Neurocentre Magendie


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Doctorat Neurosciences, 1994, Bordeaux.
Label 'Doctor Communitatis Europeae'
Licence Maitrise Psychologie; DEA Neurosciences 1990.
DEA Psychologie, 1995, Bordeaux

Expertise: Cognition, Connectivité, Modélisation, Comportement, Mémoire spatiale, Statistiques

"C'est par l'approche du cerveau dans sa globalité que l'on pourra comprendre comment il génère la cognition" : c'est l'hypothèse motrice de mes travaux de recherche.
Dans le cadre de l'étude de la physiopathologie de la mémoire déclarative, cette hypothèse générale conduit à chercher comment l'interaction entre structures cérébrales permet l'expression de cette forme de mémoire, et notamment de la flexibilité qui la caractérise.
On peut faire appel à moi pour la modélisation de la connectivité inter-structures (modèles d'équations structurales, connectivité fonctionnelle...), l'approche multivariée des données, les tests d'hypothèses statistiques non usuelles (savoir-faire en bootstrap),... mais également l'analyse comportementale des processus cognitifs, la modélisation par réseaux de neurones formels.


Mon approche scientifique est développée ici :

Mes cours et mon approche pédagogique sont consultables ici :

9 publication(s) depuis Novembre 2007:

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* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en

21/03/2016 | Psychoneuroendocrinology   IF 4.2
Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.
Al Abed AS, Sellami A, Brayda-Bruno L, Lamothe V, Nogues X, Potier M, Bennetau-Pelissero C, Marighetto A

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as 'where I parked' requires abilities to organize/update memories to prevent proactive interference from similar memories of previous 'parking events'. Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1muM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population.

31/01/2013 | Neurobiol Dis   IF 4.9
Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent measures of brain connectivity without overt memory deficits.
Brayda-Bruno L, Mons N, Yee B K, Micheau J, Abrous DN, Nogues X, Marighetto A

The functional relevance of septo-hippocampal cholinergic (SHC) degeneration to the degradation of hippocampus-dependent declarative memory (DM) in aging and Alzheimer's disease (AD) remains ill-defined. Specifically, selective SHC lesions often fail to induce overt memory impairments in animal models. In spite of apparent normal performance, however, neuronal activity within relevant brain structures might be altered by SHC disruption. We hypothesized that partial SHC degeneration may contribute to functional alterations within memory circuits occurring in aging before DM decline. In young adult mice, we studied the effects of behaviorally ineffective (saporin-induced) SHC lesions - similar in extent to that seen in aged animals - on activity patterns and functional connectivity between three main neural memory systems: the septo-hippocampal system, the striatum and the amygdala that sustain declarative, procedural and emotional memory, respectively. Animals were trained in a radial maze procedure dissociating the human equivalents of relational/DM and non-R/DM expressions in animals. Test-induced Fos activation pattern revealed that the partial SHC lesion significantly altered the brain's functional activities and connectivity (co-activation pattern) despite the absence of overt behavioral deficit. Specifically, hippocampal CA3 hyperactivity and abnormal septo-hippocampo-amygdalar inter-connectivity resemble those observed in aging and prodromal AD. Hence, SHC neurons critically coordinate hippocampal function in concert with extra-hippocampal structures in accordance with specific mnemonic demand. Although partial SHC degeneration is not sufficient to impact DM performance by itself, the connectivity change might predispose the emergence of subsequent DM loss when, due to additional age-related insults, the brain can no longer compensate the holistic imbalance caused by cholinergic loss.

01/12/2012 | Food Chem   IF 4.1
Bioavailability of glycitein relatively to other soy isoflavones in healthy young Caucasian men.
Shinkaruk S, Durand M, Lamothe V, Carpaye A, Martinet A, Chantre P, Vergne S, Nogues X, Moore N, Bennetau-Pelissero C

Glycitein is a Selective Estradiol Receptor Modulator (SERM) from soy. The study reports plasma bioavailability and urine excretion of glycitein compared to other soy isoflavones after a unique intake of food supplement based on soy germ containing 55.24mg isoflavones. Eighteen plasma and urinary sampling profiles collected over 48h from healthy young Caucasian men were analysed using specific ELISAs. Eight profiles contained equol. Glycitein T(max), C(max), AUC(0-->24h) and T((1/2)) in plasma were calculated. Urine T(max), % of excretion at 24h and clearance were assessed. Glycitein is one of the best absorbed flavonoids. Plasma steady-state level can be achieved by several intakes a day. Glycitein bioavailability is similar to that of daidzein and its urinary excretion is significantly higher than that of genistein. Equol does not affect glycitein bioavailability. Knowing glycitein bioavailability in man is essential for the development of soy-germ-based food supplements for health applications.

14/02/2012 | Behav Brain Res   IF 3
Functions for adult neurogenesis in memory: an introduction to the neurocomputational approach and to its contribution.
Nogues X, Corsini MM, Marighetto A, Abrous DN

Until recently, it was believed that the introduction of new neurons in neuronal networks was incompatible with memory function. Since the rediscovery of adult hippocampal neurogenesis, behavioral data demonstrate that adult neurogenesis is required for memory processing. We examine neurocomputational studies to identify which basic mechanisms involved in memory might be mediated by adult neurogenesis. Mainly, adult neurogenesis might be involved in the reduction of catastrophic interference and in a time-related pattern separation function. Artificial neuronal networks suggest that the selective recruitment of new-born or old neurons is not stochastic, but depends on environmental requirements. This leads us to propose the novel concept of 'soft-supervision'. Soft-supervision would be a biologically plausible process, by which the environment is able to influence activation and learning rules of neurons differentially.

17/03/2011 | Behav Brain Res   IF 3
Detection of age-dependent working memory deterioration in APP751SL mice.
Blanchard J, Martel G, Brayda-Bruno L, Nogues X, Micheau J

Despite huge advances on Alzheimer's disease (AD) etiology, the clinical diagnosis remains the unique commonly used tool to detect the onset of the disease. For instance, epidemiological studies report that the combination of episodic and working memory disorders represents the most consistent sign of progression from mild cognitive impairment to AD. However, such working memory disorders failed to be observed early in transgenic mouse models of AD because the behavioral procedures used do not tackle properly crucial components of working memory. The aim of the present work was to assess early occurrence of working memory impairments in APP(751SL) mice. Therefore, we designed a new behavioral task in the water-maze, based on the principle of a delayed matching to place task, where spatial recognition was assessed for four different platform locations within a single session. First, we showed that dorsal hippocampal but not medial prefrontal cortex lesions in C57Bl6 mice induced a time-dependent impairment of spatial recognition. Then, the hippocampal-like memory alterations were reproduced in 7-8-month-old APP(751SL) mice but not in younger animals (5-6-month-old). We also demonstrated that these working memory deficits are related to progressive Abeta accumulation in the hippocampus, but not in the other selected brain structures.

01/12/2009 | Behav Brain Res   IF 3
Activating a memory system focuses connectivity toward its central structure.
Boucard A, Mons N, Micheau J, Nogues X

This report investigates in what way functional connectivity may explain how two memory systems that share almost all their structures, can function as separate systems. The first series of experiments was aimed at demonstrating the reliability of our experimental design by showing that acquisition of the spatial version of a water cross-maze task (stimulus-stimulus associations) was impaired by dorsal hippocampal lesions whereas the cue version (stimulus-reinforcement association) was altered by amygdala lesion. Then, we evaluated how these two tasks induce different patterns of connectivity. The connectivity was evaluated by calculating the correlations between the zif-268 immunoreactivity of 22 structures composing the hippocampus and the amygdala systems. We designed a new statistical procedure to demonstrate double dissociations on the basis of brain regional intercorrelations. Our data show that the correlations between the hippocampus and the other structures of the memory system are higher in the place-learning group compared to the cue-learning group, whereas they are enhanced with the amygdala in the latter group compared to the former. This demonstrates that the activation of a memory system consists in the focusing of functional connectivity toward the central structure of the system. This may explain how several memory systems can share the same structures while remaining independent.

Current transgenic mouse models of Alzheimer disease constitute a relevant tool to examine the relationships between neuropathological lesions, neurodegeneration and clinical syndromes. Nevertheless, addressing the relation between Abeta deposition and cognition deterioration requires careful adjustment for age to decipher underlying mechanisms of impairments and identify potential therapeutic targets. In the present work we have carried out a detailed behavioral analysis of the APP(751SL) transgenic mouse model testing 6 age-points (from 2 to 19-20 months) and estimating in parallel the cerebral Abeta deposition. The immunohistochemistry study indicated a fast progression of Abeta(17-24) staining in several brain structures that reached for most of them, a maximal level at 7-8 months of age. Behavioral experiments showed that APP(751SL) mice displayed alterations in some general functions (muscular strength, motor activity) whereas other functions are preserved (anxiety, exploration). Acquisition and extinction of an appetitive operant conditioning were used to assess early learning deficits. Hippocampal but not dorso-lateral striatal lesion was shown to delay extinction. Although some learning deficits were detected at 5-6 months in the acquisition of the operant conditioning task, more robust impairments in extinction were observed in 7-8-month-old mice. Indeed, spatial memory deficit was associated to a selective hippocampal CA1 impairment of learning-induced Zif268 activation. Because this mouse model displayed gradual memory deficits it gives the opportunity to investigate the temporal progression of molecular and cellular mechanisms that induce cognitive decline.

07/2008 | Neurobiol Aging   IF 5.2
Impairment of spatial memory consolidation in APP(751SL) mice results in cue-guided response.
Blanchard J, Martel G, Guillou JL, Nogues X, Micheau J

APP(751SL) mice of 5-6- and 7-8-month-old and their wild-type littermates were submitted to one-session learning in a water-maze with three levels of training (4, 12 or 22 trials). Training consisted in finding a submerged platform with a fixed location and marked by a cue. During testing two platforms were presented: one consistent with the spatial location allowing place-response (PR) and the other signaled by the cue enabling cued-response (CR). When testing occurred 24h after training, wild-type and 5-6-month-old APP(751SL) mice exhibited a shift in response strategy as a function of training level, by executing CR when trained with 4 trials and PR when trained with 12 trials, but 7-8-month-old APP(751SL) mice executed only CR. However, they displayed PR when tested 1h after 12- and 22-trial, suggesting a consolidation deficit. Zif268 imaging showed plasticity impairment of the hippocampal-dependent memory system but not of the dorsolateral caudate nucleus. Moreover, in these APP(751SL) mice, the deficit selectively affecting hippocampal function cannot be directly related to the onset of beta-amyloid deposits.

30/11/2007 | J Neurosci Methods   IF 2.3
Reliability and validity of structural equation modeling applied to neuroimaging data: a simulation study.
Boucard A, Marchand A, Nogues X

Structural equation modeling aims at quantifying the strength of causal relationships within a set of interacting variables. Although the literature emphasizes that large sample sizes are required, this method is increasingly used with neuroimaging data of a limited number of subjects to study the relationships between cerebral structures. Here, we use a simulation approach to evaluate its ability to provide accurate information under the constraints of neuroimaging. Artificial samples representing the activity of a virtual set of structures were generated under both recursive and non-recursive connectivity models. Structural equation modeling was performed on these samples, and the quality of the analyses was evaluated by directly comparing the estimated path coefficients with the original ones. The validity and the reliability are shown to decrease with sample size, but the estimated models respect the relative strength of path coefficients in a large percentage of cases. The 'smoothing method' appears to be the most appropriate to prevent improper solutions. Both the experimental error and the external structures influencing the network have a weak influence. Accordingly, structural equation modeling can be applied to neuroimaging data, but confidence intervals should be presented together with the path coefficient estimation.