Lyon Neuroscience Research Center

Sainte-Foy-lès-Lyon, France

Lyon Neuroscience Research Center

Sainte-Foy-lès-Lyon, France
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Ravassard P.,French Institute of Health and Medical Research | Ravassard P.,Lyon Neuroscience Research Center | Ravassard P.,University of Lyon | Ravassard P.,University of California at Los Angeles | And 9 more authors.
Neurobiology of Learning and Memory | Year: 2015

Memory consolidation is the process for long-term storage of information and protection against interferences. It has been proposed that long-term potentiation (LTP), the long-lasting enhancement. of synaptic transmission, is a cellular model for memory consolidation. Since consolidation of several forms of memory is facilitated by paradoxical sleep (PS) we ask whether PS modulates the cellular and molecular pathways underlying LTP. The long-lasting form of LTP (L-LTP) is dependent on the activation of transcription factors, enzymatic cascades and the secreted neurotrophin BDNF. By using PS deprivation, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR), we showed that an increase in PS amount (produced by rebound in PS deprived rats) is able to up-regulate the expression level of transcription factors Zif268 and c-Fos as well as Arc and BDNF in the CA1 and CA3 areas of the hippocampus. Several studies involved these factors in dendritic protein synthesis and in long-term structural changes of synapses underlying L-LTP. The present study together with the work of others (Ribeiro et al., 2002) suggest that by this mechanism, a post-learning increase in PS quantity (post-learning PS window) could convert a transient form of LTP to L-LTP. © 2014 Elsevier Inc.


Caporale A.,University of Rome La Sapienza | Palombo M.,University of Rome La Sapienza | Palombo M.,CEA Fontenay-aux-roses | Macaluso E.,Lyon Neuroscience Research Center | And 3 more authors.
NeuroImage | Year: 2017

Motivated by previous results obtained in vitro, we investigated the dependence of the anomalous diffusion (AD) MRI technique on local magnetic susceptibility differences (Δχ) driven by magnetic field inhomogeneity in human brains. The AD-imaging contrast investigated here is quantified by the stretched-exponential parameter γ, extracted from diffusion weighted (DW) data collected by varying diffusion gradient strengths. We performed T2* and DW experiments in eight healthy subjects at 3.0 T. T2*-weighted images at different TEs=(10,20,35,55) ms and DW-EPI images with fourteen b-values from 0 to 5000 s/mm2 were acquired. AD-metrics and Diffusion Tensor Imaging (DTI) parameters were compared and correlated to R2* and to Δχ values taken from literature for the gray (GM) and the white (WM) matter. Pearson's correlation test and Analysis of Variance with Bonferroni post-hoc test were used. Significant strong linear correlations were found between AD γ-metrics and R2* in both GM and WM of the human brain, but not between DTI-metrics and R2*. Depending on Δχ driven magnetic field inhomogeneity, the new contrast provided by AD-γ imaging reflects Δχ due to differences in myelin orientation and iron content within selected regions in the WM and GM, respectively. This feature of the AD-γ imaging due to the fact that γ is quantified by using MRI, may be an alternative strategy to investigate, at high magnetic fields, microstructural changes in myelin, and alterations due to iron accumulation. Possible clinical applications might be in the field of neurodegenerative diseases. © 2017 Elsevier Inc.


Fagioli S.,IRCCS Santa Lucia Foundation | MacAluso E.,IRCCS Santa Lucia Foundation | MacAluso E.,Lyon Neuroscience Research Center
Journal of Cognitive Neuroscience | Year: 2016

Individuals are able to split attention between separate locations, but divided spatial attention incurs the additional requirement of monitoring multiple streams of information. Here, we investigated divided attention using photos of natural scenes, where the rapid categorization of familiar objects and prior knowledge about the likely positions of objects in the real world might affect the interplay between these spatial and nonspatial factors. Sixteen participants underwent fMRI during an object detection task. They were presented with scenes containing either a person or a car, located on the left or right side of the photo. Participants monitored either one or both object categories, in one or both visual hemifields. First, we investigated the interplay between spatial and nonspatial attention by comparing conditions of divided attention between categories and/or locations. We then assessed the contribution of top-down processes versus stimulus-driven signals by separately testing the effects of divided attention in target and nontarget trials. The results revealed activation of a bilateral frontoparietal network when dividing attention between the two object categories versus attending to a single category but no main effect of dividing attention between spatial locations. Within this network, the left dorsal premotor cortex and the left intraparietal sulcus were found to combine task-and stimulus-related signals. These regions showed maximal activation when participants monitored two categories at spatially separate locations and the scene included a nontarget object. We conclude that the dorsal frontoparietal cortex integrates top-down and bottom-up signals in the presence of distractors during divided attention in real-world scenes. © 2016 Massachusetts Institute of Technology.


Kratzer I.,University of Lyon | Vasiljevic A.,University of Lyon | Vasiljevic A.,Lyon Public Hospitals | Rey C.,University of Lyon | And 5 more authors.
Histochemistry and Cell Biology | Year: 2012

The choroid plexus epithelium controls the movement of solutes between the blood and the cerebrospinal fluid. It has been considered as a functionally more immature interface during brain development than in adult. The anatomical basis of this barrier is the interepithelial choroidal junction whose tightness has been attributed to the presence of claudins. We used quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry to identify different claudins in the choroid plexuses of developing and adult rats. Claudin-1, -2, and -3 were highly and selectively expressed in the choroid plexus as compared to brain or parenchyma microvessels and were localized at epithelial junctions. Claudin-6, -9, -19, and -22 also displayed a previously undescribed choroidal selectivity, while claudin-4, -5, and -16 were enriched in the cerebral microvessels. The choroidal pattern of tight junction protein expression in prenatal brains was already complex and included occludin and zonula occludens proteins. It differed from the adult pattern in that the poreforming claudin-2, claudin-9, and claudin-22 increased during development, while claudin-3 and claudin-6 decreased. Claudin-2 and claudin-11 presented a mirror image of abundance between lateral ventricle and fourth ventricle choroid plexuses. Imunohistochemical analysis of human fetal and postnatal brains for claudin-1, -2, and -3 demonstrated their early presence and localization at the apico-lateral border of the choroid plexus epithelial cells. Overall, choroidal epithelial tight junctions are already complex in developing brain. The observed differences in claudin expression between developing and adult choroid plexuses may indicate developmental differences in selective blood-cerebrospinal fluid transport functions. © Springer-Verlag 2012.


Vasylieva N.,Lyon Neuroscience Research Center | Vasylieva N.,University Claude Bernard Lyon 1 | Vasylieva N.,Lyon Institute of Nanotechnologies | Maucler C.,Lyon Neuroscience Research Center | And 9 more authors.
Analytical Chemistry | Year: 2013

Microelectrode biosensors are a promising technique to probe the brain interstitial fluid and estimate the extracellular concentration of neurotransmitters like glutamate. Their selectivity is largely based on maintaining high substrate specificity for the enzymes immobilized on microelectrodes. However, the effect of enzyme immobilization on substrate specificity is poorly understood. Furthermore, the accuracy of biosensor measurements for brain biological extracts has not been reliably established in comparison with conventional analytical techniques. In this study, microelectrode biosensors were prepared using different enzyme immobilization methods, including glutaraldehyde, a conventional cross-linker, and poly(ethylene glycol) diglycidyl ether (PEGDE), a milder immobilization reagent. Glutaraldehyde, but not PEGDE, significantly decreased the apparent substrate specificity of glutamate and glucose oxidase. For glutaraldehyde prepared biosensors, detection of secondary substrates by glutamate oxidase increased, resulting in a significant overestimate of glutamate levels. This effect was not observed with PEGDE-based biosensors, and when brain microdialysates were analyzed, the levels of glutamate detected by biosensors were consistent with those detected by capillary electrophoresis. In addition, basal concentrations of glutamate detected in vivo were approximately 10-fold lower than the levels detected with glutaraldehyde-based biosensors (e.g., 1.2 μM vs 16 μM, respectively). Overall, enzyme immobilization can significantly impact substrate specificity, and PEGDE is well-suited for the preparation of stable and selective biosensors. This development questions some of the previous biosensor studies aimed at detecting glutamate in the brain and opens new possibilities for specific neurotransmitter detection. © 2013 American Chemical Society.


Clement G.,International Space University | Clement G.,Lyon Neuroscience Research Center | Wood S.J.,Azusa Pacific University
PLoS ONE | Year: 2014

The central nervous system must resolve the ambiguity of inertial motion sensory cues in order to derive an accurate representation of spatial orientation. Adaptive changes during spaceflight in how the brain integrates vestibular cues with other sensory information can lead to impaired movement coordination, vertigo, spatial disorientation, and perceptual illusions after return to Earth. The purpose of this study was to compare tilt and translation motion perception in astronauts before and after returning from spaceflight. We hypothesized that these stimuli would be the most ambiguous in the lowfrequency range (i.e., at about 0.3 Hz) where the linear acceleration can be interpreted either as a translation or as a tilt relative to gravity. Verbal reports were obtained in eleven astronauts tested using a motion-based tilt-translation device and a variable radius centrifuge before and after flying for two weeks on board the Space Shuttle. Consistent with previous studies, roll tilt perception was overestimated shortly after spaceflight and then recovered with 1-2 days. During dynamic linear acceleration (0.15-0.6 Hz, 61.7 m/s2) perception of translation was also overestimated immediately after flight. Recovery to baseline was observed after 2 days for lateral translation and 8 days for fore-aft translation. These results suggest that there was a shift in the frequency dynamic of tilt-translation motion perception after adaptation to weightlessness. These results have implications for manual control during landing of a space vehicle after exposure to microgravity, as it will be the case for human asteroid and Mars missions. Copyright: © 2014 Zhou et al.


Schon D.,Aix - Marseille University | Schon D.,French Institute of Health and Medical Research | Tillmann B.,Lyon Neuroscience Research Center | Tillmann B.,University of Lyon
Annals of the New York Academy of Sciences | Year: 2015

This paper brings together different perspectives on the investigation and understanding of temporal processing and temporal expectations. We aim to bridge different temporal deficit hypotheses in dyslexia, dysphasia, or deafness in a larger framework, taking into account multiple nested temporal scales. We present data testing the hypothesis that temporal attention can be influenced by external rhythmic auditory stimulation (i.e., musical rhythm) and benefits subsequent language processing, including syntax processing and speech production. We also present data testing the hypothesis that phonological awareness can be influenced by several months of musical training and, more particularly, rhythmic training, which in turn improves reading skills. Together, our data support the hypothesis of a causal role of rhythm-based processing for language processing and acquisition. These results open new avenues for music-based remediation of language and hearing impairment. © 2015 New York Academy of Sciences.


Tillmann B.,Lyon Neuroscience Research Center | Tillmann B.,University of Lyon | Albouy P.,Lyon Neuroscience Research Center | Albouy P.,University of Lyon | And 2 more authors.
Handbook of Clinical Neurology | Year: 2015

In contrast to the sophisticated music processing reported in the general population, individuals with congenital amusia show deficits in music perception and production. Congenital amusia occurs without brain damage, sensory or cognitive deficits, and has been suggested as a lifelong deficit with genetic origin. Even though recognized for a long time, this disorder has been systematically studied only relatively recently for its behavioral and neural correlates. The currently most investigated hypothesis about the underlying deficits concerns the pitch dimension, notably with impaired pitch discrimination and memory. Anatomic and functional investigations of pitch processing revealed that the amusic brain presents abnormalities in the auditory and inferior frontal cortices, associated with decreased connectivity between these structures. The deficit also impairs processing of pitch in speech material and processing of the time dimension in music for some of the amusic individuals, but does not seem to affect spatial processing. Some studies suggest at least partial dissociation in the disorder between perception and production. Recent studies revealed spared implicit pitch perception in congenital amusia, supporting the power of implicit cognition in the music domain. Current challenges consist in defining different subtypes of congenital amusia as well as developing rehabilitation programs for this "musical handicap.". © 2015 Elsevier B.V.


El Yacoubi M.,Lyon Neuroscience Research Center | Rappeneau V.,Lyon Neuroscience Research Center | Champion E.,Lyon Neuroscience Research Center | Malleret G.,Lyon Neuroscience Research Center | Vaugeois J.-M.,Lyon Neuroscience Research Center
Behavioural Brain Research | Year: 2013

Cardinal symptoms of depression include helplessness and anhedonia. In addition, depression and anxiety are often comorbid disorders. H/Rouen mice, a genetic mouse model of depression, display helpless behavior in the tail suspension test, whereas non-helpless NH/Rouen mice show the opposite behavior. It is unknown whether H/Rouen mice display an anxious behavior as compared to NH/Rouen mice, and is unclear whether they display anhedonia. Time spent in the periphery of an open-field, an index of anxiety, was found to be higher in male and female H/Rouen mice as compared to NH/Rouen mice. In the elevated plus-maze, a decrease in the number of entries and in the time spent in the open arms was observed in both male and female H/Rouen. In the light/dark box, the number of entries and the time spent in the anxiogenic bright compartment was significantly reduced in male and female H/Rouen mice. In addition, the preference of consumption of a 2% sucrose solution was significantly reduced in male and female H/Rouen mice as compared to NH/Rouen and I/Rouen mice in a two-bottle choice paradigm but was restored by a chronic (3 weeks) fluoxetine treatment. H/Rouen mice thus display both anxiety and anhedonia making them a potent animal model in the treatment of forms depression comorbidly expressed with anxiety. © 2013 .


Strazielle N.,Lyon Neuroscience Research Center | Ghersi-Egea J.F.,French Institute of Health and Medical Research
Molecular Pharmaceutics | Year: 2013

The brain develops and functions within a strictly controlled environment resulting from the coordinated action of different cellular interfaces located between the blood and the extracellular fluids of the brain, which include the interstitial fluid and the cerebrospinal fluid (CSF). As a correlate, the delivery of pharmacologically active molecules and especially macromolecules to the brain is challenged by the barrier properties of these interfaces. Blood-brain interfaces comprise both the blood-brain barrier located at the endothelium of the brain microvessels and the blood-CSF barrier located at the epithelium of the choroid plexuses. Although both barriers develop extensive surface areas of exchange between the blood and the neuropil or the CSF, the molecular fluxes across these interfaces are tightly regulated. Cerebral microvessels acquire a barrier phenotype early during cerebral vasculogenesis under the influence of the Wnt/β-catenin pathway, and of recruited pericytes. Later in development, astrocytes also play a role in blood-brain barrier maintenance. The tight choroid plexus epithelium develops very early during embryogenesis. It is specified by various signaling molecules from the embryonic dorsal midline, such as bone morphogenic proteins, and grows under the influence of Sonic hedgehog protein. Tight junctions at each barrier comprise a distinctive set of claudins from the pore-forming and tightening categories that determine their respective paracellular barrier characteristics. Vesicular traffic is limited in the cerebral endothelium and abundant in the choroidal epithelium, yet without evidence of active fluid phase transcytosis. Inorganic ion transport is highly regulated across the barriers. Small organic compounds such as nutrients, micronutrients and hormones are transported into the brain by specific solute carriers. Other bioactive metabolites, lipophilic toxic xenobiotics or pharmacological agents are restrained from accumulating in the brain by several ATP-binding cassette efflux transporters, multispecific solute carriers, and detoxifying enzymes. These various molecular effectors differently distribute between the two barriers. Receptor-mediated endocytotic and transcytotic mechanisms are active in the barriers. They enable brain penetration of selected polypeptides and proteins, or inversely macromolecule efflux as it is the case for immnoglobulins G. An additional mechanism specific to the BCSFB mediates the transport of selected plasma proteins from blood into CSF in the developing brain. All these mechanisms could be explored and manipulated to improve macromolecule delivery to the brain. © 2013 American Chemical Society.

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