Resolving the Neuropharmacology and Genetics of Zebrafish Sleep

Objective

Sleep is a fundamental process, yet the genetic and neural mechanisms that regulate sleep are largely unknown. We have developed the zebrafish as a model system to study the regulation of sleep because it combines the genetics of invertebrates with the basic brain structures that regulate sleep in humans. We previously designed high throughput behavioural assays to measure sleep behaviours in the fish and used genetic tools to demonstrate that the wake-regulating hypocretin/orexin (Hcrt) system is functionally conserved in the zebrafish. We have also used our assays to perform a small molecule screen and identified both conserved and novel candidate regulators of sleep in zebrafish.

In Aim 1, we will observe the behaviour of wild type and Hcrt receptor mutants to a panel of small molecules known to alter zebrafish sleep. This aim tests the hypothesis that these compounds exert their effects on sleep and wake through the Hcrt system. In Aim 2, we will follow-up on the compounds that had differential effects in the mutants. We will monitor the activity of Hcrt neurons in response to drugs using a new neuroluminescent technique to observe the activity of neurons in freely behaving zebrafish larvae. This Aim will extend the behavioural data to the level of neural circuits. In Aim 3, we will use new methods to globally observe neuronal activity in the zebrafish brain to extend our analysis to neurons thought to interact with the Hcrt system. By observing activity across the sleep/wake cycle, we may also uncover novel sleep regulating neurons.

Overall, this project takes a multidisciplinary approach to the study of sleep and the Hcrt system, leveraging new methods from chemical biology, molecular genetics, and behavioural neuroscience in the zebrafish. As little is known about the mechanisms and sites of action for most sleep-altering compounds, any progress would advance the sleep field and could have clinical relevance to the treatment of sleep disorders.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• medical and health sciences clinical medicine psychiatry sleep disorders
• natural sciences biological sciences neurobiology
• natural sciences biological sciences genetics
• natural sciences biological sciences molecular biology molecular genetics
• natural sciences biological sciences zoology invertebrate zoology

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• ERC-SG-LS5 - ERC Starting Grant - Neurosciences and neural disorders

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2011-StG_20101109
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-SG - ERC Starting Grant

Host institution

Beneficiaries (1)