Processus cognitifs et différenciation sociale de groupes de rats : intérêt de la modélisation multi-agent.

La situation de difficulté d'accès à la nourriture est un modèle expérimental qui consiste à contraindre des rats à nager jusqu'à une mangeoire et à rapporter la nourriture obtenue dans la cage pour la consommer. L'apparition de la contrainte aquatique va provoquer, au sein d'un groupe de 6 rats, l'émergence d'une différenciation sociale entre des rats Transporteurs qui plongent et ramènent ainsi la nourriture, et des Non-Transporteurs qui ne plongent jamais et se nourrissent en la volant aux premiers. Ce phénomène est stable, reproductible et correspond à un processus auto-organisé impliquant des opérations cognitives d'ordre social. De manière à confirmer cette hypothèse, une modélisation multi-agent (Hamelin) simulant cette situation expérimentale et faisant interagir plusieurs entités non cognitives a été réalisée. Hamelin simule efficacement la différenciation sociale mais fait apparaître des inversions spontanées des statuts sociaux, phénomène qui n'est jamais observé in vivo. Cette discordance entre la réalité biologique et la modélisation multi-agent suggère un rôle pour des processus socio-cognitifs qui contribueraient in vivo à la stabilité des statuts sociaux (version étendue de l'article JCSC

The Psychiatric Risk Gene NT5C2 Regulates Adenosine Monophosphate-Activated Protein Kinase Signaling and Protein Translation in Human Neural Progenitor Cells

Background The 5′-nucleotidase, cytosolic II gene (NT5C2, cN-II) is associated with disorders characterized by psychiatric and psychomotor disturbances. Common psychiatric risk alleles at the NT5C2 locus reduce expression of this gene in the fetal and adult brain, but downstream biological risk mechanisms remain elusive. Methods Distribution of the NT5C2 protein in the human dorsolateral prefrontal cortex and cortical human neural progenitor cells (hNPCs) was determined using immunostaining, publicly available expression data, and reverse transcriptase quantitative polymerase chain reaction. Phosphorylation quantification of adenosine monophosphate-activated protein kinase (AMPK) alpha (Thr172) and ribosomal protein S6 (Ser235/Ser236) was performed using Western blotting to infer the degree of activation of AMPK signaling and the rate of protein translation. Knockdowns were induced in hNPCs and Drosophila melanogaster using RNA interference. Transcriptomic profiling of hNPCs was performed using microarrays, and motility behavior was assessed in flies using the climbing assay. Results Expression of NT5C2 was higher during neurodevelopment and was neuronally enriched in the adult human cortex. Knockdown in hNPCs affected AMPK signaling, a major nutrient-sensing mechanism involved in energy homeostasis, and protein translation. Transcriptional changes implicated in protein translation were observed in knockdown hNPCs, and expression changes to genes related to AMPK signaling and protein translation were confirmed using reverse transcriptase quantitative polymerase chain reaction. The knockdown in Drosophila was associated with drastic climbing impairment. Conclusions We provide an extensive neurobiological characterization of the psychiatric risk gene NT5C2, describing its previously unknown role in the regulation of AMPK signaling and protein translation in neural stem cells and its association with Drosophila melanogaster motility behavior