Visualizing the cellular role of hypothalamic neuronal networks during sleep and wake

All animals tested to date sleep, including simple non-mammalian vertebrates and invertebrates. The sleep/wake cycle is associated with brain-wide changes in cellular processes, such as chromatin modifications, gene expression, protein translation, and synaptic plasticity. We recently showed that sleep is beneficial for nuclear maintenance in neurons. Hypothalamic neuropeptide-secreting neurons, such as the hypocretin/orexin (Hcrt), melanin-concentrating hormone (Mch), and Neurotensin (Nts), are key regulators of sleep and wakefulness. In this work, we dissect the anatomy and study the functional interactions of these hypothalamic neuronal networks in regulating sleep and wakefulness using the zebrafish model. Zebrafish provide the optical and genetic platform that enable us to image in real-time neuronal activity, dynamics of nuclear particles and synaptic plasticity in multiple neuronal circuits during sleep and wake. We found that Nts neurons project toward hypocretin/orexin (Hcrt) and Mch neurons, which express Nts receptor (Ntsr). Furthermore, Nts and Hcrt neurons consolidate wakefulness while Mch neurons promote sleep. The physiological relevance of chromosomal dynamics, and the balance between DNA damage and repair in the Mch-Nts-Hcrt circuit is linked to sleep and wake states.