Objetivo The mammalian nervous system is in some respect surprisingly robust to perturbations, as suggested by the virtually complete recovery of brain function after strokes or the pre-clinical asymptomatic phase of Parkinson’s disease. Ultimately though, cognitive and behavioral robustness relies on the ability of single neurons to cope with perturbations, and in particular to maintain a constant and reliable transfer of information.So far, the main facet of robustness that has been studied at the neuronal level is homeostatic plasticity of electrical activity, which refers to the ability of neurons to stabilize their activity level in response to external perturbations. But neurons are also able to maintain their function when one of the major ion channels underlying their activity is deleted or mutated: the number of ion channel subtypes expressed by most excitable cells by far exceeds the minimal number of components necessary to achieve function, offering great potential for compensation when one of the channel’s function is altered. How ion channels are dynamically co-regulated to maintain the appropriate pattern of activity has yet to be determined.In the current project, we will develop a systems-level approach to robustness of neuronal activity based on the combination of electrophysiology, microfluidic single-cell qPCR and computational modeling. We propose to i) characterize the electrical phenotype of dopaminergic neurons following different types of perturbations (ion channel KO, chronic pharmacological treatment), ii) measure the quantitatives changes in ion channel transcriptome (40 voltage-dependent ion channels) associated with these perturbations and iii) determine the mathematical relationships between quantitative changes in ion channel expression and electrical phenotype. Although focused on dopaminergic neurons, this project will provide a general framework that could be applied to any type of excitable cell to decipher its code of robustness. Ámbito científico natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologystrokemedical and health sciencesbasic medicineneurologyparkinson Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-CG-2013-LS5 - ERC Consolidator Grant - Neurosciences and Neural Disorders Convocatoria de propuestas ERC-2013-CoG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-CG - ERC Consolidator Grants Institución de acogida INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Aportación de la UE € 1 972 796,60 Dirección RUE DE TOLBIAC 101 75654 Paris Francia Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Investigador principal Jean-Marc Goaillard (Dr.) Contacto administrativo Dominique Nobile (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Francia Aportación de la UE € 1 972 796,60 Dirección RUE DE TOLBIAC 101 75654 Paris Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Investigador principal Jean-Marc Goaillard (Dr.) Contacto administrativo Dominique Nobile (Mr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos