Functional Wiring of Hypocretin and LC-NE Neurons: Implications for Arousal

Overview

Journal Front Behav Neurosci

Specialty Psychology

Date 2013 Jun 5

PMID 23730276

Citations 30

Authors

Matthew E Carter

Luis De Lecea

Antoine Adamantidis

Affiliations

Soon will be listed here.

Abstract

To survive in a rapidly changing environment, animals must sense their external world and internal physiological state and properly regulate levels of arousal. Levels of arousal that are abnormally high may result in inefficient use of internal energy stores and unfocused attention to salient environmental stimuli. Alternatively, levels of arousal that are abnormally low may result in the inability to properly seek food, water, sexual partners, and other factors necessary for life. In the brain, neurons that express hypocretin neuropeptides may be uniquely posed to sense the external and internal state of the animal and tune arousal state according to behavioral needs. In recent years, we have applied temporally precise optogenetic techniques to study the role of these neurons and their downstream connections in regulating arousal. In particular, we have found that noradrenergic neurons in the brainstem locus coeruleus (LC) are particularly important for mediating the effects of hypocretin neurons on arousal. Here, we discuss our recent results and consider the implications of the anatomical connectivity of these neurons in regulating the arousal state of an organism across various states of sleep and wakefulness.

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References

Aston-Jones G, Bloom F . Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci. 1981; 1(8):876-86. PMC: 6564235. View

Thannickal T, Moore R, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M . Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000; 27(3):469-74. PMC: 8760623. DOI: 10.1016/s0896-6273(00)00058-1. View

Miesenbock G . The optogenetic catechism. Science. 2009; 326(5951):395-9. DOI: 10.1126/science.1174520. View

Adamantidis A, Thomas E, Foidart A, Tyhon A, Coumans B, Minet A . Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function. Eur J Neurosci. 2005; 21(10):2837-44. DOI: 10.1111/j.1460-9568.2005.04100.x. View

Lidbrink P . The effect of lesions of ascending noradrenaline pathways on sleep and waking in the rat. Brain Res. 1974; 74(1):19-40. DOI: 10.1016/0006-8993(74)90109-7. View

Itoi K, Sugimoto N . The brainstem noradrenergic systems in stress, anxiety and depression. J Neuroendocrinol. 2010; 22(5):355-61. DOI: 10.1111/j.1365-2826.2010.01988.x. View

Dong S, Rogan S, Roth B . Directed molecular evolution of DREADDs: a generic approach to creating next-generation RASSLs. Nat Protoc. 2010; 5(3):561-73. DOI: 10.1038/nprot.2009.239. View

Blanco-Centurion C, Liu M, Konadhode R, Pelluru D, Shiromani P . Effects of orexin gene transfer in the dorsolateral pons in orexin knockout mice. Sleep. 2013; 36(1):31-40. PMC: 3524540. DOI: 10.5665/sleep.2296. View

Trivedi P, Yu H, MacNeil D, Van der Ploeg L, Guan X . Distribution of orexin receptor mRNA in the rat brain. FEBS Lett. 1998; 438(1-2):71-5. DOI: 10.1016/s0014-5793(98)01266-6. View

10.

Blanco-Centurion C, Gerashchenko D, Shiromani P . Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci. 2007; 27(51):14041-8. PMC: 2975593. DOI: 10.1523/JNEUROSCI.3217-07.2007. View

11.

Carter M, Yizhar O, Chikahisa S, Nguyen H, Adamantidis A, Nishino S . Tuning arousal with optogenetic modulation of locus coeruleus neurons. Nat Neurosci. 2010; 13(12):1526-33. PMC: 3174240. DOI: 10.1038/nn.2682. View

12.

Aravanis A, Wang L, Zhang F, Meltzer L, Mogri M, Schneider M . An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng. 2007; 4(3):S143-56. DOI: 10.1088/1741-2560/4/3/S02. View

13.

Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y . A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000; 6(9):991-7. DOI: 10.1038/79690. View

14.

Tsai H, Zhang F, Adamantidis A, Stuber G, Bonci A, De Lecea L . Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009; 324(5930):1080-4. PMC: 5262197. DOI: 10.1126/science.1168878. View

15.

Berndt A, Yizhar O, Gunaydin L, Hegemann P, Deisseroth K . Bi-stable neural state switches. Nat Neurosci. 2008; 12(2):229-34. DOI: 10.1038/nn.2247. View

16.

Zhang F, Wang L, Boyden E, Deisseroth K . Channelrhodopsin-2 and optical control of excitable cells. Nat Methods. 2006; 3(10):785-92. DOI: 10.1038/nmeth936. View

17.

Zhang F, Gradinaru V, Adamantidis A, Durand R, Airan R, De Lecea L . Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat Protoc. 2010; 5(3):439-56. PMC: 4503465. DOI: 10.1038/nprot.2009.226. View

18.

Wu M, John J, Boehmer L, Yau D, Nguyen G, Siegel J . Activity of dorsal raphe cells across the sleep-waking cycle and during cataplexy in narcoleptic dogs. J Physiol. 2003; 554(Pt 1):202-15. PMC: 1664742. DOI: 10.1113/jphysiol.2003.052134. View

19.

Carter M, Adamantidis A, Ohtsu H, Deisseroth K, De Lecea L . Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J Neurosci. 2009; 29(35):10939-49. PMC: 3849591. DOI: 10.1523/JNEUROSCI.1205-09.2009. View

20.

Yizhar O, Fenno L, Davidson T, Mogri M, Deisseroth K . Optogenetics in neural systems. Neuron. 2011; 71(1):9-34. DOI: 10.1016/j.neuron.2011.06.004. View