Mapping the Genes and Neurons that Regulate Sleep Homeostasis (360G-Wellcome-217150_Z_19_Z)

£1,647,968

Although sleep is highly conserved and has a major impact on human health, the genetic and neuronal mechanisms that regulate the timing and amount of sleep remain poorly resolved. From a combination of whole-brain activity mapping, targeted gene editing, and behavioural analysis, we have discovered that neurons in the zebrafish preoptic area that express the neuropeptide Galanin become activated during rebound sleep and that proper sleep homeostasis requires functional Galanin. We will now use RNA sequencing, pharmacology, and mutant analysis to dissect the signals that converge onto Galanin-mediated sleep homeostasis. Second, we will leverage the optical translucency of the zebrafish brain and genetically encoded calcium indicators to image Galanin neurons’ activity in relation to known wake-promoting circuits, such as Hypocretin and Noradrenaline neurons, in vivo. Finally, we will use chemogenetic tools to manipulate the activity of Galanin neurons during and after normal and homeostatic rebound sleep to elucidate the functional role these neurons play in sleep regulation.

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Grant Details

Amount Awarded 1647968
Applicant Surname Rihel
Approval Committee Science Interview Panel
Award Date 2019-07-16T00:00:00+00:00
Financial Year 2018/19
Grant Programme: Title Investigator Award in Science
Internal ID 217150/Z/19/Z
Lead Applicant Dr Jason Rihel
Partnership Value 1647968
Planned Dates: End Date 2024-10-01T00:00:00+00:00
Planned Dates: Start Date 2019-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London