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Field: Biology/Life Science Session Topic: Optogenetics: Manifold Applications Speaker: Akihiro YAMANAKA, National Institute for Physiological Sciences (NIPS) 1. Introduction We spend almost one third of our life time just to sleep. Sleep/wakefulness cycle is a very intriguing physiological phenomenon. We fall asleep at least once per day. After sleeping for a while, we can wake up naturally. However, the mechanism regulating sleep/wakefulness cycle has not been completely understood so far, while it appears to be regulated by neurons in the hypothalamus. Orexin, also called hypocretin is a neuropeptide recently identified as a natural ligand for orphan G protein coupled receptor1. Orexin-producing neurons (orexin neurons) are located specifically in the hypothalamus but project their efferents throughout the brain. Intriguingly, the mice lacking prepro-orexin gene showed behavioral characteristics similar to human sleep disorder “Narcolepsy”, that is a fragmentation of sleep/wakefulness and sudden muscle weakness. Human clinical studies also showed that orexin neurons are specifically ablated in the narcoleptic patient’s brain. These results suggest that the orexin neurons play a critical role in the regulation of sleep/wakefulness. Previous studies using electrophysiological in vitro techniques have identified potential neuronal pathways or networks connecting orexin neurons with other neurons which are known to be involved in sleep/ wakefulness regulation2,3. However, it will be essential to analyze living animals for the purpose of elucidating how these neuronal networks regulate sleep/wakefulness, a physiological phenomenon only observed in living animals. To address this, we incorporated recently developed technique “optogenetics”4, which allows us to control neuron activity by illuminating light locally in the brain. In this symposium, I will discuss physiological importance of the activity of orexin neurons in the maintenance of arousal using optogenetics. References 1. 2. 3. 4. Sakurai, T. et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573-85 (1998). Yamanaka, A. et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38, 701-13 (2003). Yamanaka, A. & Tsunematsu, T. New approaches for the study of orexin function. J Neuroendocrinol 22, 818-24 (2010). Boyden, E.S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neuroscience 8, 1263-1268 (2005).