Tuning arousal with optogenetic modulation of locus coeruleus neurons
Matthew E Carter, Ofer Yizhar, Sachiko Chikahisa, Hieu Nguyen, Antoine Adamantidis, Seiji Nishino, Karl Deisseroth, Luis de Lecea, Matthew E Carter, Ofer Yizhar, Sachiko Chikahisa, Hieu Nguyen, Antoine Adamantidis, Seiji Nishino, Karl Deisseroth, Luis de Lecea
Abstract
Neural activity in the noradrenergic locus coeruleus correlates with periods of wakefulness and arousal. However, it is unclear whether tonic or phasic activity in these neurons is necessary or sufficient to induce transitions between behavioral states and to promote long-term arousal. Using optogenetic tools in mice, we found that there is a frequency-dependent, causal relationship among locus coeruleus firing, cortical activity, sleep-to-wake transitions and general locomotor arousal. We also found that sustained, high-frequency stimulation of the locus coeruleus at frequencies of 5 Hz and above caused reversible behavioral arrests. These results suggest that the locus coeruleus is finely tuned to regulate organismal arousal and that bursts of noradrenergic overexcitation cause behavioral attacks that resemble those seen in people with neuropsychiatric disorders.
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References
- Aston-Jones G, Cohen JD. An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu. Rev. Neurosci. 2005;28:403–450.
- Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res. Rev. 2003;42:33–84.
- Foote SL, Bloom FE, Aston-Jones G. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol. Rev. 1983;63:844–914.
- Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhyhms. Nature. 2005;437:1257–1263.
- Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nature Rev. Neurosci. 2009;10:211–223.
- Aston-Jones G, Bloom FE. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J. Neurosci. 1981;1:876–886.
- Aston-Jones G, Bloom FE. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. J. Neurosci. 1981;1:887–900.
- Hobson JA, McCarley RW, Wyzinski PW. Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science. 1975;189:55–58.
- Foote SL, Aston-Jones G, Bloom FE. Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc. Natl. Acad. Sci. 1980;77:3033–3037.
- Jones BE, Harper ST, Halaris AE. Effects of locus coeruleus lesions upon cerebral monoamine content, sleep-wakefulness states and the response to amphetamine in the cat. Brain Res. 1977;124:473–496.
- Lidbrink P. The effect of lesions of ascending noradrenaline pathways on sleep and waking in the rat. Brain Res. 1974;74:19–40.
- Blanco-Centurion C, Gerashchenko D, Shiromani PJ. Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J. Neurosci. 2007;27:14041–14048.
- Hunsley MS, Palmiter RD. Norepinephrine-deficient mice exhibit normal sleep-wake states but have shorter sleep latency after mild stress and low doses of amphetamine. Sleep. 2003;26:521–526.
- Berridge CW, Espana RA. Synergistic sedative effects of noradrenergic alpha(1)- and beta-receptor blockade on forebrain electroencephalographic and behavioral indices. Neuroscience. 2000;99:495–505.
- De Sarro GB, Ascioti C, Froio F, Libri V, Nistico F. Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha 1- and alpha 2-adrenoceptors affect sleep and arousal mechanisms. Br. J. Pharmacol. 1987;90:675–685.
- Flicker C, Geyer MA. The hippocampus as a possible site of action for increased locomotion during intracerebral infusions of norepinephrine. Behav. Neural Biol. 1982;34:421–426.
- Segal DS, Mandell AJ. Behavioral activation of rats during intraventricular infusion of norepinephrine. Proc. Natl. Acad. Sci. U.S.A. 1970;66:289–293.
- Berridge CW, Foote SL. Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus. J. Neurosci. 1991;11:3135–3145.
- Gradinaru V, et al. Targeting and readout strategies for fast optical neural control in vitro and in vivo. J. Neurosci. 2007;27:14231–14238.
- Zhang F, Aravanis AM, Adamantidis A, de Lecea L, Deisseroth K. Circuit-breakers: optical technologies for probing neural signals and systems. Nature Rev. Neurosci. 2007;8:577–581.
- Adamantidis A, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature. 2007;450:420–424.
- Carter ME, Adamantidis A, Ohtsu H, Deisseroth K, de Lecea L. Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J. Neurosci. 2009;29:10939–10949.
- Gradinaru V, Thompson KR, Deisseroth K. eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications. Brain Cell Biol. 2008;36:129–139.
- Zhang F, et al. Multimodal fast optical interrogation of neural circuitry. Nature. 2007;446:633–639.
- Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 2005;8:1263–1268.
- Sohal VS, Zhang F, Yizhar O, Deisseroth K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature. 2009;459:698–702.
- Tsai HC, et al. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009;324:1080–1084.
- Lindeberg J, et al. Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus. Genesis. 2004;40:67–73.
- Paxinos G, Franklin K. The Mouse Brain in Stereotaxic Coordinates. ed. 2 Academic Press; New York: p. 2001.
- Shipley MT, et al. Dendrites of locus coeruleus neurons extend preferentially into two pericoerulear zones. J. Comp. Neurol. 1996;365:56–68.
- Bourgin P, et al. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J. Neurosci. 2000;20:7760–7765.
- Valentino R, et al. Corticotropin-releasing factor innervation of the locus coeruleus region: distribution of fibers and sources of input. Neuroscience. 1992;48:689–705.
- van Bockstaele EJ, et al. Anatomic basis for differential regulation of the rostrolateral peri-locus coeruleus region by limbic afferents. Biol Psychiatry. 1999;46:1352–1363.
- Jodo E, Chiang C, Aston-Jones G. Potent excitatory influence of prefrontal cortex activity on noradrenergic locus coreuleus neurons. Neuroscience. 1998;83:63–79.
- Luquet S, Perez FA, Hnasko TS, Palmiter RD. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science. 2005;310:683–685.
- Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell. 2009;137:1225–1234.
- Szot P, et al. A comprehensive analysis of the effect of DSP4 on the locus coeruleus noradrenergic system in the rat. Neuropharmacology. 2010;166:279–291.
- Parmentier R, et al. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci. 2002;22:7695–7711.
- McGinty DJ, Harper RM. Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res. 1976;101:569–575.
- Steriade M. Acetycholine systems and rhythmic activities during the waking—sleep cycle. Prog. Brain Res. 2004;145:179–196.
- Boucetta S, Jones BE. Activity profiles of cholinergic and intermingled GABAergic and putative glutamatergic neurons in the pontomesencelphalic tegmentum of urethane-anesthetized rats. J. Neurosci. 2009;29:4664–4674.
- Hassani OK, Lee MG, Henny P, Jones BE. Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep-wake cycle. J. Neurosci. 2009;29:11828–11840.
- Arnsten A. Stress signaling pathways that impair prefrontal cortex structure and function. Nat. Rev. Neurosci. 2009;10:410–422.
- Ramos B, Arnsten A. Adrenergic pharmacology and cognition: Focus on the prefrontal cortex. Pharmacol. Ther. 2006;113:523–536.
- Bouret S, Sara SJ. Network reset: a simplified overarching theory of locus coeruleus noradrenaline function. Trends Neurosci. 2005;28:574–582.
- Wu MF, et al. Activity of dorsal raphe cells across the sleep-waking cycle and during cataplexy in narcoleptic dogs. J. Physiol. 2004;554:202–215.
- Lai YY, Kodama T, Siegel JM. Changes in monoamine release in the ventral horn and hypoglossal nucleus linked to pontine inhibition of muscle tone: an in vivo microdialysis study. J. Neurosci. 2001;21:7384–7391.
- Kodama T, Lai YY, Siegel JM. Changes in inhibitory amino acid release linked to pontine-induced atonia: an in vivo microdialysis study. J. Neurosci. 2003;23:1548–1554.
- Scammell TE, et al. A consensus definition of cataplexy in mouse models of narcolepsy. Sleep. 2009;32:111–116.
- Wu MF, et al. Locus coeruleus neurons: cessation of activity during cataplexy. Neuroscience. 1999;91:1389–1399.
Source: PubMed