Caffeine promotes wakefulness via dopamine signaling in Drosophila
Identifieur interne : 000187 ( Pmc/Curation ); précédent : 000186; suivant : 000188Caffeine promotes wakefulness via dopamine signaling in Drosophila
Auteurs : Aleksandra H. Nall [États-Unis] ; Iryna Shakhmantsir [États-Unis] ; Karol Cichewicz [États-Unis] ; Serge Birman [France] ; Jay Hirsh [États-Unis] ; Amita Sehgal [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly
Url:
DOI: 10.1038/srep20938
PubMed: 26868675
PubMed Central: 4751479
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Caffeine promotes wakefulness via dopamine signaling in <italic>Drosophila</italic></title><author><name sortKey="Nall, Aleksandra H" sort="Nall, Aleksandra H" uniqKey="Nall A" first="Aleksandra H." last="Nall">Aleksandra H. Nall</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shakhmantsir, Iryna" sort="Shakhmantsir, Iryna" uniqKey="Shakhmantsir I" first="Iryna" last="Shakhmantsir">Iryna Shakhmantsir</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cichewicz, Karol" sort="Cichewicz, Karol" uniqKey="Cichewicz K" first="Karol" last="Cichewicz">Karol Cichewicz</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biology, University of Virginia</institution>, Charlottesville, VA 22904,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Birman, Serge" sort="Birman, Serge" uniqKey="Birman S" first="Serge" last="Birman">Serge Birman</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Genes Circuits Rhythms and Neuropathologies, Brain Plasticity Unit, CNRS, PSL Research University</institution>, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hirsh, Jay" sort="Hirsh, Jay" uniqKey="Hirsh J" first="Jay" last="Hirsh">Jay Hirsh</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biology, University of Virginia</institution>, Charlottesville, VA 22904,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sehgal, Amita" sort="Sehgal, Amita" uniqKey="Sehgal A" first="Amita" last="Sehgal">Amita Sehgal</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26868675</idno><idno type="pmc">4751479</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751479</idno><idno type="RBID">PMC:4751479</idno><idno type="doi">10.1038/srep20938</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000188</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000188</idno><idno type="wicri:Area/Pmc/Curation">000187</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000187</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Caffeine promotes wakefulness via dopamine signaling in <italic>Drosophila</italic></title><author><name sortKey="Nall, Aleksandra H" sort="Nall, Aleksandra H" uniqKey="Nall A" first="Aleksandra H." last="Nall">Aleksandra H. Nall</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shakhmantsir, Iryna" sort="Shakhmantsir, Iryna" uniqKey="Shakhmantsir I" first="Iryna" last="Shakhmantsir">Iryna Shakhmantsir</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cichewicz, Karol" sort="Cichewicz, Karol" uniqKey="Cichewicz K" first="Karol" last="Cichewicz">Karol Cichewicz</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biology, University of Virginia</institution>, Charlottesville, VA 22904,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Birman, Serge" sort="Birman, Serge" uniqKey="Birman S" first="Serge" last="Birman">Serge Birman</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Genes Circuits Rhythms and Neuropathologies, Brain Plasticity Unit, CNRS, PSL Research University</institution>, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hirsh, Jay" sort="Hirsh, Jay" uniqKey="Hirsh J" first="Jay" last="Hirsh">Jay Hirsh</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Biology, University of Virginia</institution>, Charlottesville, VA 22904,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sehgal, Amita" sort="Sehgal, Amita" uniqKey="Sehgal A" first="Amita" last="Sehgal">Amita Sehgal</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly <italic>Drosophila melanogaster</italic>, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Penetar, D" uniqKey="Penetar D">D. Penetar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alhaider, I A" uniqKey="Alhaider I">I. A. Alhaider</name></author><author><name sortKey="Aleisa, A M" uniqKey="Aleisa A">A. M. Aleisa</name></author><author><name sortKey="Tran, T T" uniqKey="Tran T">T. T. Tran</name></author><author><name sortKey="Alzoubi, K H" uniqKey="Alzoubi K">K. H. Alzoubi</name></author><author><name sortKey="Alkadhi, K A" uniqKey="Alkadhi K">K. A. Alkadhi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fredholm, B B" uniqKey="Fredholm B">B. B. Fredholm</name></author><author><name sortKey="Irenius, E" uniqKey="Irenius E">E. Irenius</name></author><author><name sortKey="Kull, B" uniqKey="Kull B">B. Kull</name></author><author><name sortKey="Schulte, G" uniqKey="Schulte G">G. Schulte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snyder, S H" uniqKey="Snyder S">S. H. Snyder</name></author><author><name sortKey="Katims, J J" uniqKey="Katims J">J. J. Katims</name></author><author><name sortKey="Annau, Z" uniqKey="Annau Z">Z. Annau</name></author><author><name sortKey="Bruns, R F" uniqKey="Bruns R">R. F. Bruns</name></author><author><name sortKey="Daly, J W" uniqKey="Daly J">J. W. Daly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Spealman, R D" uniqKey="Spealman R">R. D. Spealman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Z L" uniqKey="Huang Z">Z. L. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lazarus, M" uniqKey="Lazarus M">M. Lazarus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stenberg, D" uniqKey="Stenberg D">D. Stenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bjorness, T E" uniqKey="Bjorness T">T. E. Bjorness</name></author><author><name sortKey="Kelly, C L" uniqKey="Kelly C">C. L. Kelly</name></author><author><name sortKey="Gao, T" uniqKey="Gao T">T. Gao</name></author><author><name sortKey="Poffenberger, V" uniqKey="Poffenberger V">V. Poffenberger</name></author><author><name sortKey="Greene, R W" uniqKey="Greene R">R. W. Greene</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mustard, J A" uniqKey="Mustard J">J. A. Mustard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dolezelova, E" uniqKey="Dolezelova E">E. Dolezelova</name></author><author><name sortKey="Nothacker, H P" uniqKey="Nothacker H">H. P. Nothacker</name></author><author><name sortKey="Civelli, O" uniqKey="Civelli O">O. Civelli</name></author><author><name sortKey="Bryant, P J" uniqKey="Bryant P">P. J. Bryant</name></author><author><name sortKey="Zurovec, M" uniqKey="Zurovec M">M. Zurovec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, M N" uniqKey="Wu M">M. N. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andretic, R" uniqKey="Andretic R">R. Andretic</name></author><author><name sortKey="Kim, Y C" uniqKey="Kim Y">Y. C. Kim</name></author><author><name sortKey="Jones, F S" uniqKey="Jones F">F. S. Jones</name></author><author><name sortKey="Han, K A" uniqKey="Han K">K. A. Han</name></author><author><name sortKey="Greenspan, R J" uniqKey="Greenspan R">R. J. Greenspan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salmi, P" uniqKey="Salmi P">P. Salmi</name></author><author><name sortKey="Chergui, K" uniqKey="Chergui K">K. Chergui</name></author><author><name sortKey="Fredholm, B B" uniqKey="Fredholm B">B. B. Fredholm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ryder, E" uniqKey="Ryder E">E. Ryder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riemensperger, T" uniqKey="Riemensperger T">T. Riemensperger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gilestro, G F" uniqKey="Gilestro G">G. F. Gilestro</name></author><author><name sortKey="Cirelli, C" uniqKey="Cirelli C">C. Cirelli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pfeiffenberger, C" uniqKey="Pfeiffenberger C">C. Pfeiffenberger</name></author><author><name sortKey="Lear, B C" uniqKey="Lear B">B. C. Lear</name></author><author><name sortKey="Keegan, K P" uniqKey="Keegan K">K. P. Keegan</name></author><author><name sortKey="Allada, R" uniqKey="Allada R">R. Allada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masuyama, K" uniqKey="Masuyama K">K. Masuyama</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Rao, Y" uniqKey="Rao Y">Y. Rao</name></author><author><name sortKey="Wang, J W" uniqKey="Wang J">J. W. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abramoff, M D" uniqKey="Abramoff M">M. D. Abramoff</name></author><author><name sortKey="Magalhaes, P J" uniqKey="Magalhaes P">P. J. Magalhaes</name></author><author><name sortKey="Ram, S J" uniqKey="Ram S">S. J. Ram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, J F" uniqKey="Chen J">J. F. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, X" uniqKey="Xie X">X. Xie</name></author><author><name sortKey="Ramkumar, V" uniqKey="Ramkumar V">V. Ramkumar</name></author><author><name sortKey="Toth, L A" uniqKey="Toth L">L. A. Toth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jurgens, G" uniqKey="Jurgens G">G. Jürgens</name></author><author><name sortKey="Wieschaus, E" uniqKey="Wieschaus E">E. Wieschaus</name></author><author><name sortKey="Nusslein Volhard, C" uniqKey="Nusslein Volhard C">C. Nusslein-Volhard</name></author><author><name sortKey="Kluding, H" uniqKey="Kluding H">H. Kluding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neckameyer, W S" uniqKey="Neckameyer W">W. S. Neckameyer</name></author><author><name sortKey="White, K" uniqKey="White K">K. White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Friggi Grelin, F" uniqKey="Friggi Grelin F">F. Friggi-Grelin</name></author><author><name sortKey="Iche, M" uniqKey="Iche M">M. Iché</name></author><author><name sortKey="Birman, S" uniqKey="Birman S">S. Birman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirsh, J" uniqKey="Hirsh J">J. Hirsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oike, H" uniqKey="Oike H">H. Oike</name></author><author><name sortKey="Kobori, M" uniqKey="Kobori M">M. Kobori</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T. Suzuki</name></author><author><name sortKey="Ishida, N" uniqKey="Ishida N">N. Ishida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Budnik, V" uniqKey="Budnik V">V. Budnik</name></author><author><name sortKey="White, K" uniqKey="White K">K. White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Livingstone, M S" uniqKey="Livingstone M">M. S. Livingstone</name></author><author><name sortKey="Tempel, B L" uniqKey="Tempel B">B. L. Tempel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nall, A H" uniqKey="Nall A">A. H. Nall</name></author><author><name sortKey="Sehgal, A" uniqKey="Sehgal A">A. Sehgal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="N Ssel, D R" uniqKey="N Ssel D">D. R. Nässel</name></author><author><name sortKey="Elekes, K" uniqKey="Elekes K">K. Elekes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Friggi Grelin, F" uniqKey="Friggi Grelin F">F. Friggi-Grelin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mao, Z" uniqKey="Mao Z">Z. Mao</name></author><author><name sortKey="Davis, R L" uniqKey="Davis R">R. L. Davis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kitamoto, T" uniqKey="Kitamoto T">T. Kitamoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author><author><name sortKey="Kodama, L" uniqKey="Kodama L">L. Kodama</name></author><author><name sortKey="Driscoll, M R" uniqKey="Driscoll M">M. R. Driscoll</name></author><author><name sortKey="Wu, M N" uniqKey="Wu M">M. N. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gohl, D M" uniqKey="Gohl D">D. M. Gohl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burke, C J" uniqKey="Burke C">C. J. Burke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ueno, T" uniqKey="Ueno T">T. Ueno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pulver, S R" uniqKey="Pulver S">S. R. Pulver</name></author><author><name sortKey="Pashkovski, S L" uniqKey="Pashkovski S">S. L. Pashkovski</name></author><author><name sortKey="Hornstein, N J" uniqKey="Hornstein N">N. J. Hornstein</name></author><author><name sortKey="Garrity, P A" uniqKey="Garrity P">P. A. Garrity</name></author><author><name sortKey="Griffith, L C" uniqKey="Griffith L">L. C. Griffith</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roehrs, T" uniqKey="Roehrs T">T. Roehrs</name></author><author><name sortKey="Roth, T" uniqKey="Roth T">T. Roth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fredholm, B B" uniqKey="Fredholm B">B. B. Fredholm</name></author><author><name sortKey="Lindstrom, K" uniqKey="Lindstrom K">K. Lindström</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferre, S" uniqKey="Ferre S">S. Ferré</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Finn, I B" uniqKey="Finn I">I. B. Finn</name></author><author><name sortKey="Holtzman, S G" uniqKey="Holtzman S">S. G. Holtzman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobson, K A" uniqKey="Jacobson K">K. A. Jacobson</name></author><author><name sortKey="Von Lubitz, D K" uniqKey="Von Lubitz D">D. K. von Lubitz</name></author><author><name sortKey="Daly, J W" uniqKey="Daly J">J. W. Daly</name></author><author><name sortKey="Fredholm, B B" uniqKey="Fredholm B">B. B. Fredholm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feldman, J F" uniqKey="Feldman J">J. F. Feldman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ganguly Fitzgerald, I" uniqKey="Ganguly Fitzgerald I">I. Ganguly-Fitzgerald</name></author><author><name sortKey="Donlea, J" uniqKey="Donlea J">J. Donlea</name></author><author><name sortKey="Shaw, P J" uniqKey="Shaw P">P. J. Shaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kume, K" uniqKey="Kume K">K. Kume</name></author><author><name sortKey="Kume, S" uniqKey="Kume S">S. Kume</name></author><author><name sortKey="Park, S K" uniqKey="Park S">S. K. Park</name></author><author><name sortKey="Hirsh, J" uniqKey="Hirsh J">J. Hirsh</name></author><author><name sortKey="Jackson, F R" uniqKey="Jackson F">F. R. Jackson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simon, A F" uniqKey="Simon A">A. F. Simon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Solinas, M" uniqKey="Solinas M">M. Solinas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okada, M" uniqKey="Okada M">M. Okada</name></author><author><name sortKey="Mizuno, K" uniqKey="Mizuno K">K. Mizuno</name></author><author><name sortKey="Kaneko, S" uniqKey="Kaneko S">S. Kaneko</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wisor, J P" uniqKey="Wisor J">J. P. Wisor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holst, S C" uniqKey="Holst S">S. C. Holst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Claridge Chang, A" uniqKey="Claridge Chang A">A. Claridge-Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riemensperger, T" uniqKey="Riemensperger T">T. Riemensperger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pech, U" uniqKey="Pech U">U. Pech</name></author><author><name sortKey="Pooryasin, A" uniqKey="Pooryasin A">A. Pooryasin</name></author><author><name sortKey="Birman, S" uniqKey="Birman S">S. Birman</name></author><author><name sortKey="Fiala, A" uniqKey="Fiala A">A. Fiala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, S" uniqKey="Lin S">S. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agrawal, T" uniqKey="Agrawal T">T. Agrawal</name></author><author><name sortKey="Hasan, G" uniqKey="Hasan G">G. Hasan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ribeiro, J A" uniqKey="Ribeiro J">J. A. Ribeiro</name></author><author><name sortKey="Sebastiao, A M" uniqKey="Sebastiao A">A. M. Sebastião</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcpherson, P S" uniqKey="Mcpherson P">P. S. McPherson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26868675</article-id><article-id pub-id-type="pmc">4751479</article-id><article-id pub-id-type="pii">srep20938</article-id><article-id pub-id-type="doi">10.1038/srep20938</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Caffeine promotes wakefulness via dopamine signaling in <italic>Drosophila</italic></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Nall</surname><given-names>Aleksandra H.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Shakhmantsir</surname><given-names>Iryna</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cichewicz</surname><given-names>Karol</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Birman</surname><given-names>Serge</given-names></name><xref ref-type="aff" rid="a2">2</xref></contrib><contrib contrib-type="author"><name><surname>Hirsh</surname><given-names>Jay</given-names></name><xref ref-type="aff" rid="a3">3</xref></contrib><contrib contrib-type="author"><name><surname>Sehgal</surname><given-names>Amita</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref><xref ref-type="aff" rid="a4">4</xref></contrib><aff id="a1"><label>1</label><institution>Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></aff><aff id="a2"><label>2</label><institution>Genes Circuits Rhythms and Neuropathologies, Brain Plasticity Unit, CNRS, PSL Research University</institution>, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris,<country>France</country></aff><aff id="a3"><label>3</label><institution>Department of Biology, University of Virginia</institution>, Charlottesville, VA 22904,<country>USA</country></aff><aff id="a4"><label>4</label><institution>Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania</institution>, Philadelphia, PA 19104,<country>USA</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>amita@mail.med.upenn.edu</email></corresp></author-notes><pub-date pub-type="epub"><day>12</day><month>02</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>6</volume><elocation-id>20938</elocation-id><history><date date-type="received"><day>11</day><month>10</month><year>2015</year></date><date date-type="accepted"><day>10</day><month>12</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2016, Macmillan Publishers Limited</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Macmillan Publishers Limited</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly <italic>Drosophila melanogaster</italic>, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>The response to caffeine in <italic>Drosophila</italic> requires dopamine synthesis.</title><p>Sleep profiles and quantified nighttime sleep for female (<bold>A</bold>) iso31, (<bold>B</bold>) <italic>DTH BAC</italic>, and (<bold>C</bold>) <italic>DTH</italic><sup><italic>FS</italic>±</sup><italic>BAC</italic> flies. Actograms depict minutes of sleep per 30 minute sliding window across a 24-hour period composed of 12 hours of light (white bar) and 12 hours of dark (black bar). Sleep is shown for flies on drug-free food (black line) or food containing 0.5 mg/ml caffeine (blue line). Bar graphs quantify average number of minutes of sleep per night for flies of each genotype fed either drug-free food or food containing 0.2, 0.5, or 1 mg/ml caffeine. (<bold>D</bold>) The average minutes of nighttime sleep is shown for female iso31 flies fed either drug-free food (white bars) or food containing 0.5 mg/ml caffeine (black bars) during each of the 5 nights of activity monitoring. (<bold>E</bold>) Circadian period of free-running rest-activity rhythms is plotted for the same three genotypes fed drug-free food or food containing 0.5 mg/ml caffeine. Error bars show standard deviation. See text for details of the statistical analysis. Statistical significance thresholds are as follows: * for p < .05, ** for p < .01, *** for p < .001, **** for p < .0001.</p></caption><graphic xlink:href="srep20938-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Caffeine requires dopaminergic signaling upstream of DTH.</title><p>Sleep profiles for female (<bold>A</bold>) iso31, (<bold>B</bold>) <italic>DTH BAC</italic>, and (<bold>C</bold>) <italic>DTH</italic><sup><italic>FS</italic>±</sup><italic>BAC</italic> flies. Actograms depict minutes of sleep per 30 minute sliding window across a 24-hour period composed of 12 hours of light (white bar) and 12 hours of dark (black bar). Sleep is shown for flies on food containing 3 mg/ml L-DOPA (black line) or food containing 3 mg/ml L-DOPA and 0.5 mg/ml caffeine (blue line). Bar graphs quantify average number of minutes of nighttime sleep for flies of each genotype fed drug-free food (white bars), food containing 0.5 mg/ml caffeine (small check bars), food containing 3 mg/ml L-DOPA (large check bars), or food containing 3 mg/ml L-DOPA and 0.5 mg/ml caffeine (black bars). Error bars show standard deviation. See text for details of the statistical analysis.</p></caption><graphic xlink:href="srep20938-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><title>The response to caffeine requires synaptic packaging of dopamine.</title><p>Sleep profiles for female (<bold>A</bold>) iso31 and (<bold>B</bold>) DVMAT<sup>p1</sup> flies assayed on drug-free food (black line) or food containing 0.5 mg/ml caffeine (blue line). Graphs depict minutes of sleep per 30 minute sliding window across a 24-hour period composed of 12 hours of light (white bar) and 12 hours of dark (black bar). (<bold>C</bold>) Average number of minutes of nighttime sleep for flies fed drug-free food (white bars) or food containing 0.5 mg/ml caffeine (black bars). Error bars show standard deviation.</p></caption><graphic xlink:href="srep20938-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><title>Mapping dopaminergic neurons required for the caffeine response.</title><p>Average number of minutes of nighttime sleep for (<bold>A</bold>) male and (<bold>B</bold>) female flies containing various restricted dopaminergic Gal4 constructs driving expression of temperature-sensitive Shibire (UAS-Shi<sup>ts</sup>). Control flies contain the UAS-Shi<sup>ts</sup> transgene in the absence of a Gal4 driver. Nighttime sleep is averaged across three nights at the 30 °C restrictive temperature on drug-free food (white bars) or food containing 0.5 mg/ml caffeine (black bars). Error bars show standard deviation.</p></caption><graphic xlink:href="srep20938-f4"></graphic></fig><fig id="f5"><label>Figure 5</label><caption><title>Caffeine causes increased activity of PAM cluster neurons.</title><p>Immunostaining of the CaLexA signal (GFP, green) and neuropil (nc82, magenta) in brains of flies expressing the CaLexA construct under the control of the 0273-Gal4 driver to visualize PAM cluster neurons or the broader TH-Gal4 driver to visualize PPM3 cluster neurons. Flies were fed either (<bold>A,E</bold>) drug-free food or (<bold>B,F</bold>) food containing 0.5 mg/ml caffeine for 24 hours prior to dissection and staining. The GFP intensity was quantified on a cell-by-cell basis in each brain. (<bold>C,G</bold>) The average cell intensity for each brain is plotted for drug-free and caffeine-fed groups. (<bold>D,H</bold>) The number of visible GFP-positive cells in each brain is plotted for drug-free and caffeine-fed groups. Large horizontal line reflects the average, and error bars show standard deviation.</p></caption><graphic xlink:href="srep20938-f5"></graphic></fig><fig id="f6"><label>Figure 6</label><caption><title>PAM cluster neurons promote wake.</title><p>Sleep profiles for female 0273-Gal4 control flies (black), UAS-TrpA1 control flies (blue), or 0273-Gal4 > UAS-TrpA1 experimental flies (green) averaged across three days at (<bold>A</bold>) 21 °C and (<bold>B</bold>) 28 °C. Graphs depict minutes of sleep per 30 minute sliding window across a 24-hour period composed of 12 hours of light (white bar) and 12 hours of dark (black bar). (<bold>C</bold>) Average number of minutes of nighttime sleep for (<bold>C</bold>) male and (<bold>D</bold>) female flies of the three different genotypes assayed at high and low temperatures. Error bars show standard deviation.</p></caption><graphic xlink:href="srep20938-f6"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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