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Accueil du site > Equipes de recherche > Equipe CMO (N.Ravel, N.Buonviso) > Annuaire > Pages personnelles > Nicolas FOURCAUD-TROCME



par Nicolas Fourcaud-Trocme - 13 mars 2013

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  • Briffaud V, Fourcaud-Trocmé N, Messaoudi B, Buonviso N, Amat C. The relationship between respiration-related membrane potential slow oscillations and discharge patterns in mitral/tufted cells: what are the rules? PloS one. 7(8):e43964.
    Résumé : BACKGROUND: A slow respiration-related rhythm strongly shapes the activity of the olfactory bulb. This rhythm appears as a slow oscillation that is detectable in the membrane potential, the respiration-related spike discharge of the mitral/tufted cells and the bulbar local field potential. Here, we investigated the rules that govern the manifestation of membrane potential slow oscillations (MPSOs) and respiration-related discharge activities under various afferent input conditions and cellular excitability states. METHODOLOGY AND PRINCIPAL FINDINGS: We recorded the intracellular membrane potential signals in the mitral/tufted cells of freely breathing anesthetized rats. We first demonstrated the existence of multiple types of MPSOs, which were influenced by odor stimulation and discharge activity patterns. Complementary studies using changes in the intracellular excitability state and a computational model of the mitral cell demonstrated that slow oscillations in the mitral/tufted cell membrane potential were also modulated by the intracellular excitability state, whereas the respiration-related spike activity primarily reflected the afferent input. Based on our data regarding MPSOs and spike patterns, we found that cells exhibiting an unsynchronized discharge pattern never exhibited an MPSO. In contrast, cells with a respiration-synchronized discharge pattern always exhibited an MPSO. In addition, we demonstrated that the association between spike patterns and MPSO types appeared complex. CONCLUSION: We propose that both the intracellular excitability state and input strength underlie specific MPSOs, which, in turn, constrain the types of spike patterns exhibited.
    Mots-clés : Animals, Intracellular Space, Kinetics, Male, Membrane Potentials, Odors, Olfactory Bulb, Periodicity, Rats, Rats, Wistar, Respiration.
  • Brunel N, Chance FS, Fourcaud N, Abbott LF. Effects of synaptic noise and filtering on the frequency response of spiking neurons. Physical review letters. 86(10):2186-2189.
    Résumé : Noise can have a significant impact on the response dynamics of a nonlinear system. For neurons, the primary source of noise comes from background synaptic input activity. If this is approximated as white noise, the amplitude of the modulation of the firing rate in response to an input current oscillating at frequency omega decreases as 1/square root[omega] and lags the input by 45 degrees in phase. However, if filtering due to realistic synaptic dynamics is included, the firing rate is modulated by a finite amount even in the limit omega-->infinity and the phase lag is eliminated. Thus, through its effect on noise inputs, realistic synaptic dynamics can ensure unlagged neuronal responses to high-frequency inputs.
    Mots-clés : Action Potentials, Mathematical Computing, Models, Neurological, Neurons, Synapses, Synaptic Transmission.

  • Courtiol E, Hegoburu C, Litaudon P, Garcia S, Fourcaud-Trocmé N, Buonviso N. Individual and synergistic effects of sniffing frequency and flow rate on olfactory bulb activity. Journal of neurophysiology. 106(6):2813-2824.
    Résumé : Is faster or stronger sniffing important for the olfactory system? Odorant molecules are captured by sniffing. The features of sniffing constrain both the temporality and intensity of the input to the olfactory structures. In this context, it is clear that variations in both the sniff frequency and flow rate have a major impact on the activation of olfactory structures. However, the question of how frequency and flow rate individually or synergistically impact bulbar output has not been answered. We have addressed this question using multiple experimental approaches. In double-tracheotomized, anesthetized rats, we recorded both the bulbar local field potential (LFP) and mitral/tufted cells' activities when the sampling flow rate and frequency were controlled independently. We found that a tradeoff between the sampling frequency and the flow rate could maintain olfactory bulb sampling-related rhythmicity and that only an increase in flow rate could induce a faster, odor-evoked response. LFP and sniffing were recorded in awake rats. We found that sampling-related rhythmicity was maintained during high-frequency sniffing. Furthermore, we observed that the covariation between the frequency and flow rate, which was necessary for the tradeoff seen in the anesthetized preparations, also occurred in awake animals. Our study shows that the sampling frequency and flow rate can act either independently or synergistically on bulbar output to shape the neuronal message. The system likely takes advantage of this flexibility to adapt sniffing strategies to animal behavior. Our study provides additional support for the idea that sniffing and olfaction function in an integrated manner.
    Mots-clés : Action Potentials, Analysis of Variance, Anesthesia, Animals, Biological Clocks, Male, Odors, Olfactory Bulb, Olfactory Pathways, Rats, Rats, Wistar, Reaction Time, Respiration, Sensory Receptor Cells, Smell, Telemetry, Tracheotomy, Wakefulness.

  • David FO, Hugues E, Cenier T, Fourcaud-Trocmé N, Buonviso N. Specific entrainment of mitral cells during gamma oscillation in the rat olfactory bulb. PLoS computational biology. 5(10):e1000551.
    Résumé : Local field potential (LFP) oscillations are often accompanied by synchronization of activity within a widespread cerebral area. Thus, the LFP and neuronal coherence appear to be the result of a common mechanism that underlies neuronal assembly formation. We used the olfactory bulb as a model to investigate: (1) the extent to which unitary dynamics and LFP oscillations can be correlated and (2) the precision with which a model of the hypothesized underlying mechanisms can accurately explain the experimental data. For this purpose, we analyzed simultaneous recordings of mitral cell (MC) activity and LFPs in anesthetized and freely breathing rats in response to odorant stimulation. Spike trains were found to be phase-locked to the gamma oscillation at specific firing rates and to form odor-specific temporal patterns. The use of a conductance-based MC model driven by an approximately balanced excitatory-inhibitory input conductance and a relatively small inhibitory conductance that oscillated at the gamma frequency allowed us to provide one explanation of the experimental data via a mode-locking mechanism. This work sheds light on the way network and intrinsic MC properties participate in the locking of MCs to the gamma oscillation in a realistic physiological context and may result in a particular time-locked assembly. Finally, we discuss how a self-synchronization process with such entrainment properties can explain, under experimental conditions: (1) why the gamma bursts emerge transiently with a maximal amplitude position relative to the stimulus time course; (2) why the oscillations are prominent at a specific gamma frequency; and (3) why the oscillation amplitude depends on specific stimulus properties. We also discuss information processing and functional consequences derived from this mechanism.
    Mots-clés : Action Potentials, Animals, Male, Models, Neurological, Neurons, Odors, Olfactory Bulb, Pattern Recognition, Automated, Rats, Rats, Wistar, Respiration, Signal Processing, Computer-Assisted, Systems Biology.

  • David F, Courtiol E, Buonviso N, Fourcaud-Trocmé N. Competing mechanisms of gamma and beta oscillations in the olfactory bulb based on multimodal inhibition of mitral cells over a respiratory cycle. eneuro.:ENEURO.0018-15.2015. Available at: http://eneuro.org/content/early/2015/11/12/ENEURO.0018-15.2015.
    Résumé : Gamma (∼40-90Hz) and beta (∼15-40Hz) oscillations and their associated neuronal assemblies are key features of neuronal sensory processing. However, the mechanisms involved in either their interaction and/or the switch between these different regimes in most sensory systems remain misunderstood. Based on in vivo recordings and biophysical modeling of the mammalian olfactory bulb (OB), we propose a general scheme where OB internal dynamics can sustain two distinct dynamical states, each dominated by either a gamma or a beta regime. The occurrence of each regime depends on the excitability level of granule cells, the main OB interneurons. Using this model framework, we demonstrate how the balance between sensory and centrifugal input can control the switch between the two oscillatory dynamical states. In parallel, we experimentally observed that sensory and centrifugal inputs to the rat OB could be both modulated by the animal respiration (2-12Hz) and phase-shifted one with each other. Implementing this phase shift in our model resulted in the appearance of the alternation between gamma and beta rhythms within a single respiratory cycle, as in our experimental results under urethane anesthesia. Our theoretical framework can also account for the oscillatory frequency response depending on the odor intensity, the odor valence and the animal sniffing strategy observed under various conditions including freely-moving. Importantly, the results of the present model can form a basis to understand how fast rhythms could be controlled by the slower sensory and centrifugal modulations linked to the respiration. Significance Statement: Neuronal oscillations accompany the sensory perception at multiple timescales. Fast paced activities (gamma (∼40-90Hz) or beta (∼15-40Hz)) facilitate discrimination and signal cognitive response. Slower processes (2-12Hz) gate the time window for sensory and centrifugal inputs to ascend and descend, respectively, relative to sensory relays. In the olfactory bulb which is the first relay of the olfactory system, the main local interneurons provide a major interface between ascending and descending activities. The balance between these two pathways controls the two types of inhibition released by these interneurons on the main relay cells and thereby the network oscillatory dynamics. Using minimalist computational simulations and in vivo experiments, we proposed a general scheme intimately linked to olfactory processing.
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  • Duménieu M, Fourcaud-Trocmé N, Garcia S, Kuczewski N. Afterhyperpolarization (AHP) regulates the frequency and timing of action potentials in the mitral cells of the olfactory bulb: role of olfactory experience. Physiological Reports. 3(5):e12344. Available at: http://physreports.physiology.org/content/3/5/e12344.
    Résumé : Afterhyperpolarization (AHP) is a principal feedback mechanism in the control of the frequency and patterning of neuronal firing. In principal projection neurons of the olfactory bulb, the mitral cells (MCs), the AHP is produced by three separate components: classical potassium‐mediated hyperpolarization, and the excitatory and inhibitory components, which are generated by the recurrent dendrodendritic synaptic transmission. Precise spike timing is involved in olfactory coding and learning, as well as in the appearance of population oscillatory activity. However, the contribution of the AHP and its components to these processes remains unknown. In this study, we demonstrate that the AHP is developed with the MC firing frequency and is dominated by the potassium component. We also show that recurrent synaptic transmission significantly modifies MC AHP and that the strength of the hyperpolarization produced by the AHP in the few milliseconds preceding the action potential (AP) emission determines MC firing frequency and AP timing. Moreover, we show that the AHP area is larger in younger animals, possibly owing to increased Ca2+ influx during MC firing. Finally, we show that olfactory experience selectively reduces the early component of the MC AHP (under 25 msec), thus producing a modification of the AP timing limited to the higher firing frequency. On the basis of these results, we propose that the AHP, and its susceptibility to be selectively modulated by the recurrent synaptic transmission and olfactory experience, participate in odor coding and learning by modifying the frequency and pattern of MC firing.

  • Fourcaud N, Brunel N. Dynamics of the firing probability of noisy integrate-and-fire neurons. Neural computation. 14(9):2057-2110.
    Résumé : Cortical neurons in vivo undergo a continuous bombardment due to synaptic activity, which acts as a major source of noise. Here, we investigate the effects of the noise filtering by synapses with various levels of realism on integrate-and-fire neuron dynamics. The noise input is modeled by white (for instantaneous synapses) or colored (for synapses with a finite relaxation time) noise. Analytical results for the modulation of firing probability in response to an oscillatory input current are obtained by expanding a Fokker-Planck equation for small parameters of the problem - when both the amplitude of the modulation is small compared to the background firing rate and the synaptic time constant is small compared to the membrane time constant. We report here the detailed calculations showing that if a synaptic decay time constant is included in the synaptic current model, the firing-rate modulation of the neuron due to an oscillatory input remains finite in the high-frequency limit with no phase lag. In addition, we characterize the low-frequency behavior and the behavior of the high-frequency limit for intermediate decay times. We also characterize the effects of introducing a rise time to the synaptic currents and the presence of several synaptic receptors with different kinetics. In both cases, we determine, using numerical simulations, an effective decay time constant that describes the neuronal response completely.
    Mots-clés : Action Potentials, Animals, Artifacts, Cerebral Cortex, Models, Neurological, Neural Pathways, Neurons, Periodicity, Probability, Synapses.

  • Fourcaud-Trocmé N, Brunel N. Dynamics of the instantaneous firing rate in response to changes in input statistics. Journal of computational neuroscience. 18(3):311-321.
    Résumé : We review and extend recent results on the instantaneous firing rate dynamics of simplified models of spiking neurons in response to noisy current inputs. It has been shown recently that the response of the instantaneous firing rate to small amplitude oscillations in the mean inputs depends in the large frequency limit f on the spike initiation dynamics. A particular simplified model, the exponential integrate-and-fire (EIF) model, has a response that decays as 1/f in the large frequency limit and describes very well the response of conductance-based models with a Hodgkin-Huxley type fast sodium current. Here, we show that the response of the EIF instantaneous firing rate also decays as 1/f in the case of an oscillation in the variance of the inputs for both white and colored noise. We then compute the initial transient response of the firing rate of the EIF model to a step change in its mean inputs and/or in the variance of its inputs. We show that in both cases the response speed is proportional to the neuron stationary firing rate and inversely proportional to a 'spike slope factor' Delta(T) that controls the sharpness of spike initiation: as 1/Delta(T) for a step change in mean inputs, and as 1/Delta(T) (2) for a step change in the variance in the inputs.
    Mots-clés : Action Potentials, Animals, Computer Simulation, Humans, Models, Neurological, Neurons, Nonlinear Dynamics.

  • Fourcaud-Trocmé N, Courtiol E, Buonviso N. Two distinct olfactory bulb sublaminar networks involved in gamma and beta oscillation generation: a CSD study in the anesthetized rat. Frontiers in Neural Circuits. 8:88.
    Résumé : A prominent feature of olfactory bulb (OB) dynamics is the expression of characteristic local field potential (LFP) rhythms, including a slow respiration-related rhythm and two fast alternating oscillatory rhythms, beta (15-30 Hz) and gamma (40-90 Hz). All of these rhythms are implicated in olfactory coding. Fast oscillatory rhythms are known to involve the mitral-granule cell loop. Although the underlying mechanisms of gamma oscillation have been studied, the origin of beta oscillation remains poorly understood. Whether these two different rhythms share the same underlying mechanism is unknown. This study uses a quantitative and detailed current-source density (CSD) analysis combined with multi-unit activity (MUA) recordings to shed light on this question in freely breathing anesthetized rats. In particular, we show that gamma oscillation generation involves mainly the upper half of the external plexiform layer (EPL) and superficial areas of granule cell layer (GRL). In contrast, the generation of beta oscillation involves the lower part of the EPL and deep granule cells. This differential involvement of sublaminar networks is neither dependent on odor quality nor on the precise frequency of the fast oscillation under study. Overall, this study demonstrates a functional sublaminar organization of the rat OB, which is supported by previous anatomical findings.

  • Fourcaud-Trocmé N, Courtiol E, Buonviso N, Voegtlin T. Stability of fast oscillations in the mammalian olfactory bulb: experiments and modeling. Journal of physiology, Paris. 105(1-3):59-70.
    Résumé : In the rat olfactory bulb (OB), fast oscillations of the local field potential (LFP) are observed during the respiratory cycle. Gamma-range oscillations (40-90 Hz) occur at the end of inspiration, followed by beta-range oscillations (15-30 Hz) during exhalation. These oscillations are highly stereotypical, and their frequencies are stable under various conditions. In this study, we investigate the effect of stimulus intensity on activity in the OB. Using a double-cannulation protocol, we showed that although the frequency of the LFP oscillation does depend on the respiratory cycle phase, it is relatively independent of the intensity of odorant stimulation. In contrast, we found that the individual firing rate of mitral OB cells dramatically changed with the intensity of the stimulation. This suggests that OB fast oscillation parameters, particularly frequency, are fully determined by intrinsic OB network parameters. To test this hypothesis, we explored a model of the OB where fast oscillations are generated by the interplay between excitatory mitral/tufted cells and inhibitory granule cells with graded inhibition. We found that our model has two distinct activity regimes depending on the amount of noise. In a low-noise regime, the model displays oscillation in the beta range with a stable frequency across a wide range of excitatory inputs. In a high-noise regime, the model displays oscillatory dynamics with irregular cell discharges and fast oscillations, similar to what is observed during gamma oscillations but without stability of the oscillation frequency with respect to the network external input. Simulations of the full model and theoretical studies of the network's linear response show that the characteristics of the low-noise regime are induced by non-linearities in the model, notably, the saturation of graded inhibition. Finally, we discuss how this model can account for the experimentally observed stability of the oscillatory regimes.
    Mots-clés : Action Potentials, Animals, Male, Models, Neurological, Neural Inhibition, Neurons, Olfactory Bulb, Olfactory Pathways, Rats, Rats, Wistar.

  • Fourcaud-Trocmé N, Gervais R, Procyk E, Reynaud E. Foreword. Mechanisms underlying our cognitive functions. Journal of physiology, Paris. 105(1-3):1.
    Mots-clés : Brain, Cognition, Humans, Models, Neurological.
  • Fourcaud-Trocmé N, Hansel D, van Vreeswijk C, Brunel N. How spike generation mechanisms determine the neuronal response to fluctuating inputs. The Journal of neuroscience: the official journal of the Society for Neuroscience. 23(37):11628-11640.
    Résumé : This study examines the ability of neurons to track temporally varying inputs, namely by investigating how the instantaneous firing rate of a neuron is modulated by a noisy input with a small sinusoidal component with frequency (f). Using numerical simulations of conductance-based neurons and analytical calculations of one-variable nonlinear integrate-and-fire neurons, we characterized the dependence of this modulation on f. For sufficiently high noise, the neuron acts as a low-pass filter. The modulation amplitude is approximately constant for frequencies up to a cutoff frequency, fc, after which it decays. The cutoff frequency increases almost linearly with the firing rate. For higher frequencies, the modulation amplitude decays as C/falpha, where the power alpha depends on the spike initiation mechanism. For conductance-based models, alpha = 1, and the prefactor C depends solely on the average firing rate and a spike "slope factor," which determines the sharpness of the spike initiation. These results are attributable to the fact that near threshold, the sodium activation variable can be approximated by an exponential function. Using this feature, we propose a simplified one-variable model, the "exponential integrate-and-fire neuron," as an approximation of a conductance-based model. We show that this model reproduces the dynamics of a simple conductance-based model extremely well. Our study shows how an intrinsic neuronal property (the characteristics of fast sodium channels) determines the speed with which neurons can track changes in input.
    Mots-clés : Action Potentials, Electric Conductivity, Kinetics, Models, Neurological, Neurons, Sodium Channels.

  • Galán RF, Fourcaud-Trocmé N, Ermentrout GB, Urban NN. Correlation-induced synchronization of oscillations in olfactory bulb neurons. The Journal of neuroscience: the official journal of the Society for Neuroscience. 26(14):3646-3655.
    Résumé : Oscillations are a common feature of odor-evoked and spontaneous activity in the olfactory system in vivo and in vitro and are thought to play an important role in information processing and memory in a variety of brain areas. Theoretical and experimental studies have described several mechanisms by which oscillations can be generated and synchronized. Here, we investigate the hypothesis that correlated noisy inputs are able to generate synchronous oscillations in olfactory bulb mitral cells in vitro. We consider several alternative mechanisms and conclude that olfactory bulb synchronous oscillations are likely to arise because of the response of uncoupled oscillating neurons to aperiodic but correlated inputs. This mechanism has been described theoretically, but we provide the first experimental evidence that such a mechanism may underlie synchronization in real neurons. In physiological experiments, we show that this mechanism can generate gamma-band oscillations in populations of olfactory bulb mitral cells. This mechanism synchronizes oscillatory firing by using shared fast fluctuations in stochastic inputs across neurons, without requiring any synaptic or electrical coupling. We discuss the properties and limitations of synchronization by this mechanism and suggest that it may underlie fast oscillations in many brain areas.
    Mots-clés : Action Potentials, Animals, Biological Clocks, Computer Simulation, Mice, Models, Neurological, Nerve Net, Neural Inhibition, Olfactory Bulb, Olfactory Receptor Neurons, Statistics as Topic.

  • Garcia S, Fourcaud-Trocmé N. OpenElectrophy: An Electrophysiological Data- and Analysis-Sharing Framework. Frontiers in neuroinformatics. 3:14.
    Résumé : Progress in experimental tools and design is allowing the acquisition of increasingly large datasets. Storage, manipulation and efficient analyses of such large amounts of data is now a primary issue. We present OpenElectrophy, an electrophysiological data- and analysis-sharing framework developed to fill this niche. It stores all experiment data and meta-data in a single central MySQL database, and provides a graphic user interface to visualize and explore the data, and a library of functions for user analysis scripting in Python. It implements multiple spike-sorting methods, and oscillation detection based on the ridge extraction methods due to Roux et al. (2007). OpenElectrophy is open source and is freely available for download at http://neuralensemble.org/trac/OpenElectrophy.

  • Kuczewski N, Fourcaud-Trocmé N, Savigner A, et al. Insulin modulates network activity in olfactory bulb slices: impact on odour processing. The Journal of physiology.
    Résumé : Odour perception closely depends on the nutritional status, in animals as in humans. Insulin, the principal anorectic hormone, appears as one of the major candidates for ensuring the link between the olfactory abilities and nutritional status, by modifying processing in the olfactory bulb (OB), one of its main central targets. The present study investigates whether and how insulin can act in OB, by evaluating insulin action on the main output neurons activities, mitral cells (MCs), in acute rat OB slices. Insulin was found to act at two OB network levels: 1) on MCs, by increasing their excitability, likely by inhibiting two voltage-gated potassium (K+) channels; 2) on interneurons by modifying the GABAergic and on glutamatergic synaptic activity impinging on MCs, mainly reducing them. Insulin was also found as altering the olfactory nerve (ON) evoked excitatory-post-synaptic currents in 60% of MCs. Insulin decreased or increased the ON evoked-responses in equal proportion and the direction of insulin effect depended on the initial neuron ON evoked firing-rate. Indeed insulin tended to decrease the high and to increase the low ON-evoked firing-rates, thereby reducing the inter-MCs response firing variability. Therefore the insulin effects on the evoked firing rates were not carried out indiscriminately in the MC population. By constructing a mathematical model, the impact of insulin complex effects on OB was assessed at population activity level. The model shows that the reduction of variability across cells could affect the MC detection and discrimination abilities, mainly by decreasing and, less frequently, increasing them, depending on odour quality. Thus, as previously proposed, this differential action of insulin on MCs across odours would allow this hormone to put the olfactory function under feeding signal control, taking into account the discerning valence of an odour as a function of the nutritional status.