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International audience; The aim of this work was to investigate the mechanisms that shape evoked electroencephalographic (EEG) and magneto-encephalographic (MEG) responses. We used a neuronally plausible model to characterise the dependency of response components on the models parameters. This generative model was a neural mass model of hierarchically arranged areas using three kinds of inter-area connections (forward, backward and lateral). We investigated how responses, at each level of a cortical hierarchy, depended on the strength of connections or coupling. Our strategy was to systematically add connections and examine the responses of each successive architecture. We did this in the context of deterministic responses and then with stochastic spontaneous activity. Our aim was to show, in a simple way, how event-related dynamics depend on extrinsic connectivity. To emphasise the importance of nonlinear interactions, we tried to disambiguate the components of event-related potentials (ERPs) or event-related fields (ERFs) that can be explained by a linear superposition of trial-specific responses and those engendered nonlinearly (e.g., by phase-resetting). Our key conclusions were; (i) when forward connections, mediating bottom-up or extrinsic inputs, are sufficiently strong, nonlinear mechanisms cause a saturation of excitatory interneuron responses. This endows the system with an inherent stability that precludes nondissipative population dynamics. (ii) The duration of evoked transients increases with the hierarchical depth or level of processing. (iii) When backward connections are added, evoked transients become more protracted, exhibiting damped oscillations. These are formally identical to late or endogenous components seen empirically. This suggests that late components are mediated by reentrant dynamics within cortical hierarchies. (iv) Bilateral connections produce similar effects to backward connections but can also mediate zero-lag phase-locking among areas. (v) Finally, with spontaneous activity, ERPs/ERFs can arise from two distinct mechanisms: For low levels of (stimulus related and ongoing) activity, the systems response conforms to a quasi-linear superposition of separable responses to the fixed and stochastic inputs. This is consistent with classical assumptions that motivate trial averaging to suppress spontaneous activity and disclose the ERP/ERF. However, when activity is sufficiently high, there are nonlinear interactions between the fixed and stochastic inputs. This interaction is expressed as a phase-resetting and represents a qualitatively different explanation for the ERP/ERF.

The generation of calcium oscillations at fertilisation and during mitosis appears to be controlled by the cell cycle machinery. For example, the calcium oscillations in oocytes and embryos occur during metaphase and terminate upon entry into interphase. Here we report the manipulation of sperm-triggered calcium oscillations by cyclin-dependent kinase (CDK) activity, the major component of maturation/ M phase promoting factor (MPF). To control the CDK activity we microinjected mRNAs encoding full-length GFP-tagged cyclin B1 or a truncated and therefore stabilised form of cyclin B1 (Δ90) into unfertilised oocytes. In the presence of full-length cyclin B1, the calcium oscillations terminate when cyclin B1 levels fall along with the concomitant fall in the associated CDK activity. In addition, when the CDK activity is elevated indefinitely with Δ90 cyclin B1, the calcium oscillations also continue indefinitely. Finally, in oocytes that contain low mitogen- activated protein (MAP) kinase activity and elevated CDK activity, the sperm-triggered calcium oscillations are again prolonged. We conclude that the CDK activity of the ascidian oocyte can be regarded as a positive regulator of sperm-triggered calcium oscillations, a finding that may apply to other oocytes that display sperm-triggered calcium oscillations at fertilisation. Furthermore, these findings may have a bearing upon the mitotic calcium signals of early embryos.

International audience; Characterizing the behavior and robustness of enzymatic networks with numerous variables and unknown parameter values is a major challenge in biology, especially when some enzymes have counter-intuitive properties or switch-like behavior between activation and inhibition. In this paper, we propose new methodological and tool-supported contributions, based on the intuitive formalism of temporal logic, to express in a rigorous manner arbitrarily complex dynamical properties. Our multi-step analysis allows efficient sampling of the parameter space in order to define feasible regions in which the model exhibits imposed or experimentally observed behaviors. In a first step, an algorithmic methodology involving sensitivity analysis is conducted to determine bifurcation thresholds for a limited number of model parameters or initial conditions. In a second step, this boundary detection is supplemented by a global robustness analysis, based on quasi-Monte Carlo approach that takes into account all model parameters. We apply this method to a well-documented enzymatic reaction network describing collagen proteolysis by matrix metalloproteinase MMP2 and membrane type 1 metalloproteinase (MT1-MMP) in the presence of tissue inhibitor of metalloproteinase TIMP2. For this model, our method provides an extended analysis and quantification of network robustness toward paradoxical TIMP2 switching activity between activation or inhibition of MMP2 production. Further implication of our approach is illustrated by demonstrating and analyzing the possible existence of oscillatory behaviors when considering an extended open configuration of the enzymatic network. Notably, we construct bifurcation diagrams that specify key parameters values controlling the co-existence of stable steady and non-steady oscillatory proteolytic dynamics.

International audience; The purpose of this study is to investigate the potential of the ensemble empirical mode decomposition (EEMD) to extract cardiogenic oscillations from inductive plethysmography signals in order to measure cardiac stroke volume. First, a simple cardio-respiratory model is used to simulate cardiac, respiratory, and cardio-respiratory signals. Second, application of empirical mode decomposition (EMD) to simulated cardio-respiratory signals demonstrates that the mode mixing phenomenon affects the extraction performance and hence also the cardiac stroke volume measurement. Stroke volume is measured as the amplitude of extracted cardiogenic oscillations, and it is compared to the stroke volume of simulated cardiac activity. Finally, we show that the EEMD leads to mode mixing removal.

The medial septum diagonal band area (MS/DB) projects to the hippocampus through the fornix/fimbria pathway and is implicated in generating hippocampal theta oscillations. The hippocampus also projects back to the MS/DB, but very little is known functionally about this input. Here, we investigated the physiological role of hippocamposeptal feedback to the MS/DB in a completein vitroseptohippocampal preparation containing the intact interconnecting fornix/fimbria pathway. We demonstrated that carbachol-induced rhythmic theta-like hippocampal oscillations recorded extracellularly were synchronized with powerful rhythmic IPSPs in whole-cell recorded MS/DB neurons. Interestingly, we found that these IPSPs evoked rebound spiking in GABAergic MS/DB neurons. In contrast, putative cholinergic and glutamatergic MS/DB neurons responded only weakly with rebound spiking and, as a result, were mostly silent during theta-like oscillations. We next determined the mechanism underlying the rebound spiking that followed the IPSPs in MS/DB GABAergic neurons using phasic electrical stimulation of the fornix/fimbria pathway. We demonstrate that the increased rebound spiking was attributable to the activation ofIhcurrent, because it was significantly reduced by low concentrations of theIhantagonist ZD7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride]. Together, these results suggest that rhythmical activity in hippocampus is transferred to the MS/DB and can preferentially phase the spiking of GABAergic MS/DB neurons because of their significant expression ofIhcurrents. Our data demonstrate that hippocamposeptal inhibition facilitates theta rhythmic discharges in MS/DB GABAergic neurons while favoring the inhibition of most ACh and glutamate neurons.

International audience; OBJECTIVES: Endothelial dysfunction is an early event and a critical step in the pathogenesis of systemic sclerosis. Accurate and sensitive tests are needed to correctly assess the degree of microvascular endothelial dysfunction. Spectral analysis of skin blood flow contains a characteristic low frequency reported to be associated with endothelial function in healthy subjects. We hypothesized that the relative amplitude of the oscillation recorded for this low frequency spectrum (0.008 to 0.021 Hz) would be less pronounced in patients with systemic sclerosis than in healthy subjects and in patients with primary Raynaud's phenomenon. PATIENTS AND METHOD: Twenty-one patients with systemic sclerosis, twenty patients with primary Raynaud phenomenon and eleven healthy subjects were enrolled. Skin perfusion was recorded at rest for 30 minutes using laser Doppler flowmetry on the pad of the left third left. Fourier transform spectral analysis was applied to obtain the mean amplitude of the cutaneous blood perfusion signal of the total spectrum from 0.008 to 1.6 Hz and the mean amplitude of each characteristic frequency in the laser Doppler flowmeter blood flow oscillations. RESULTS: The relative amplitudes of each characteristic frequency in the laser Doppler flowmeter blood flow oscillations were not statistically different in the three groups, particularly for frequency spectrum from 0.008 Hz to 0.021 Hz. CONCLUSION: Fourier transform spectral analysis of baseline cutaneous blood flow does not provide significant information. Further studies are required, perhaps using wavelet spectral analysis or stimulated conditions.

International audience; One of the challenges in analyzing neuronal activity is to correlate discrete signal, such as action potentials with a signal having a continuous waveform such as oscillating local field potentials (LFPs). Studies in several systems have shown that some aspects of information coding involve characteristics that intertwine both signals. An action potential is a fast transitory phenomenon that occurs at high frequencies whereas a LFP is a low frequency phenomenon. The study of correlations between these signals requires a good estimation of both instantaneous phase and instantaneous frequency. To extract the instantaneous phase, common techniques rely on the Hilbert transform performed on a filtered signal, which discards temporal information. Therefore, time-frequency methods are best fitted for non-stationary signals, since they preserve both time and frequency information. We propose a new algorithmic procedure that uses wavelet transform and ridge extraction for signals that contain one or more oscillatory frequencies and whose oscillatory frequencies may shift as a function of time. This procedure provides estimates of phase, frequency and temporal features. It can be automated, produces manageable amounts of data and allows human supervision. Because of such advantages, this method is particularly suitable for analyzing synchronization between LFPs and unitary events.

Electroencephalographic oscillations at 10 Hz (alpha and mu rhythms) are the most prominent rhythms observed in awake, relaxed (eye-closed) subjects. These oscillations may be considered as a marker of cortical inactivity or an index of the active inhibition of the sensory information. Different cortical sources may participate in the 10-Hz oscillation and appear to be modulated by the sensory context and functional demands. In microgravity, the marked reduction in multimodal graviceptive inputs to cortical networks participating in the representation of space could be expected to affect the 10-Hz activity. The effect of microgravity on this basic oscillation has heretofore not been studied quantitatively. Because the alpha rhythm has a functional role in the regulation of network properties of the visual areas, we hypothesised that the absence of gravity would affect its strength. Here, we report the results of an experiment conducted over the course of 3 space flights, in which we quantified the power of the 10-Hz activity in relation to the arrest reaction (i.e. in 2 distinct physiological states: eyes open and eyes closed). We observed that the power of the spontaneous 10-Hz oscillation recorded in the eyes-closed state in the parieto-occipital (alpha rhythm) and sensorimotor areas (mu rhythm) increased in the absence of gravity. The suppression coefficient during the arrest reaction and the related spectral perturbations produced by eye-opening/closure state transition also increased in on orbit. These results are discussed in terms of current theories on the source and the importance of the alpha rhythm for cognitive function., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Many methods have been proposed to extract pressure gradient maps from magnetic resonance (MR) images. They were based on the resolution of the haemodynamic model of Navier-Stokes and needed the flow acceleration to be known. Most used velocity data acquisition and computed acceleration from temporal and spatial derivatives of the velocity field. However, MR sequences have been developed in order to acquire the acceleration field directly. Here we compared direct MR measurements of acceleration field components with those calculated from MR velocity acquisitions. Two experimental phantoms were used to separately evaluate the inertial and convective components of the acceleration. Mathematical simulation of the convective phantom further explained the origin of the noise generated by the spatial and temporal derivatives of the velocity data, and the misregistration artefacts due to MR sequences. We found that direct measurement of the acceleration field generates less noise and fewer artefacts than calculation from velocity derivatives.

International audience; Adult brain networks generate a wide range of oscillations. Some of these are behaviourally relevant, whereas others occur during seizures and other pathological conditions. This raises the question of how physiological oscillations differ from pathogenic ones. In this review, this issue is discussed from a developmental standpoint. Indeed, both epileptic and physiological high-frequency oscillations (HFOs) appear progressively during maturation, and it is therefore possible to determine how this program corresponds to maturation of the neuronal populations that generate these oscillations. We review here important differences in the development of neuronal populations that might contribute to their different oscillatory properties. In particular, at an early stage, the density of glutamatergic synapses is too low for physiological HFOs but an additional drive can be provided by excitatory GABA, triggering epileptic HFOs and the cascades involved in long-lasting epileptogenic transformations. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

International audience; GABA excites immature neurons and inhibits adult ones, but whether this contributes to seizures in the developing brain is not known. We now report that in the developing, but not the adult, hippocampus, seizures beget seizures only if GABAergic synapses are functional. In the immature hippocampus, seizures generated with functional GABAergic synapses include fast oscillations that are required to transform a naive network to an epileptic one: blocking GABA receptors prevents the long-lasting sequels of seizures. In contrast, in adult neurons, full blockade of GABA(A) receptors generates epileptogenic high-frequency seizures. Therefore, purely glutamatergic seizures are not epileptogenic in the developing hippocampus. We suggest that the density of glutamatergic synapses is not sufficient for epileptogenesis in immature neurons; excitatory GABAergic synapses are required for that purpose. We suggest that the synergistic actions of GABA and NMDA receptors trigger the cascades involved in epileptogenesis in the developing hippocampus.

International audience; The analysis of heart period series is a difficult task especially under graded exercise conditions. From all the information present in these series, we are the most interested in the coupling between respiratory and cardiac systems, known as respiratory sinus arrythmia. In this paper, we show that precise patterns concerning the respiratory frequency can be extracted from the heart period series. An evolutive model is introduced in order to achieve tracking of the main respiratory-related frequencies and their time-varying amplitudes. Since respiration acts to modulate the sinus rhythm, we relate the frequencies and amplitudes to this modulation by analyzing in detail its nonlinear transformation giving the heart period signal. This analysis is performed assuming stationary conditions but also in the realistic case where the mean heart period, the amplitude, and the frequency of the respiration are time-varying. Since this paper is devoted to the theoretical and complete presentation of the method used in a physiological study published elsewhere, the capabilities of our method will be illustrated in a realistic simulated case.

International audience; Since the beginning of the 90's several lines of research have brought new insights concerning the temporal aspects of sensory processing. Initial observations showing that sensory stimuli can trigger evoked, or induced, oscillations has generated a large number of studies where, explicitly or implicitly, the large-scale rhythmic activity of thalamo-cortical neurons was viewed as a key factor to synchronize neurons responding to different dimensions of a given stimulus, and therefore to solve the so-called "binding problem" (for reviews see Eckhorn 2000, Singer 1990, 1999). This line of research contrasts with the rate coding concept which has been used over the last 40 years to describe the functional properties of neurons in sensory systems and the plasticity of sensory systems both during development and in adulthood. We review here results obtained in the thalamo-cortical auditory system. After a characterization of the oscillatory events, we determined their origins by inactivating each component of the thalamo-cortical loop. Then we compared, within the same animals, the oscillations obtained in anesthetized and unanesthetized conditions. Our data strongly suggest that to clarify the functional roles of evoked oscillations, and more generally of any aspects of temporal coding, we need to study them on awake animals.

International audience; In Genetic Absence Epilepsy Rats from Strasbourg (GAERS), generalized spike-and-wave (SW) discharges (5-9 SW s(-1)) develop during quiet immobile wakefulness from a natural, medium-voltage, 5-9 Hz rhythm. This study examines the spatio-temporal dynamics of cellular interactions in the somatosensory thalamocortical system underlying the generation of normal and epileptic 5-9 Hz oscillations. Paired single-unit and multi-unit recordings between the principal elements of this circuit and intracellular recordings of thalamic, relay and reticular, neurones were conducted in neuroleptanalgesied GAERS and control, non-epileptic, rats. The identity of the recorded neurones was established following juxtacellular or intracellular marking. At least six major findings have emerged from this study. (1) In GAERS, generalized spike-and-wave discharges were correlated with synchronous rhythmic firings in related thalamic relay and reticular neurones. (2) Usually, corticothalamic discharges phase-led related relay and reticular firings. (3) A depolarizing wave emerging from a barrage of EPSPs was the cause of both relay and reticular discharges. (4) In some relay cells, which had a relatively high membrane input resistance, the depolarizing wave had the shape of a ramp, which could trigger a low-threshold Ca2+ spike. (5) In reticular cells, the EPSP barrage could further trigger voltage-dependent depolarizations. (6) The epilepsy-related thalamic, relay and reticular, intracellular activities were similar to the normal-related thalamic activities. Overall, these findings strongly suggest that, during absence seizures, corticothalamic neurones play a primary role in the synchronized excitation of thalamic relay and reticular neurones. The present study further suggests that absence-related spike-and-wave discharges correspond to hypersynchronous wake-related physiological oscillations.

International audience; Tone-evoked oscillations were studied from simultaneous recordings collected in the auditory cortex, auditory thalamus and auditory sector of the reticular nucleus in urethane anesthetized rats. These oscillations were precisely time-locked to tone onset and were easily observed on peristimulus time histograms (PSTHs). Visual inspection of PSTHs and rasters led us to distinguish between 'reliable' oscillations (which exhibited oscillatory patterns in more than 50% of the trials) and 'labile' oscillations (which exhibited oscillations in less than 50% of the trials). Systematic quantification of oscillations based on several indices derived from power spectra confirmed this distinction. 'Reliable' stimulus-locked oscillations were observed in 51/184 (28%) of the recordings from auditory cortex, 9/55 (17%) of the recordings from auditory thalamus and 11/26 (42%) of the recordings from the auditory sector of the reticular nucleus. The frequency range of these oscillations was the same in the three structures (5-14 Hz). Within the same animal, when one electrode exhibited oscillations, there was a high probability of detecting similar oscillations from electrodes located in the same structure, but not from electrodes located in the other structures. These oscillations were observed for pure tone frequency (or for clicks) whatever the tone duration (1 s, 100 ms, 10 ms). The inter-tone interval (ITI) was found to be the critical factor controlling the occurrence of these oscillations: they were present for ITIs of 2 s or longer, but were absent for ITIs of 1 s or less. In contrast, the occurrence of the oscillations was a function neither of the strength of the 'on' evoked response nor of the animal's temperature. However, lowering the animal's temperature from 37-38 degrees C to 35-36 degrees C systematically led to a decrease in the frequency and an increase in the duration of the tone-evoked oscillations. These results suggest that, even in well defined conditions (temperature, EEG, ITI, level of anesthesia), the oscillations triggered by presentation of the same stimulus can be stable or unstable. This temporal instability of stimulus-evoked oscillations has to be taken into account before stating percentages of oscillations in a given brain structure. They also suggest that some general factors such as the animals temperature or the inter-stimulus interval can considerably affect their characteristics and/or their occurrence.

Rhythmic patterns of neuronal activity have been found at multiple levels of various sensory systems. In the olfactory bulb or the antennal lobe, oscillatory activity exhibits a broad range of frequencies and has been proposed to encode sensory information. However, the neural mechanisms underlying these oscillations are unknown. Bulbar oscillations might be an emergent network property arising from neuronal interactions and/or resulting from intrinsic oscillations in individual neurons. Here we show that mitral cells (output neurons of the olfactory bulb) display subthreshold oscillations of their membrane potential. These oscillations are mediated by tetrodotoxin-sensitive sodium currents and range in frequency from 10 to 50 Hz as a function of resting membrane potential. Because the voltage dependency of oscillation frequency was found to be similar to that for action potential generation, we studied how subthreshold oscillations could influence the timing of action potentials elicited by synaptic inputs. Indeed, we found that subthreshold oscillatory activity can trigger the precise occurrence of action potentials generated in response to EPSPs. Furthermore, IPSPs were found to set the phase of subthreshold oscillations and can lead to “rebound” spikes with a constant latency.Because intrinsic oscillations of membrane potential enable very precise temporal control of neuronal firing, we propose that these oscillations provide an effective means to synchronize mitral cell subpopulations during the processing of olfactory information.

Motivation: The rational design of biological networks with prescribed functions is limited to gene circuits of a few genes. Larger networks involve complex interactions with many parameters and the use of automated computational tools can be very valuable. We propose a new tool to design transcriptional networks with targeted behavior that could be used to better understand the design principles of genetic circuits.Results: We have implemented a Simulated Annealing optimization algorithm that explores throughout the space of transcription networks to obtain a specific behavior. The software outputs a transcriptional network with all the corresponding kinetic parameters in SBML format. We provide examples of transcriptional circuits with logical and oscillatory behaviors. Our tool can also be applied to design networks with multiple external input and output genes.Availability: The software, a tutorial manual, parameter sets and examples are freely available at http://synth-bio.yi.org/genetdes.htmlContact: Alfonso.Jaramillo@polytechnique.edu

The purpose of this study was to examine whether an over-stimulation of the vestibular system, induced by thousands of time saccadic head stimulations, affects the vestibular sensitivity, and consequently if such a phenomenon could contribute to the deterioration of postural stability observed after a long distance running exercise. Eighteen athletic subjects performed a 20.5 km over ground race with an average speed of 15 km.h − 1 , corresponding roughly to 7,500 strides shocks with associated saccadic accelerations transmitted to the head. A preliminary validation of the exercise protocol was realized to confirm the effect of the sustained exercise on body balance by recording standard postural parameters. A visually perceived eye level (VPEL) task was used to indirectly assess otolithic sensitivity motionless or undergoing low centrifugation conditions, before and after exercise. Results obtained from body balance analysis confirmed a decreased postural stability illustrated by increased postural oscillations after the 20.5 km run. Under low centrifugation conditions, results showed a lowering of the VPEL with the increase of the gravito-inertial acceleration in accordance with the literature. However, no significant change in the VPEL after a sustained running exercise was observed. In conclusion, the vestibular sensitivity at the otolithic level does not seem to be altered by an intensive running exercise and then failed to play a key role in the post-exercise deterioration of postural stability.