A detailed anatomical and mathematical model of the hippocampal formation for the generation of sharp-wave ripples and theta-nested gamma oscillations

International audienceThe mechanisms underlying the broad variety of oscillatory rhythms measured in the hippocampus during the sleep-wake cycle are not yet fully understood. In this article, we propose a computational model of the hippocampal formation based on a realistic topology and synaptic connectivity, and we analyze the effect of different changes on the network, namely the variation of synaptic conductances, the variations of the CAN channel conductance and the variation of inputs. By using a detailed simulation of intracerebral recordings, we show that this model is able to reproduce both the theta-nested gamma oscillations that are seen in awake brains and the sharp-wave ripple complexes measured during slow-wave sleep. The results of our simulations support the idea that the functional connectivity of the hippocampus, modulated by the sleep-wake variations in Acetylcholine concentration, is a key factor in controlling its rhythms

Towards practical application of Verticillium isaacii Vt305 to control Verticillium wilt of cauliflower : exploring complementary biocontrol strategies

Verticillium wilt is one of the most important diseases of cauliflower and can lead to serious economic losses. In this study, two complementary strategies were explored to employ the antagonistic capacity of Verticillium isaacii towards Verticillium wilt of cauliflower. The first strategy focused on introducing V. isaacii Vt305 by artificial inoculation of cauliflower plantlets at the nursery stage. Two inoculum types (spores and microsclerotia of V. isaacii Vt305) and different concentrations of microsclerotia were tested in greenhouse and field trials. Seed treatment with 500 microsclerotia seed(-1) led to a satisfying biocontrol level of Verticillium wilt. In addition, the PHYTO-DRIP(R) system was successful in delivering the microsclerotia to cauliflower seeds. The second strategy relied on the stimulation of the natural V. isaacii populations by rotating cauliflower with green manures and potato. Four green manure crops and potato were tested during multiple field experiments. Although these crops seemed to stimulate the V. isaacii soil population, this increase did not result in a control effect on Verticillium wilt of cauliflower in the short term. Importantly, our results indicate that the use of green manures is compatible with the application of V. isaacii Vt305 as biocontrol agent of Verticillium wilt in cauliflower

Hemodynamic correlates of spontaneous neural activity measured by human whole-head resting state EEG + fNIRS

The brains of awake, resting human subjects display spontaneously occurring neural activity patterns whose magnitude is typically many times greater than those triggered by cognitive or perceptual performance. Such resting state (RS) activity is thought to reflect the functional organization of the brain. In addition, both evoked and RS activation affect local cerebral hemodynamic properties through processes collectively referred to as neurovascular coupling. This is a major topic of interest due to its relationship with pathological conditions that include hypertension, stroke, subarachnoid hemorrhage, and traumatic brain injury. Its investigation calls for an ability to track both the neural and vascular aspects of brain function. We used scalp electroenc ephalography (EEG) which provided a measure of the electrical potentials generated by cortical postsynaptic currents. Simultaneously we utilized functional near-infrared spectroscopy (NIRS) to continuously monitor hemoglobin concentration changes in superficial cortical layers. The multi-modal signal from 18 healthy adult subjects allowed us to investigate the association of neural activity in a range of frequencies over the whole-head to local changes in hemoglobin concentrations. Our results verified the delayed alpha (8-16 Hz) modulation of hemodynamics in posterior areas known from the literature. They also indicated strong beta (16-32 Hz) modulation of hemodynamics. Analysis revealed, however, that beta modulation was likely generated by the alpha-beta coupling in EEG. Signals from the inferior electrode sites were dominated by scalp muscle related activity. Our study aimed to characterize the phenomena related to neurovascular coupling observable by practical, cost-effective, and non-invasive multi-modal techniques

Desirable traits of a good biocontrol agent against Verticillium wilt

The soil-borne fungus Verticillium causes serious vascular disease in a wide variety of annual crops and woody perennials. Verticillium wilt is notoriously difficult to control by conventional methods, so there is great potential for biocontrol to manage this disease. In this study we aimed to review the research about Verticillium biocontrol to get a better understanding of characteristics that are desirable in a biocontrol agent (BCA) against Verticillium wilt. We only considered studies in which the BCAs were tested on plants. Most biocontrol studies were focused on plants of the Solanaceae, Malvaceae, and Brassicaceae and within these families eggplant, cotton, and oilseed rape were the most studied crops. The list of bacterial BCAs with potential against Verticillium was dominated by endophytic Bacillus and Pseudomonas isolates, while non-pathogenic xylem-colonizing Verticillium and Fusarium isolates topped the fungal list. Predominant modes of action involved in biocontrol were inhibition of primary inoculum germination, plant growth promotion, competition and induced resistance. Many BCAs showed in vitro antibiosis and mycoparasitism but these traits were not correlated with activity in vivo and there is no evidence that they play a role in planta. Good BCAs were obtained from soils suppressive to Verticillium wilt, disease suppressive composts, and healthy plants in infested fields. Desirable characteristics in a BCA against Verticillium are the ability to (1) affect the survival or germination of microsclerotia, (2) colonize the xylem and/or cortex and compete with the pathogen for nutrients and/or space, (3) induce resistance responses in the plant and/or (4) promote plant growth. Potential BCAs should be screened in conditions that resemble the field situation to increase the chance of successful use in practice. Furthermore, issues such as large scale production, formulation, preservation conditions, shelf life, and application methods should be considered early in the process of selecting BCAs against Verticillium

From sleep spindles of natural sleep to spike and wave discharges of typical absence seizures: is the hypothesis still valid?

The temporal coincidence of sleep spindles and spike-and-wave discharges (SWDs) in patients with idiopathic generalized epilepsies, together with the transformation of spindles into SWDs following intramuscular injection of the weak GABAA receptor (GABAAR) antagonist, penicillin, in an experimental model, brought about the view that SWDs may represent ‘perverted’ sleep spindles. Over the last 20 years, this hypothesis has received considerable support, in particular by in vitro studies of thalamic oscillations following pharmacological/genetic manipulations of GABAARs. However, from a critical appraisal of the evidence in absence epilepsy patients and well-established models of absence epilepsy it emerges that SWDs can occur as frequently during wakefulness as during sleep, with their preferential occurrence in either one of these behavioural states often being patient dependent. Moreover, whereas the EEG expression of both SWDs and sleep spindles requires the integrity of the entire cortico-thalamo-cortical network, SWDs initiates in cortex while sleep spindles in thalamus. Furthermore, the hypothesis of a reduction in GABAAR function across the entire cortico-thalamo-cortical network as the basis for the transformation of sleep spindles into SWDs is no longer tenable. In fact, while a decreased GABAAR function may be present in some cortical layers and in the reticular thalamic nucleus, both phasic and tonic GABAAR inhibitions of thalamo-cortical neurons are either unchanged or increased in this epileptic phenotype. In summary, these differences between SWDs and sleep spindles question the view that the EEG hallmark of absence seizures results from a transformation of this EEG oscillation of natural sleep

Prise en charge d’une épilepsie nouvellement diagnostiquée

International audiencePoints essentiels : Le diagnostic d’une épilepsie de novo est difficile. La démarche diagnostique doit être rigoureuse et suivre les étapes clés précises. Crise épileptique ou malaise non épileptique : risque d’environ 20 % d’erreur diagnostique.Devant une première crise d’épilepsie non provoquée, connaître les facteurs de risque de récidive de crises motivant l’introduction d’un traitement antiépileptique. Optimiser le choix de la première molécule antiépileptique : elle doit être adaptée au type, à l’étiologie de l’épilepsie et au patient (métier, mode de vie, âge, sexe, comorbidités, traitements associés). Une éducation complète et précise du patient doit systématiquement accompagner la mise en place du traitement médicamenteux (conseils hygièno-diététiques, intérêt de l’ observance, caractéristiques et des effet secondaires du médicament, pronostic de la maladie, mode de suivi, contraintes de vie liées à la maladie…). Le suivi régulier est essentiel pour s’assurer de l’observance, de la tolérance et de l’efficacité du traitement, ainsi que de la bonne acceptation de la maladie. Un dépistage systématique des comorbidités fréquemment associées à la maladie épileptique devra être réalisé. L’électroencéphalogramme et le dosage des antiépileptiques ne sont pas indiqués dans le suivi des patients épileptiques connus sauf cas particuliers

EEG-fMRI study of temporal and spatial BOLD signal changes during epileptiform abnormalities

L’épilepsie est une pathologie neurologique caractérisée par une activité neuronale excessive et hypersynchrone soit localisée soit diffuse. L’activité neuronale est principalement évaluée par la mesure de l’activité électrique neuronale en électroencéphalographie (EEG). L’EEG dispose d’une excellente résolution temporelle, mais d’une résolution spatiale médiocre. L’enjeu actuel est de développer une technique non-invasive capable d’explorer et de localiser l’activité neuronale avec une bonne résolution temporo-spatiale afin d’améliorer la prise en charge de l’épilepsie. L’activité neuronale peut également être définie par des modifications hémodynamiques et métaboliques (couplage neurovasculaire). L’imagerie par résonance magnétique fonctionnelle (IRMf) mesure ces dernières au travers de l’étude du signal BOLD (Blood Oxygenation Level Dependent) et permet l’exploration de l’activité neuronale avec une bonne résolution spatiale. L’EEG-IRMf permet l’étude du signal BOLD spécifiquement lors des événements EEG. Si cette technique a démontré un certain intérêt dans la localisation des générateurs des anomalies épileptiformes intercritiques, il n’est pas rare d’observer des discordances entre les réponses observées et le foyer épileptique supposé. En effet, les résultats représentent l’activité globale cérébrale au cours de l’anomalie EEG. Dans une première partie, nous avons cherché à améliorer la spécificité des réponses BOLD observées lors des anomalies intercritiques. Pour cela nous avons exploré l’effet des fluctuations de l’état de vigilance au cours de l’enregistrement EEG-IRMf. Les variations des rythmes EEG physiologiques, reflets de la vigilance, sont responsables de fluctuations du signal BOLD significatives. L’intégration de ces données dans le modèle linéaire général diminue la variance du signal BOLD de la période contrôle. Ainsi, les réponses BOLD obtenues pour les anomalies épileptiformes devraient être améliorées et moins discordantes avec la localisation du foyer supposé. Dans une deuxième partie, nous avons souhaité étudier les crises épileptiques. L’application de la technique d’EEG-IRMf dans les crises permettrait d’obtenir des informations spatiales plus fiables que les anomalies intercritiques (meilleur rapport signal sur bruit) et cruciales dans la définition de la zone épileptogène. Sur une série de 8 patients atteints de malformation de développement cortical, nous avons démontré la faisabilité de l’enregistrement des crises épileptiques en EEG-IRMf mais également l’intérêt des informations obtenues sur les structures impliquées lors de la décharge critique. Cependant, l’analyse actuelle modélise la crise comme un événement stationnaire dans le temps et dans l’espace. Et de façon plus nette que lors de l’étude des anomalies intercritiques, les réponses BOLD obtenues pour les crises sont diffuses et reflètent l’activité globale cérébrale sans distinction claire entre la zone génératrice et la zone de propagation. Au cours d’un deuxième travail, nous avons intégré dans l’analyse statistique les informations temporelles fournies par la mesure du signal BOLD. La résolution temporelle de l’IRMf apporte un bon échantillonnage de la réponse hémodynamique et permet une analyse fiable des variations temporelles du signal BOLD. Nous avons analysé les réponses BOLD des crises de 10 patients avec leur décours temporel. Les zones impliquées dans le départ des crises ont pu être discriminées de celles impliquées secondairement dans la propagation. Dans une troisième partie, nous avons utilisé les données BOLD non plus dans un but localisateur de l’activité neuronale mais afin de définir le rôle des structures impliquées dans l’activité épileptique."Epilepsy is a neurological disorder defined by an excessive and hypersynchronous neuronal activity. This abnormal cerebral activity can be focal or diffuse. The neuronal activity is commonly determined by the neuronal electric activity explored in electroencephalography (EEG). The EEG is characterized by a high temporal resolution and a low spatial resolution. The development of a new technique that can explore and localize the neuronal activity with a good temporal and spatial resolution is real challenge in the epilepsy field. The neuronal activity may also be defined by hemodynamic and metabolic changes (neurovascular coupling). These changes can be explored by the functional magnetic resonance imaging (fMRI).The fMRI records the BOLD signal (Blood Oxygenation Level Dependent) changes and allows the study of neuronal activity with an excellent spatial resolution. The simultaneous EEG-fMRI recording provides information about BOLD changes specifically correlated in time with EEG events. It has been demonstrated that this technique could provide valuable results on the generators of epileptiform interictal events. However, EEG-fMRI studies showed also some discrepancies between the location of BOLD responses and the suspected epileptic focus. Indeed, BOLD responses reflect not only the generator’s activity but also the global cerebral activity occurring at the time of the epileptiform event. In the first part, we tried to improve the specificity of the BOLD responses observed during interictal epileptiform abnormalities. Therefore, we explored the BOLD effect of the alertness fluctuations during prolonged EEG-fMRI recording. Physiological rhythms variations reflecting the brain state changes are responsible for noteworthy BOLD changes. Physiological EEG rhythms may be integrated to the EEG-fMRI analysis in studies with fluctuation of alertness, to eliminate possible confounding factors. The accuracy of the BOLD results obtained for interictal epileptiform events would be improved. In a second part, we proposed to use the EEG-fMRI technique to study epileptic seizures. This new application would provide information with a better spatial definition than the interictal study (better signal to noise ratio) and crucial for the definition of the epileptogenic zone in presurgical exploration. On a population of eight patients with a malformation of cortical development, we demonstrated that the EEG-fMRI recording during seizures is feasible and that the results showed original and valuable information on cerebral structures involved in the ictal discharge. However, the actual method uses a “bloc design” model and then suggests that the seizure is a stationary event in time and in space. With this method, BOLD responses obtained during ictal event are diffuse and reflect the cerebral global activity without discrimination between the seizure onset zone and the structures secondary involved in the propagation. In a second work, we proposed a new method adding in the statistical analysis the temporal information provided by the BOLD signal measurement. The temporal resolution of fMRI and the temporal sampling used in fMRI protocol are sufficient to study with a good accuracy the temporal variations of the BOLD signal. We analyzed the dynamic time course of the BOLD signal in ten patients with seizures inside the MRI

Etude structurale et fonctionnelle du cluster eps de Streptococcus thermophilus IP6756 : spécificités et hypothèses nouvelles

The S. thermophilus IP6756 eps cluster organization is very original. On the one hand in that EPS-producing strain only two ORF compose the regulation module instead of four for other eps cluster of this specie and on the other hand, only two ORF form the biosynthesis-export module. Interestingly, none of those ORF products display glycosyltransferase enzyme homology. Functional study of this cluster shows that it is organized in operon and that its polar interruption does not lead to any modification in EPS yield. All these results indicate that the S. thermophilus IP6756 eps cluster is not involved in EPS production (on quantitative terms) and that EPS production is under control of gene(s) elsewhere in the genome, particularly glycosyltransferases genes. Like other S. thermophilus eps clusters, the genome of the IP6756 strain displays orf14.9, whose function is unknown. This ORF is transcribed. After disruption experiments, no links can be established between this ORF function and EPS production, at least on quantitative term. Nevertheless, orf14.9 integrity seems to be necessary to an optimal growth of S. thermophilus.L'organisation du cluster eps de S. thermophilus IP6756 est très particulière. Ainsi, chez cette souche productrice d'EPS, le module de régulation n'est constitué que de deux des quatre ORF présentes dans les autres clusters eps de l'espèce. De même, le module de biosynthèse et d'export n'est constitué que de deux ORF. Enfin, les produits potentiels de ces ORF ne présentent aucune homologie avec des glycosyltransférases. Sur le plan fonctionnel, le cluster eps de cette souche présente une organisation opéronique. Son interruption s'accompagne du maintien de la production d'EPS. Un ou plusieurs gènes extérieurs au cluster eps seraient donc nécessaires à la biosynthèse des EPS de la souche IP6756, notamment ceux codant les glycosyltransférases nécessaires. Comme les autres clusters eps de S. thermophilus, le cluster eps de la souche IP6756 contient orf14.9 dont la fonction est inconnue et qui est transcrite. Les expériences d'interruption réalisées n'ont pas permis d'établir un lien entre la fonctionnalité de cette ORF et la production d'EPS, au moins sur un plan quantitatif. Par contre, il semble que l'intégrité de cette ORF soit nécessaire à une croissance optimale de S. thermophilus