Advertisement

Optogenetics pp 391-406 | Cite as

Elucidation of Neural Circuits Involved in the Regulation of Sleep/Wakefulness Using Optogenetics

Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1293)

Abstract

Although sleep is an absolutely essential physiological phenomenon for maintaining normal health in animals, little is known about its function to date. In this section, I introduce the application of optogenetics to freely behaving animals for the purpose of characterizing neural circuits involved in the regulation of sleep/wakefulness. Applying optogenetics to the specific neurons involved in sleep/wakefulness regulation enabled the precise control of the sleep/wakefulness states between wakefulness, non-rapid eye movement (NREM) sleep, and REM sleep states. For example, selective activation of orexin neurons using channelrhodopsin-2 and melanopsin induced a transition from sleep to wakefulness. In contrast, suppression of these neurons using halorhodopsin and archaerhodopsin induced a transition from wakefulness to NREM sleep and increased the time spent in NREM sleep. Selective activation of melanin-concentrating hormone (MCH) neurons induced a transition from NREM sleep to REM sleep and prolonged the time spent in REM sleep, which was accompanied by a decrease in NREM sleep time. Optogenetics was first introduced to orexin neurons in 2007 and has since rapidly spread throughout the field of neuroscience. In the last 13 years or so, neural nuclei and the cell types that control sleep/wakefulness have been identified. The use of optogenetic studies has greatly contributed to the elucidation of the neural circuits involved in the regulation of sleep/wakefulness.

Keywords

Orexin Melanin-concentrating hormone Wakefulness Non-rapid eye movement (NREM) sleep Rapid eye movement (REM) sleep 

Abbreviations

AAV

Adeno-associated virus

ArchR

Archaerhodopsin-3

ArchT

Archaerhodopsin TP009

ChR2

Channelrhodopsin-2

dDpMe

Deep mesencephalic nucleus

DR

Dorsal raphe

EEGs

Electroencephalograms

EMGs

Electromyograms

GPCR

G Protein-coupled receptor

HaloR

Halorhodopsin

LC

Locus coeruleus

LDT

Laterodorsal tegmental nucleus

MCH

Melanin-concentrating hormone

MnPO

Median preoptic nucleus

NA

Numerical aperture

NREM

Non-rapid eye movement

OPN4

Melanopsin

OX1R

Orexin 1 receptor

OX2R

Orexin 2 receptor

PAG

Periaqueductal gray

PBN

Parabrachial nucleus

PPT

Pedunculopontine tegmental nucleus

REM

Rapid eye movement

SLD

Sublaterodorsal nucleus

TMN

Tuberomammillary nucleus

VLPO

Ventrolateral preoptic area

This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

T.T. is supported by PRESTO from JST (JPMJPR1887), JSPS Grant-in-Aid for Research Activity Start-up (17H06520), and JSPS Grant-in-Aid for Scientific Research on Innovative Areas (20H05047).

References

  1. 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):420–424CrossRefPubMedPubMedCentralGoogle Scholar
  2. Anaclet C, Ferrari L, Arrigoni E, Bass CE, Saper CB, Lu J, Fuller PM (2014) The GABAergic parafacial zone is a medullary slow wave sleep–promoting center. Nat Neurosci 17(9):1217–1224CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bellesi M, de Vivo L, Tononi G, Cirelli C (2015) Effects of sleep and wake on astrocytes: clues from molecular and ultrastructural studies. BMC Biol 13:66CrossRefPubMedPubMedCentralGoogle Scholar
  4. Boyce R, Glasgow SD, Williams S (2016) Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation. Science 352:812–816CrossRefPubMedGoogle Scholar
  5. 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 13:1526–1533CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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 98:437–451CrossRefPubMedGoogle Scholar
  7. Foote SL, Aston-Jones G, Bloom FE (1980) Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc Natl Acad Sci U S A 77(5):3033–3037CrossRefPubMedPubMedCentralGoogle Scholar
  8. Ghandour K, Ohkawa N, Fung CCA, Asai H, Saitoh Y, Takekawa T, Okubo-Suzuki R, Soya S, Nishizono H, Matsuo M, Osanai M, Sato M, Ohkura M, Nakai J, Hayashi Y, Sakurai T, Kitamura T, Fukai T, Inokuchi K (2019) Orchestrated ensemble activities constitute a hippocampal memory engram. Nat Commun 10(1):2637CrossRefPubMedPubMedCentralGoogle Scholar
  9. Halassa MM, Florian C, Fellin T, Munoz JR, Abel T, Haydon PG, Frank MG (2009) Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron 61:213–219CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hara J, Beuckmann CT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yagami KI, Goto K, Yanagisawa M, Sakurai T (2001) Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron 30:345–354CrossRefPubMedGoogle Scholar
  11. Hobson JA, McCarley RW, Wyzinski PW (1975) Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 189:55–58CrossRefPubMedGoogle Scholar
  12. Irmak SO, de Lecea L (2014) Basal forebrain cholinergic modulation of sleep transitions. Sleep 37(12):1941–1951CrossRefPubMedGoogle Scholar
  13. Ito H, Yanase M, Yamashita A, Kitabatake C, Hamada A, Suhara Y, Narita M, Ikegami D, Sakai H, Yamazaki M, Narita M (2013) Analysis of sleep disorders under pain using an optogenetic tool: possible involvement of the activation of dorsal raphe nucleus-serotonergic neurons. Mol Brain 6:59CrossRefPubMedPubMedCentralGoogle Scholar
  14. Izawa S, Chowdhury S, Miyazaki T, Mukai Y, Ono D, Inoue R, Ohmura Y, Mizoguchi H, Kimura K, Yoshioka M, Terao A, Kilduff TS, Yamanaka A (2019) REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories. Science 365(6459):1308–1313CrossRefPubMedPubMedCentralGoogle Scholar
  15. Jego S, Glasgow SD, Herrera CG, Ekstrand M, Reed SJ, Boyce R, Friedman J, Burdakov D, Adamantidis AR (2013) Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat Neurosci 16(11):1637–1643CrossRefPubMedPubMedCentralGoogle Scholar
  16. Krenzer M, Anaclet C, Vetrivelan R, Wang N, Vong L, Lowell BB, Fuller PM, Lu J (2011) Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia. PLoS One 6(10):e24998CrossRefPubMedPubMedCentralGoogle Scholar
  17. Miyamoto D, Hirai D, Fung CCA, Inutsuka A, Odagawa M, Suzuki T, Boehringer R, Adaikkan C, Matsubara C, Matsuki N, Fukai T, Mchugh TJ, Yamanaka A, Murayama M (2016) Top-down cortical input during NREM sleep consolidates perceptual memory. Science 352:1315–1318CrossRefPubMedGoogle Scholar
  18. 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 6:991–997CrossRefPubMedGoogle Scholar
  19. Portas CM, Bjorvatn B, Fagerland S, Gronli J, Mundal V, Sorensen E, Ursin R (1998) On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat. Neuroscience 83(3):807–814CrossRefPubMedGoogle Scholar
  20. Rechtschaffen A, Gilliland MA, Bergmann BM, Winter JB (1983) Physiological correlates of prolonged sleep deprivation in rats. Science 221:182–184CrossRefPubMedGoogle Scholar
  21. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, Mcnulty DE, Liu W-s, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585CrossRefPubMedGoogle Scholar
  22. Szymusiak R, Iriye T, McGinty D (1989) Sleep-waking discharge of neurons in the posterior lateral hypothalamic area of cats. Brain Res Bull 23(1–2):111–120CrossRefPubMedGoogle Scholar
  23. Tabuchi S, Tsunematsu T, Black SW, Tominaga M, Maruyama M, Takagi K, Minokoshi Y, Sakurai T, Kilduff TS, Yamanaka A (2014) Conditional ablation of orexin/hypocretin neurons: a new mouse model for the study of narcolepsy and orexin system function. J Neurosci 34:6495–6509CrossRefPubMedPubMedCentralGoogle Scholar
  24. Trulson ME, Jacobs BL (1979) Raphe unit activity in freely moving cats: correlation with level of behavioral arousal. Brain Res 163(1):135–150CrossRefPubMedGoogle Scholar
  25. Tsunematsu T, Fu L-Y, Yamanaka A, Ichiki K, Tanoue A, Sakurai T, van den Pol AN (2008) Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: implications for water homeostasis. J Neurosci 28:228–238CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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 31(29):10529–10539CrossRefPubMedPubMedCentralGoogle Scholar
  27. Tsunematsu T, Tabuchi S, Tanaka KF, Boyden ES, Tominaga M, Yamanaka A (2013a) Long-lasting silencing of orexin/hypocretin neurons using archaerhodopsin induces slow-wave sleep in mice. Behav Brain Res 255:64–74CrossRefPubMedGoogle Scholar
  28. Tsunematsu T, Tanaka KF, Yamanaka A, Koizumi A (2013b) Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of wakefulness of mice in vivo by blue light. Neurosci Res 75:23–28CrossRefPubMedPubMedCentralGoogle Scholar
  29. Tsunematsu T, Ueno T, Tabuchi S, Inutsuka A, Tanaka KF, Hasuwa H, Kilduff TS, Terao A, Yamanaka A (2014) Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. J Neurosci 34(20):6896–6909CrossRefPubMedPubMedCentralGoogle Scholar
  30. Williams RH, Tsunematsu T, Thomas AM, Bogyo K, Yamanaka A, Kilduff TS (2019) Transgenic archaerhodopsin-3 expression in hypocretin/orexin neurons engenders cellular dysfunction and features of type 2 narcolepsy. J Neurosci 39(47):9435–9452CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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 38:715–730CrossRefPubMedGoogle Scholar
  32. Xu M, Chung S, Zhang S, Zhong P, Ma C, Chang W-C, Weissbourd B, Sakai N, Luo L, Nishino S, Dan Y (2015) Basal forebrain circuit for sleep-wake control. Nat Neurosci 18:1641–1647CrossRefPubMedPubMedCentralGoogle Scholar
  33. Yamanaka A (2012) Optogenetical approach to control the activity of specific types of neurons in vivo. Nihon Yakurigaku Zasshi 140(6):280–284CrossRefPubMedGoogle Scholar
  34. Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami KI, Sugiyama F, Goto K, Yanagisawa M, Sakurai T (2003) Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron 38:701–713CrossRefPubMedGoogle Scholar
  35. Yu X, Ye Z, Houston CM, Zecharia AY, Ma Y, Zhang Z, Uygun DS, Parker S, Vyssotski AL, Yustos R, Franks NP, Brickley SG, Wisden W (2015) Wakefulness is governed by GABA and histamine cotransmission. Neuron 87:1–15CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2021

Authors and Affiliations

  1. 1.Graduate School of Life SciencesTohoku UniversitySendaiJapan
  2. 2.Frontier Research Institute for Interdisciplinary SciencesTohoku UniversitySendaiJapan
  3. 3.JST, PRESTOKawaguchiJapan

Personalised recommendations

Cite chapter

Buy options