Objectif Neuronal activation induces a spatially and temporally confined increase in cerebral blood flow. This neuro-vascular coupling forms the physiological basis of functional magnetic resonance imaging. Neuro-vascular coupling has been implicated as a major patho physiological factor in stroke, brain trauma, migraine, Alzheimer's disease, and aging. However, the cellular and sub-cellular mechanisms that govern neuro-vascular coupling are largely unknown. It has been hypothesised that astrocytes may convert neuronal activity into changes in vessel diameter. Indeed, glutamate released by stimulated neurons increases astrocytic calcium levels in brain slices.However, the astrocytic calcium surge may induce both vasodilation and vasoconstriction, depending on the triggering techniques and pharmacological pre-treatment. Investigating these open issues in vivo has been hampered by the low spatial resolution of most blood flow measurement techniques. Recently, two-photon laser scanning microscopy (2PLSM) has been shown to accurately and non-invasively measure capillary blood flow in vivo with high resolution. The aim of this project is to use 2PLSM to image synaptic activity in vivo in olfactory glomeruli of transgenic mice expressing pH-sensitive fluorescent proteins that are genetically targeted to the synapse, and to simultaneously measure astrocytic calcium levels and capillary blood flow using fluorescent markers.Specifically, the goal is to:1) determine the temporal and spatial pattern by which synaptic activity leads to vascular changes,2) identify the changes in vascular diameter triggered by physiological astrocytic calcium elevations and the molecular pathways that underlie them, and3) investigate how and to what extend neuro-vascular coupling becomes perturbed in aged mice and in an animal model of cerebral ischaemia.The project may help to understand the physiological basis of neuro-imaging techniques and the role of neuro-vascular coupling in neurological diseases. Champ scientifique medical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicineneurologystrokemedical and health sciencesclinical medicineclinical neurology Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Thème(s) MOBILITY-2.2 - Marie Curie Outgoing International Fellowships (OIF) Appel à propositions FP6-2004-MOBILITY-6 Voir d’autres projets de cet appel Régime de financement OIF - Marie Curie actions-Outgoing International Fellowships Coordinateur CHARITé - UNIVERSITäTSMEDIZIN BERLIN Contribution de l’UE Aucune donnée Adresse Schumannstr. 20-21 BERLIN Allemagne Voir sur la carte Liens 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 PRESIDENT AND FELLOWS OF HARVARD COLLEGEDEPARTMENT OF MOLECULAR AND CELLULAR BIOLOGY États-Unis Contribution de l’UE Aucune donnée Adresse Office of Sponsored Programs, 1350 Massachusetts Avenue, 6th Floor CAMBRIDGE, MA Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée