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Investigating the coupling between synaptic activity and cerebral blood flow in the olfactory glomerulus in vivo using two-photon laser scanning microscopy

Objective

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, and
3) 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.

Call for proposal

FP6-2004-MOBILITY-6
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Coordinator

CHARITé - UNIVERSITäTSMEDIZIN BERLIN
Address
Schumannstr. 20-21
Berlin
Germany

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Participants (1)

PRESIDENT AND FELLOWS OF HARVARD COLLEGEDEPARTMENT OF MOLECULAR AND CELLULAR BIOLOGY
United States
Address
Office Of Sponsored Programs, 1350 Massachusetts Avenue, 6th Floor
Cambridge, Ma

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