Objectif Given the persistence of stress-related disorders, it is critical to identify the circuits, cells and mechanisms that fail to recover from stressor exposure. The stress hormone glucocorticoid causes reversible remodeling of brain circuits involved in cognitive, executive and hedonic behaviors. While small amounts of glucocorticoids support cognition and spine synapse turnover, excess stimulation by glucocorticoids predisposes to stress disorders via the loss of dendritic spines. To date, however, because of the paucity of knowledge of underlying mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. My model predicts a fine balance exists between the spine formation and spine elimination needed for behavioral adaptation to stress. Which spines survive, which spines are eliminated may encode the structural basis of learning adaptive behavior. There is hope that promoting dendritic spine turnover facilitates recovery from stressful experience, and paves the road for the discovery of better drug treatments for disorders featuring disrupted glucocorticoid circadian rhythms. One hypothesis to account for the onset and severity of these disorders is that glucocorticoid actions diverge as a function of brain-derived neurotrophic factor (BDNF) signaling. Using mouse genetics, behavior, in vivo imaging and transcriptomic, the “SPICED” project aims at charactering a novel neurotrophic-sensing mechanism of glucocorticoid actions on spine turnover in changing environment. The SPICED project capitalizes on robust preliminary data arguing that BDNF signaling employs the phosphorylated glucocorticoid receptor (GR) as transcription factor to produce a unique gene expression signature. Should BDNF-induced GR phosphorylation become impaired, appropriate turnover of dendritic spines to durable stress or excess glucocorticoids may be inhibited thus setting the stage for neural network wiring defects and development of neuropsychiatric disorders. Champ scientifique natural sciencesbiological sciencesgeneticsnatural sciencescomputer and information sciencesartificial intelligencecomputational intelligence Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Contribution de l’UE Aucune donnée Adresse RUE MICHEL ANGE 3 75794 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Guillaume Rochet (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Participants (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Participation terminée France Contribution de l’UE € 100 000,00 Adresse RUE DE TOLBIAC 101 75654 Paris Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif William Lepetit (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
