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Home Projects 1st call (2008) 7. High-resolution optical imaging of neurometabolic and neurovascular coupling mechanims in the rodent cortex

7. High-resolution optical imaging of neurometabolic and neurovascular coupling mechanims in the rodent cortex

Dr. P. Magistretti (EPFL), Dr. M. Rudin (ETHZ) - PhD student: Elena Migacheva

Project finished in December 2012.

The advent of functional neuroimaging methods - above all of magnetic resonance imaging (fMRI) - has revolutionized the neuroscience. Spatial maps of brain activation can be obtained in the human brain during different tasks, ranging from perception to motor action and to reasoning and planning. As suggested more than a century ago (Rory and Sherrington, 1890) the underlying principle of the most frequently used methods (e.g. blood oxygen level dependent fMRI (Ogawa et al., 1990) is the brain's active and local regulation of blood flow. Because the brain essentially lacks storage capacietites for energy substrates, monitoring the local cerebral blood suppply and energy metabolism allows the tracking of neuronal activity changes. The non-invasiveness of fMRI and the widespread availability of MR scanners have lead to a vast number of studies applying fMRI, although many of the signal's underlying mechanisms are only poorly understood. The key question is how the involved cellular ensemble (neurons, astrocytes, endothelian cells) is orchestrated in order to meet the energetic demands related to neuronal activity. Indeed there is increasing evidence that astrocytes play a key role in coupling synaptic activity to both blood flow and energy metabolism. For this, we propose an ambitious project involving the development and application of in-vivo quantitative imaging of neurometabolic and neurovascular coupling mechanisms using optical methods in the rodent cortex.

Specfic aims

A. Development of a fully quantitative high resolution optical imaging scheme for measuring cerebral metabolic rate for oxygen (CMRO2) and cerebral flood flow (CBF). This development is based on a novel multimodal optical imaging approach and on modeling.

B. Investigate trial by trial relationship between CMRO2, CBF and neuronal activity in response to sensory stimulation.

C. Study effects of local administration of pharmacological agents interferring with glutamaterrgic transmission (e.g. glutamate receptor agonists/antagonists, glutamate transporter inhibitors) on i) basal CMRO2, CBF and neuronal activity and ii) response to activation with the aim to investigate the dynamics of cerebral metabolism.

Contact: Elena Migacheva