Brain network modules of meaningful and meaningless objects

Network modularity is a key feature for efficient information processing in the human brain. This information processing is however dynamic and networks can reconfigure at very short time period, few hundreds of millisecond. This requires neuroimaging techniques with sufficient time resolution. Here we use the dense electroencephalography, EEG, source connectivity methods to identify cortical networks with excellent time resolution, in the order of millisecond. We identify functional networks during picture naming task. Two categories of visual stimuli were presented, meaningful (tools, animals) and meaningless (scrambled) objects. In this paper, we report the reconfiguration of brain network modularity for meaningful and meaningless objects. Results showed mainly that networks of meaningful objects were more modular than those of meaningless objects. Networks of the ventral visual pathway were activated in both cases. However a strong occipitotemporal functional connectivity appeared for meaningful object but not for meaningless object. We believe that this approach will give new insights into the dynamic behavior of the brain networks during fast information processing.Comment: The 3rd Middle East Conference on Biomedical Engineering (MECBME'16

PP270—Computational modeling of dravet syndrome

e102 Volume 35 Number 8S clorazepate (20mg 2× /d), and pregabalin (100 mg 3× /d). Because of resurgence of severe anxio-depressive symptoms, without any change of the treatment, the patient was readmitted 2 months later. Despite increasing the dose of clomipramine up to 225 mg/d, there was no clinical improvement, and the patient finally attempted to her life by abusing drugs. She then improved after 2 weeks on clomipramine IV (50 mg/d). Compliance was estimated good and no pharmacokinetic interactions with the rest of the treatment were found. C and DC plasma levels were measured, and CYP2D6/CYP2C19 genotype analyzed. Results: The plasma levels of C and DC are given in the Table below. Measures were done at the steady state and at trough concentration for IV treatment and 10 hours after the last dose for oral treatment

Is the functional interaction between adenosine A2A receptors and metabotropic glutamate 5 receptors a general mechanism in the brain? Differences and similarities between the striatum and the hippocampus

The aim of the present paper was to examine, in a comparative way, the occurrence and the mechanisms of the interactions between adenosine A2A receptors (A2ARs) and metabotropic glutamate 5 receptors (mGlu5Rs) in the hippocampus and the striatum. In rat hippocampal and corticostriatal slices, combined ineffective doses of the mGlu5R agonist 2-chloro-5-hydroxyphenylglycine (CHPG) and the A2AR agonist CGS 21680 synergistically reduced the slope of excitatory postsynaptic field potentials (fEPSPs) recorded in CA1 and the amplitude of field potentials (FPs) recorded in the dorsomedial striatum. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway appeared to be involved in the effects of CGS 21680 in corticostriatal but not in hippocampal slices. In both areas, a postsynaptic locus of interaction appeared more likely. N-methyl-D-aspartate (NMDA) reduced the fEPSP slope and FP amplitude in hippocampal and corticostriatal slices, respectively. Such an effect was significantly potentiated by CHPG in both areas. Interestingly, the A2AR antagonist ZM 241385 significantly reduced the NMDA-potentiating effect of CHPG. In primary cultures of rat hippocampal and striatal neurons (ED 17, DIV 14), CHPG significantly potentiated NMDA-induced lactate dehydrogenase (LDH) release. Again, such an effect was prevented by ZM 241385. Our results show that A2A and mGlu5 receptors functionally interact both in the hippocampus and in the striatum, even though different mechanisms seem to be involved in the two areas. The ability of A2ARs to control mGlu5R-dependent effects may thus be a general feature of A2ARs in different brain regions (irrespective of their density) and may represent an additional target for the development of therapeutic strategies against neurological disorders

Neuron to Astrocyte Communication via Cannabinoid Receptors Is Necessary for Sustained Epileptiform Activity in Rat Hippocampus

Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus

Deleterious GRM1 Mutations in Schizophrenia

We analysed a phenotypically well-characterised sample of 450 schziophrenia patients and 605 controls for rare non-synonymous single nucleotide polymorphisms (nsSNPs) in the GRM1 gene, their functional effects and family segregation. GRM1 encodes the metabotropic glutamate receptor 1 (mGluR1), whose documented role as a modulator of neuronal signalling and synaptic plasticity makes it a plausible schizophrenia candidate. In a recent study, this gene was shown to harbour a cluster of deleterious nsSNPs within a functionally important domain of the receptor, in patients with schizophrenia and bipolar disorder. Our Sanger sequencing of the GRM1 coding regions detected equal numbers of nsSNPs in cases and controls, however the two groups differed in terms of the potential effects of the variants on receptor function: 6/6 case-specific and only 1/6 control-specific nsSNPs were predicted to be deleterious. Our in-vitro experimental follow-up of the case-specific mutants showed that 4/6 led to significantly reduced inositol phosphate production, indicating impaired function of the major mGluR1signalling pathway; 1/6 had reduced cell membrane expression; inconclusive results were obtained in 1/6. Family segregation analysis indicated that these deleterious nsSNPs were inherited. Interestingly, four of the families were affected by multiple neuropsychiatric conditions, not limited to schizophrenia, and the mutations were detected in relatives with schizophrenia, depression and anxiety, drug and alcohol dependence, and epilepsy. Our findings suggest a possible mGluR1 contribution to diverse psychiatric conditions, supporting the modulatory role of the receptor in such conditions as proposed previously on the basis of in vitro experiments and animal studies

Two distinct signaling pathways upregulate NMDA receptor responses via two distinct metabotropic glutamate receptor subtypes

Molecular processes regulating the gain of NMDA receptors modulate diverse physiological and pathological responses in the CNS. Group I metabotropic glutamate receptors (mGluRs), which neighbor NMDA receptors and which can be coactivated by synaptically released glutamate, couple to several different second messenger pathways, each of which could target NMDA receptors. In CA3 pyramidal cells we show that the activation of mGluR1 potentiates NMDA current via a G-protein-independent mechanism involving Src kinase activation. In contrast, mGluR5-mediated enhancement of NMDA current requires G-protein activation, triggering a signaling cascade including protein kinase C and Src. These results indicate that one neurotransmitter, glutamate, can activate two distinct and independent signaling systems to target the same effector. These two pathways are likely to contribute significantly to the highly differentiated control of NMDA receptor function

Metabotropic glutamate receptors: intracellular signaling pathways.

Metabotropic glutamate receptors are classified into three groups, primarily on the basis of sequence similarity and whether they positively couple to the phospholipase C cascade or negatively couple to adenylyl cyclases. The past decade of research, drawing on sophisticated molecular approaches, has revealed a multitude of additional intracellular components that assemble as protein scaffolds around neuronal metabotropic glutamate receptors, establishing functional links to postsynaptic density structures, to membrane-bound enzymes and ion channels, and to the nucleus. Characterization of these novel transduction mechanisms is providing new insights into the roles of metabotropic glutamate receptors in the regulation and modulation of diverse functions in the nervous system

Détection d'objets complexes par fusion d'informations : Application à la détection d'aéroports dans les images satellitales

Cet article aborde quelques problèmes pratiques rencontrés clans le cadre de la détection automatique d'aéroports dans des images satellitales. Nous évoquerons en particulier les difficultés liées à l'utilisation d'informations issues de capteurs différents : problème de géo-référencement imprécis, et de fusion d'algorithmes

Muscarinic receptor stimulation reduces NMDA responses in CA3 hippocampal pyramidal cells via Ca2+-dependent activation of tyrosine phosphatase.

N-methyl-D-aspartate (NMDA)-type glutamate receptors perform critical functions during the development of the nervous system and in the initiation of synaptic plasticity. An important mechanism in setting the gain of NMDA receptors involves the stimulation of G-protein-coupled receptors (GPCRs), which through activation of protein tyrosine kinases leads to an upregulation of NMDA receptors. In contrast, little is known about how NMDA receptors are downregulated. In the present study, we characterized a signaling pathway that mediates the depression of NMDA receptor function in response to stimulation of muscarinic acetylcholine receptors. Whole-cell patch-clamp recordings obtained from CA3 pyramidal cells in organotypic slice cultures revealed that under conditions of low intracellular calcium buffering application of muscarine-depressed NMDA receptor current. The sensitivity of this response to pirenzipine indicated that the M1 acetylcholine receptor is mediating this depression. The muscarine-induced depression of NMDA current was prevented by blocking G-protein function or after depleting intracellular Ca2+ stores with cyclopiazonic acid. Inhibitors of calmodulin prevented the depression whereas blocking calcineurin enhanced the depression of NMDA currents. Blocking tyrosine phosphatase activity with pervanandate converted the muscarine-induced depression into a potentiation of NMDA currents, whereas blocking protein kinase A (H-89), Src kinase (PP2, SU6656), or PKC (GF 109203X) failed to prevent the depression of NMDA currents. As Src tyrosine kinase is known to phosphorylate and upregulate NMDA receptors, we propose that a protein tyrosine phosphatase(s) counteracting the action of Src is the final target in the mAChR-dependent inhibitory signaling cascade. Our data are consistent with a transduction cascade comprising an M1 acetylcholine receptor-->G-protein-->Ca2+ release-->calmodulin-->tyrosine phosphatase

Properties and development of calcium currents in embryonic cockroach neurons.

International audienceIn freshly dissociated neurons from embryonic cockroach (Periplaneta americana L.) brains, voltage-dependent calcium currents appear early in development (E14). Their intensity increases progressively during embryonic life until eclosion (E35). Their time course and voltage dependency are characteristic of high voltage activated (HVA) currents although a 10 mV shift of the I/V curve towards more negative potentials was observed between E18 and E23. Their sensitivity to omega-AgaTx-IVA and omega-CgTx-GVIA and insensitivity to both amiloride and isradipine indicate that the corresponding channels are of the P/Q and N types. These channels, as well as a small proportion of toxin-resistant (R) channels (about 20%), are blocked by mibefradil and verapamil. The physiological significance of these currents and their modifications during embryonic life is discussed