transition pore
Cell Calcium, 2016Co-Authors: Patrick Toglia, Ghanim UllahAbstract:Abstract Mutants in presenilins (PS1 or PS2) are the major cause of familial Alzheimer's disease (FAD). They affect intracellular Ca2+ homeostasis by increasing the open probability (Po) of inositol 1,4,5-trisposphate (IP3) receptor (IP3R) Ca2+ release channel located on the endoplasmic reticulum (ER) leading to exaggerated Ca2+ release into a cytoplasmic microdomain formed by neighboring cluster of a few IP3R channels and mitochondrial Ca2+ uniporter (MCU). Ca2+ concentration in the microdomain ( [ Ca 2 + ] mic ) depends on the distance between the cluster and MCU (r); the number of IP3R in the cluster releasing Ca2+ to the cytoplasm ( n IP 3 R ), and Po of IP3R. Using experimental whole-cell IP3R-mediated cytosolic Ca2+ data, in conjunction with a computational model of cell bioenergetics, a data-driven Markov chain model for IP3R gating, and a model for the dynamics of the mitochondrial permeability transition pore (PTP), we explore differences in mitochondrial Ca2+ uptake in cells expressing wild type (PS1-WT) and FAD-causing mutant (PS1-M146L) PS. We find that increased mitochondrial [ Ca 2 + ] m due to the gain-of-function enhancement of IP3R channels in the cells expressing PS1-M146L leads to the opening of PTP in high conductance State (PTPh), where the latency of opening is inversely correlated with r and proportional to n IP 3 R . Furthermore, we observe diminished inner mitochondrial membrane potential (ΔΨm), [NADH], [ Ca 2 + ] m , and [ATP] when PTP opens. Additionally, we explore how parameters such as the pH gradient, inorganic phosphate concentration, and the rate of the Na+/Ca2+-exchanger affect the latency of PTP to open in PTPh.
Michael Rudolph - One of the best experts on this subject based on the ideXlab platform.
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Estimation of synaptic conductances and their variances from intracellular recordings of neocortical neurons in vivo
Neurocomputing, 2020Co-Authors: Michael Rudolph, Denis Paré, J. Guillaume Pelletier, Alain DestexheAbstract:During intense network activity, neocortical neurons are in a "High-Conductance" State. To estimate the respective contributions of excitatory and inhibitory conductances in generating such States, we combined computational models with intracellular recordings obtained in cat parietal cortex in vivo. Fitting a fluctuating-conductance model to the recordings revealed that inhibitory conductances are dominant (several times larger than excitation). Conductance variance (i.e., the "noise") was also larger for inhibition, indicating that inhibitory dynamics have a pronounced impact on membrane potential fluctuations. We conclude that the synaptic bombardment of neocortical neurons in vivo is not excitatory, but mostly determined by inhibitory conductances
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Location independence and fast conduction of synaptic inputs in neocortical neurons in vivo
Neurocomputing, 2020Co-Authors: Alain Destexhe, Michael RudolphAbstract:Neocortical neurons in vivo operate in a High-Conductance State characterized by an intense intracellular fluctuating activity. Here we investigate how these conditions impact on the dendritic integration of synaptic inputs by using biophysical models of morphologically reconstructed neocortical pyramidal neurons. We find that the combined effect of high conductance and fluctuating activity due to the synaptic background activity may set pyramidal neurons into an integrative mode which is determined by the intensity of network activity, which is fast-conducting and in which the impact of inputs is roughly location-independent
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High discharge variability in neurons driven by current noise
Neurocomputing, 2020Co-Authors: Mathilde Badoual, Zuzanna Piwkowska, Michael Rudolph, Alain DestexheAbstract:Cortical neurons in vivo show a highly irregular spontaneous discharge activity, characterized by a gamma statistics and coefficient of variation around unity. Modelling studies showed that this irregularity is a consequence of the High-Conductance State caused by the ongoing activity in the cortical network. Here, we investigate to which extent this high discharge variability can be reproduced in vitro using current noise injection. In agreement with numerical studies, we found that equalizing the time constant of the noisy input with the membrane time constant may lead to an irregular discharge activity which, however, departs from a gamma statistics
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Point-conductance models of cortical neurons with high discharge variability
Neurocomputing, 2020Co-Authors: Michael Rudolph, Alain DestexheAbstract:Recent in vivo intracellular measurements indicate that cortical neurons operate in a High-Conductance State mainly caused by intense network activity. Biophysical models of morphologically-reconstructed neocortical neurons with thousands of random synaptic events successfully reproduce intracellular measurements and the high discharge variability. Here we compare several classes of simplified models. Experimental findings are reproduced when the High-Conductance component is explicitly taken into account. In contrast to integrate-and-fire models, the high discharge variability does not depend on the balance between excitation and inhibition. We suggest that basic electrophysiological properties and irregular activity of cortical neurons in vivo can be optimally captured by High-Conductance models
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Re-creating active States in vitro with a dynamic-clamp protocol
Neurocomputing, 2005Co-Authors: Zuzanna Piwkowska, Michael Rudolph, Mathilde Badoual, Alain DestexheAbstract:In neocortical neurons, network activity is responsible for intense synaptic inputs, which maintain the membrane in a High-Conductance State. Here, we propose a method for re-creating specific High-Conductance States intracellularly. This method makes use of the estimation of the mean and variance of excitatory and inhibitory conductances based on intracellular recordings, and of the injection of appropriate stochastic conductances in in vitro slice preparations using a dynamic-clamp protocol. The approach could be used to evaluate the modulation of neuronal responses by specific network States.