The molecular pathways and neuronal circuits that underpin the effect of neuropeptide galanin on sleep homeostasis.

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Sleep pressure increases as a function of wakefulness. Prolonged sleep deprivation causes homeostatic rebound sleep. Homeostasis is fundamental component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Yet, little is known about the molecular pathways and circuitry which underpins homeostatic sleep regulation. Previously, the Rihel laboratory has demonstrated a role for the neuropeptide galanin in homeostatic sleep regulation in zebrafish larvae. Galanin-expressing neurons were shown to be active during rebound sleep, induction of galanin transcripts was predictive of total rebound sleep, and galanin mutants lack rebound sleep following elevated neural activity and sleep deprivation. This project will continue this work using zebrafish (Danio Rerio) as a model organism. Zebrafish are small, fast-developing and diurnal. They show behavioral, physiological, and pharmacological characteristics of mammalian sleep. Optical transparency at the larval stage make visualisation of neuron activity, at single cell resolution, possible using intracellular fluorescent markers of calcium responses. Zebrafish are an established model system for the genetic dissection of sleep, facilitated by advanced, well-annotated genetic maps. This model also has the additional benefit of allowing large scale genetic screens.Within this model, the project will investigate the molecular pathways and neuronal circuits which underpin the observed effect of neuropeptide galanin on sleep homeostasis. Initially the focus of the project will be on the downstream signaling pathway and neuron circuitry. The circuitry downstream of galanin-expressing neurons will be investigated using imaging techniques. Molecular techniques, including genetic knock down, will be used to establish the receptor downstream of galanin signaling. There is scope within this project to investigate the upstream effectors of galanin-mediated sleep homeostasis. Preliminary data from the Rihel laboratory suggests a role for glia upstream of galanin-expressing neurons which requires further investigation.