Objective Traumatic events such as strokes or lesions to the adult brain can trigger large-scale reorganization of neuronal activity thought to be critical for functional recovery. The anatomical and molecular events underlying such reorganization remain an enigma. While rapid and short term changes of connections at the synaptic scale are widely studied, little is known about the principles and mechanisms of long-term and large-scale reorganization of axonal branches in mature circuits. I hypothesize that long-range axonal branching events in a minority of neurons contribute significantly to the plasticity and reorganization of adult neuronal circuits via unknown intrinsic mechanisms of axons survival and extrinsic environmental cues. A major reason why so little is known about axon dynamics in the adult brain has been the immense technical challenge of imaging rare axonal events in the dense meshwork of the adult brain. To solve this problem, I will apply new 3D imaging and genetic tools I developed to help visualize and quantify axons and synapses in the whole brain in an unbiased way. First, I will study the brain-wide neurite and synaptic dynamics after lesion and their effect on circuit function and homeostasis to shed light on the scale of brain plasticity. Second, I will characterize the intrinsic molecular pathways controlling activity-driven branch dynamics with viral approaches. I will make extensive use of tissue clearing, 3D imaging, and state-of-the-art image analysis pipelines to streamline the analysis of neuronal network properties. Third, I will investigate the extrinsic molecular and environmental factors promoting axonal dynamics in the context of adult brain structural plasticity. By generating a conceptual and mechanistic framework for the properties and mechanisms of injury induced brain reorganization, this study may contribute to the future design of new strategies to promote brain repair and curb the progress of neurodegenerative diseases. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologystrokemedical and health sciencesbasic medicinephysiologyhomeostasis Keywords NeuroRemod Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-STG - ERC Starting Grant Call for proposal ERC-2017-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Net EU contribution € 1 253 046,21 Address RUE DE TOLBIAC 101 75654 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 493 750,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Net EU contribution € 1 253 046,21 Address RUE DE TOLBIAC 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 493 750,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE France Net EU contribution € 240 703,79 Address BOULEVARD DE L'HOPITAL 47 75013 Paris See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 240 703,79
