SEROTONINSLEEP

SEROTONERGIC REGULATION OF SLEEP RELATED NEURAL CIRCUIT

 Coordinatore UNIVERSITY COLLEGE LONDON 

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Ms.
Nome: Malgorzata
Cognome: Kielbasa
Email: send email
Telefono: 4420310000000
Fax: 442078000000

 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

# participant  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON

 Organization address address: GOWER STREET
city: LONDON
postcode: WC1E 6BT

contact info
Titolo: Ms.
Nome: Malgorzata
Cognome: Kielbasa
Email: send email
Telefono: 4420310000000
Fax: 442078000000

UK (LONDON) coordinator 231˙283.20

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regulation    human    ht    behaving    fish    direct    sleep    hcrt    optogenetic    neural    zebrafish    circuits    behavior    neurons    mechanisms    brain   

 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.'

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