Summary
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.
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Web resources: | https://cordis.europa.eu/project/id/867458 |
Start date: | 01-09-2019 |
End date: | 31-08-2021 |
Total budget - Public funding: | 147 815,04 Euro - 147 815,00 Euro |
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Original description
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.Status
CLOSEDCall topic
WF-01-2018Update Date
17-05-2024
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