Recurrent Circuitry for Balancing Sleep Need and Sleep

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2018 Jan 9

PMID 29307711

Citations 86

Authors

Jeffrey M Donlea

Diogo Pimentel

Clifford B Talbot

Anissa Kempf

Jaison J Omoto

Volker Hartenstein

Gero Miesenbock

Affiliations

Soon will be listed here.

Abstract

Sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila are integral to sleep homeostasis, but how these cells impose sleep on the organism is unknown. We report that dFB neurons communicate via inhibitory transmitters, including allatostatin-A (AstA), with interneurons connecting the superior arch with the ellipsoid body of the central complex. These "helicon cells" express the galanin receptor homolog AstA-R1, respond to visual input, gate locomotion, and are inhibited by AstA, suggesting that dFB neurons promote rest by suppressing visually guided movement. Sleep changes caused by enhanced or diminished allatostatinergic transmission from dFB neurons and by inhibition or optogenetic stimulation of helicon cells support this notion. Helicon cells provide excitation to R2 neurons of the ellipsoid body, whose activity-dependent plasticity signals rising sleep pressure to the dFB. By virtue of this autoregulatory loop, dFB-mediated inhibition interrupts processes that incur a sleep debt, allowing restorative sleep to rebalance the books. VIDEO ABSTRACT.

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References

Rodan A, Kiger Jr J, Heberlein U . Functional dissection of neuroanatomical loci regulating ethanol sensitivity in Drosophila. J Neurosci. 2002; 22(21):9490-501. PMC: 6758036. View

Ilius M, Wolf R, Heisenberg M . The central complex of Drosophila melanogaster is involved in flight control: studies on mutants and mosaics of the gene ellipsoid body open. J Neurogenet. 1994; 9(3):189-206. DOI: 10.3109/01677069409167279. View

Smith K, Walker M, Artymyshyn R, Bard J, Borowsky B, Tamm J . Cloned human and rat galanin GALR3 receptors. Pharmacology and activation of G-protein inwardly rectifying K+ channels. J Biol Chem. 1998; 273(36):23321-6. DOI: 10.1074/jbc.273.36.23321. View

Klapoetke N, Murata Y, Kim S, Pulver S, Birdsey-Benson A, Cho Y . Independent optical excitation of distinct neural populations. Nat Methods. 2014; 11(3):338-46. PMC: 3943671. DOI: 10.1038/nmeth.2836. View

Saper C, Cano G, Scammell T . Homeostatic, circadian, and emotional regulation of sleep. J Comp Neurol. 2005; 493(1):92-8. DOI: 10.1002/cne.20770. View

Shaw P, Tononi G, Greenspan R, Robinson D . Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature. 2002; 417(6886):287-91. DOI: 10.1038/417287a. View

Schmid B, Helfrich-Forster C, Yoshii T . A new ImageJ plug-in "ActogramJ" for chronobiological analyses. J Biol Rhythms. 2011; 26(5):464-7. DOI: 10.1177/0748730411414264. View

Brown R, Basheer R, McKenna J, Strecker R, McCarley R . Control of sleep and wakefulness. Physiol Rev. 2012; 92(3):1087-187. PMC: 3621793. DOI: 10.1152/physrev.00032.2011. View

Minke B, Kirschfeld K . The contribution of a sensitizing pigment to the photosensitivity spectra of fly rhodopsin and metarhodopsin. J Gen Physiol. 1979; 73(5):517-40. PMC: 2215190. DOI: 10.1085/jgp.73.5.517. View

10.

Jenett A, Rubin G, Ngo T, Shepherd D, Murphy C, Dionne H . A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012; 2(4):991-1001. PMC: 3515021. DOI: 10.1016/j.celrep.2012.09.011. View

11.

Owald D, Fouquet W, Schmidt M, Wichmann C, Mertel S, Depner H . A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila. J Cell Biol. 2010; 188(4):565-79. PMC: 2828917. DOI: 10.1083/jcb.200908055. View

12.

Lebestky T, Chang J, Dankert H, Zelnik L, Kim Y, Han K . Two different forms of arousal in Drosophila are oppositely regulated by the dopamine D1 receptor ortholog DopR via distinct neural circuits. Neuron. 2009; 64(4):522-36. PMC: 2908595. DOI: 10.1016/j.neuron.2009.09.031. View

13.

Dietzl G, Chen D, Schnorrer F, Su K, Barinova Y, Fellner M . A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature. 2007; 448(7150):151-6. DOI: 10.1038/nature05954. View

14.

Venken K, Schulze K, Haelterman N, Pan H, He Y, Evans-Holm M . MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat Methods. 2011; 8(9):737-43. PMC: 3191940. DOI: 10.1038/nmeth.1662. View

15.

Tononi G, Cirelli C . Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull. 2003; 62(2):143-50. DOI: 10.1016/j.brainresbull.2003.09.004. View

16.

Huang Y, Ainsley J, Reijmers L, Jackson F . Translational profiling of clock cells reveals circadianly synchronized protein synthesis. PLoS Biol. 2013; 11(11):e1001703. PMC: 3864454. DOI: 10.1371/journal.pbio.1001703. View

17.

Sherin J, Elmquist J, Torrealba F, Saper C . Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat. J Neurosci. 1998; 18(12):4705-21. PMC: 6792696. View

18.

Neuser K, Triphan T, Mronz M, Poeck B, Strauss R . Analysis of a spatial orientation memory in Drosophila. Nature. 2008; 453(7199):1244-7. DOI: 10.1038/nature07003. View

19.

Zemelman B, Lee G, Ng M, Miesenbock G . Selective photostimulation of genetically chARGed neurons. Neuron. 2002; 33(1):15-22. DOI: 10.1016/s0896-6273(01)00574-8. View

20.

Chou T, Bjorkum A, Gaus S, Lu J, Scammell T, Saper C . Afferents to the ventrolateral preoptic nucleus. J Neurosci. 2002; 22(3):977-90. PMC: 6758527. View