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Deciphering the effects of locus coeruleus activity on whole-brain dynamics and neurovascular coupling

Project description

How blue spots in brainstem modulate whole-brain dynamics

The locus coeruleus (LC) is a set of blue spots found in the brainstem, where the base of the brain connects to the spinal cord. Its neural cells are blue because they make and release a specific chemical signal called noradrenaline – a stress signal released when we experience fear and stress. The EU-funded LC-FMRI project will assess whole-brain responses and functional network reconfiguration. Using ultra-high field functional magnetic resonance imaging (fMRI), it will perform an optogenetic LC stimulation in awake mice to avoid the effects of anaesthesia. The project will lay the foundation for studying how LC modulates whole-brain dynamics in health and disease using fMRI, with high potential for translation to biomedical applications.

Objective

Locus coeruleus (LC) regulates vital autonomous and cognitive functions and has recently gained interest as a clinical target in neurodegenerative and psychiatric disorders. Previous studies have investigated the effect of LC activity on small groups of neurons and on endpoint behavior. However, LC’s widespread connections and broad downstream effects make a systems-level approach imperative for comprehensively understanding LC function. In LC-FMRI, we will perform highly specific optogenetic LC stimulation in mice and assess whole-brain responses and functional network reconfiguration using ultra-high field functional magnetic resonance imaging (fMRI). To decipher neural, astrocytic and vascular contributions to LC-induced fMRI responses, we will acquire simultaneous optical calcium recordings during fMRI. Experiments will be performed in awake mice to circumvent confounding effects of anesthesia on LC function. Finally, we will investigate how LC stimulation affects whole-brain dynamics and neurovascular coupling in the context of sensory processing. Our project will lay the foundation for studying how LC modulates whole-brain dynamics in health and disease using fMRI, with high potential for translation to human applications.

Call for proposal

H2020-WF-2018-2020

See other projects for this call

Sub call

H2020-WF-01-2018

Coordinator

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Net EU contribution
€ 147 815,04
Address
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 Lisboa
Portugal

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Region
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Research Organisations
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Total cost
€ 147 815,04