Abstract
The mechanisms of instinctive behaviors such as feeding, drinking, sexual activity and sleep/wakefulness can only be studied in the whole animal with intact neural networks. This has been difficult due to lack of techniques to control the activity of specific neurons in intact animals. Optogenetics is a recent technique, which enables such control using light and allows the study of regulatory mechanisms of instinctive behaviors. In this section, we introduce how optogenetics was applied to orexin/hypocretin neurons to reveal the regulatory mechanisms of sleep and wakefulness. Activity manipulation of orexin neurons controls the state changes among wakefulness, non-rapid eye movement (NREM) sleep and REM sleep state. Selective activation of orexin neurons using channelrhodopsin-2 (ChR2) or melanopsin (OPN4) induced transition from sleep to wakefulness. In contrast, suppression of these neurons using halorhodopsin (HaloR) or archaerhodopsin (ArchR) induced transition from wakefulness to NREM sleep and increased the time spent in NREM sleep. These studies help answer how orexin neurons contribute to regulate sleep/wakefulness.
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References
Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L (2007) Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450(7168):420–424. doi:10.1038/nature06310
Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268. doi:10.1038/nn1525
Brown RE, Sergeeva OA, Eriksson KS, Haas HL (2002) Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J Neurosci: Official J Soc Neurosci 22(20):8850–8859
Carter ME, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S, Deisseroth K, de Lecea L (2010) Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci 13(12):1526–1533. doi:10.1038/nn.2682
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98(4):437–451
Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden ES (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463(7277):98–102. doi:10.1038/nature08652
Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami K, Goto K, Yanagisawa M, Sakurai T (2001) Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30(2):345–354
Liu RJ, van den Pol AN, Aghajanian GK (2002) Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. J Neurosci: Official J Soc Neurosci 22(21):9453–9464
Mileykovskiy BY, Kiyashchenko LI, Siegel JM (2005) Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46(5):787–798. doi:10.1016/j.neuron.2005.04.035
Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000) Hypocretin (orexin) deficiency in human narcolepsy. Lancet 355(9197):39–40. doi:10.1016/s0140-6736(99)05582-8
Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E (2000) A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6(9):991–997. doi:10.1038/79690
Rechtschaffen A, Gilliland MA, Bergmann BM, Winter JB (1983) Physiological correlates of prolonged sleep deprivation in rats. Science 221(4606):182–184
Tsunematsu T, Kilduff TS, Boyden ES, Takahashi S, Tominaga M, Yamanaka A (2011) Acute optogenetic silencing of orexin/hypocretin neurons induces slow-wave sleep in mice. J Neurosci: the official journal of the Society for Neuroscience 31(29):10529–10539. doi:10.1523/JNEUROSCI.0784-11.2011
Tsunematsu T, Tanaka KF, Yamanaka A, Koizumi A (2012) Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of wakefulness of mice in vivo by blue light. Neurosci Res. doi:10.1016/j.neures.2012.07.005
Tsunematsu T, Tabuchi S, Tanaka KF, Boyden ES, Tominaga M, Yamanaka A (2013) Long-lasting silencing of orexin/hypocretin neurons using archaerhodopsin induces slow-wave sleep in mice. Behav Brain Res 255:64–74. doi:10.1016/j.bbr.2013.05.021
Willie JT, Chemelli RM, Sinton CM, Tokita S, Williams SC, Kisanuki YY, Marcus JN, Lee C, Elmquist JK, Kohlmeier KA, Leonard CS, Richardson JA, Hammer RE, Yanagisawa M (2003) Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron 38(5):715–730
Yamanaka A, Tsujino N, Funahashi H, Honda K, Guan JL, Wang QP, Tominaga M, Goto K, Shioda S, Sakurai T (2002) Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem Biophys Res Commun 290(4):1237–1245. doi:10.1006/bbrc.2001.6318
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Yamanaka, A., Tsunematsu, T. (2015). Elucidation of Neuronal Circuitry Involved in the Regulation of Sleep/Wakefulness Using Optogenetics. In: Sakurai, T., Pandi-Perumal, S., Monti, J. (eds) Orexin and Sleep. Springer, Cham. https://doi.org/10.1007/978-3-319-23078-8_6
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DOI: https://doi.org/10.1007/978-3-319-23078-8_6
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