SEROTONINSLEEP
SEROTONERGIC REGULATION OF SLEEP RELATED NEURAL CIRCUIT
| Coordinatore | UNIVERSITY COLLEGE LONDON
Organization address
address: GOWER STREET contact info |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 231˙283 € |
| EC contributo | 231˙283 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2012-IIF |
| Funding Scheme | MC-IIF |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-09-01 - 2015-08-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
UNIVERSITY COLLEGE LONDON
Organization address
address: GOWER STREET contact info |
UK (LONDON) | coordinator | 231˙283.20 |
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Obiettivo del progetto (Objective)
'Summary: The appropriate regulation of sleep and wakefulness is a fundamental biological process that impacts human health, cognitive performance, and quality of life. However, the neural mechanisms regulating sleep/wake behavior and its associated circuits in the brain are largely unknown. Recent studies have illustrated the role of hypocretin/orexin (Hcrt) in sleep regulation, but the mechanisms that control the Hcrt system and subsequent changes in neural circuit function are still poorly described. I will take advantage of the larval zebrafish, a genetically and optically accessible model organism whose brain shares basic sleep-related structures with the human brain, in order to systematically investigate how and to what extent serotonergic (5-hydroxytrypamine, 5-HT) neurons of the dorsal raphe nucleus exert effects on sleep cycles via the Hcrt system and associated downstream circuitry. Furthermore, I will disambiguate whether 5-HT neurons affect sleep by direct influence on Hcrt neuron activity or by signalling downsteam on Hcrt target neurons. These analyses require a multidisciplinary approach possible only in zebrafish. First, I will use a novel bioluminescence-based method to investigate how drugs that target the 5-HT system, alter the activity of Hcrt and 5-HT neurons in freely behaving fish. Second, in order to verify a causal relationship between activity in 5-HT and Hcrt neurons and observed behavioral changes, I will activate the same neural populations with optogenetic methods while monitoring behavior in freely behaving fish. Third, I will use the same pharmacological and optogenetic approaches to visualize the direct effects of specific subpopulations of 5-HT and Hcrt neurons on activity throughout the whole brain with functional two-photon calcium imaging. The results of these experiments will provide invaluable insights into how specific neuromodulatory systems interact with each other in order to regulate neural circuits underlying sleep.'