Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


In the fruit fly, Drosophila melanogaster, the daily cycle of rest and activity is a rhythmic behavior that relies on the activity of a small number of neurons. The small ventral lateral neurons (sLNvs) are considered key in the control of locomotor rhythmicity. Previous work from our laboratory has showed that these neurons undergo structural remodeling on their axonal projections on a daily basis. Such remodeling endows sLNvs with the possibility to make synaptic contacts with different partners at different times throughout the day, as has been previously described. By using different genetic tools to alter membrane excitability of the sLNv putative postsynaptic partners, we tested their functional role in the control of locomotor activity. We also used optical imaging to test the functionality of these contacts. We found that these different neuronal groups affect the consolidation of rhythmic activity, suggesting that non-circadian cells are part of the circuit that controls locomotor activity. Our results suggest that new neuronal groups, in addition to the well-characterized clock neurons, contribute to the operations of the circadian network that controls locomotor activity in D. melanogaster. © 2019. Published by The Company of Biologists Ltd.


Documento: Artículo
Título:Contribution of non-circadian neurons to the temporal organization of locomotor activity
Autor:Pırez, N.; Bernabei-Cornejo, S.G.; Fernandez-Acosta, M.; Duhart, J.M.; Fernanda Ceriani, M.
Filiación:Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, Instituto de Investigaciones Bioquımicas –Buenos Aires (IIB–BA, CONICET), Buenos Aires, 1425, Argentina
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiologıá, Biologıá Molecular y Celular and CONICET, Universidad de Buenos Aires, Instituto de Fisiologıá, Biologıá Molecular y Neurociencias (IFIByNE), Buenos Aires, 1428, Argentina
Unidad de Transferencia Genética, Instituto de Oncologıá Ángel H., Roffo, Buenos Aires, 1417, Argentina
Palabras clave:Connectivity; Drosophila; Locomotor rhythms; Non-circadian neurons; SLNvs; article; Drosophila; excitability; fluorescence imaging; locomotion; membrane; nonhuman; rhythm; synapse
Título revista:Biology Open
Título revista abreviado:Biol. Open


  • Beckwith, E.J., Ceriani, M.F., Experimental assessment of the network properties of the Drosophila circadian clock (2015) J. Comp. Neurol., 523, pp. 982-996
  • Beckwith, E.J., Gorostiza, E.A., Berni, J., Rezával, C., Pérez-Santángelo, A., Nadra, A.D., Ceriani, M.F., Circadian period integrates network information through activation of the BMP signaling pathway (2013) PLoS Biol, 11
  • Berni, J., Beckwith, E.J., Fernandez, M.P., Ceriani, M.F., The axon-guidance roundabout gene alters the pace of the Drosophila circadian clock (2008) Eur. J. Neurosci., 27, pp. 396-407
  • Cao, G., Platisa, J., Pieribone, V.A., Raccuglia, D., Kunst, M., Nitabach, M.N., Genetically targeted optical electrophysiology in intact neural circuits (2013) Cell, 154, pp. 904-913
  • Cavanaugh, D.J., Geratowski, J.D., Wooltorton, J.R., Spaethling, J.M., Hector, C.E., Zheng, X., Johnson, E.C., Sehgal, A., Identification of a circadian output circuit for rest:activity rhythms in Drosophila (2014) Cell, 157, pp. 689-701
  • Cavey, M., Collins, B., Bertet, C., Blau, J., Circadian rhythms in neuronal activity propagate through output circuits (2016) Nat. Neurosci., 19, pp. 587-595
  • Chouhan, N.S., Wolf, R., Helfrich-Förster, C., Heisenberg, M., Flies remember the time of day (2015) Curr. Biol., 25, pp. 1619-1624
  • Chung, B.Y., Kilman, V.L., Keath, J.R., Pitman, J.L., Allada, R., The GABA(A) receptor RDL acts in peptidergic PDF neurons to promote sleep in Drosophila (2009) Curr. Biol., 19, pp. 386-390
  • Depetris-Chauvin, A., Berni, J., Aranovich, E.J., Muraro, N.I., Beckwith, E.J., Ceriani, M.F., Adult-specific electrical silencing of pacemaker neurons uncouples molecular clock from circadian outputs (2011) Curr. Biol., 21, pp. 1783-1793
  • Dissel, S., Hansen, C.N., Özkaya, O., Hemsley, M., Kyriacou, C.P., Rosato, E., The logic of circadian organization in Drosophila (2014) Curr. Biol., 24, pp. 2257-2266
  • Dubnau, J., Grady, L., Kitamoto, T., Tully, T., Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory (2001) Nature, 411, pp. 476-480
  • Edelstein, A., Amodaj, N., Hoover, K., Vale, R., Stuurman, N., Computer control of microscopes using microManager. Current protocols in molecular (2010) Current Protocols in Molecular Biology, 92 (1), pp. 14.20.1-14.20.17
  • Emery, P., So, W.V., Kaneko, M., Hall, J.C., Rosbash, M., CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity (1998) Cell, 95, pp. 669-679
  • Feinberg, E.H., Vanhoven, M.K., Bendesky, A., Wang, G., Fetter, R.D., Shen, K., Bargmann, C.I., GFP Reconstitution Across Synaptic Partners (GRASP) defines cell contacts and synapses in living nervous systems (2008) Neuron, 57, pp. 353-363
  • Fernandez, M.P., Berni, J., Ceriani, M.F., Circadian remodeling of neuronal circuits involved in rhythmic behavior (2008) PLoS Biol, 6
  • Frenkel, L., Muraro, N.I., Beltrán González, A.N., Marcora, M.S., Bernabó, G., Hermann-Luibl, C., Romero, J.I., Marino-Busjle, C., Organization of circadian behavior relies on glycinergic transmission (2017) Cell Reports, 19, pp. 72-85
  • Gordon, M.D., Scott, K., Motor control in a Drosophila taste circuit (2009) Neuron, 61, pp. 373-384
  • Gorostiza, E.A., Ceriani, M.F., Retrograde bone morphogenetic protein signaling shapes a key circadian pacemaker circuit (2013) J. Neurosci., 33, pp. 687-696
  • Gorostiza, E.A., Depetris-Chauvin, A., Frenkel, L., Pırez, N., Ceriani, M.F., Circadian pacemaker neurons change synaptic contacts across the day (2014) Curr. Biol., 24, pp. 2161-2167
  • Grima, B., Chelot, E., Xia, R., Rouyer, F., Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain (2004) Nature, 431, pp. 869-873
  • Gummadova, J.O., Coutts, G.A., Glossop, N.R.J., Analysis of the Drosophila Clock promoter reveals heterogeneity in expression between subgroups of central oscillator cells and identifies a novel enhancer region (2009) J. Biol. Rhythms, 24, pp. 353-367
  • Guo, F., Yu, J., Jung, H.J., Abruzzi, K.C., Luo, W., Griffith, L.C., Rosbash, M., Circadian neuron feedback controls the Drosophila sleep-activity profile (2016) Nature, 536, pp. 292-297
  • Helfrich-Förster, C., The neuroarchitecture of the circadian clock in the brain of Drosophila melanogaster (2003) Microsc. Res. Tech., 62, pp. 94-102
  • Helfrich-Förster, C., Wulf, J., De Belle, J.S., Mushroom body influence on locomotor activity and circadian rhythms in Drosophila melanogaster (2002) J. Neurogenet., 16, pp. 73-109
  • Herrero, A., Duhart, J.M., Ceriani, M.F., Neuronal and glial clocks underlying structural remodeling of pacemaker neurons in drosophila (2017) Front. Physiol., 8, p. 918
  • Hu, A., Zhang, W., Wang, Z., Functional feedback from mushroom bodies to antennal lobes in the Drosophila olfactory pathway (2010) Proc. Natl Acad. Sci. USA, 107, pp. 10262-10267
  • Hyun, S., Lee, Y., Hong, S.-T., Bang, S., Paik, D., Kang, J., Shin, J., Hwang, S., Drosophila GPCR Han is a receptor for the circadian clock neuropeptide PDF (2005) Neuron, 48, pp. 267-278
  • Im, S.H., Taghert, P.H., PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila (2010) J. Comp. Neurol., 518, pp. 1925-1945
  • Kaneko, M., Hall, J.C., Neuroanatomy of cells expressing clock genes in Drosophila: Transgenic manipulation of the period and timeless genes to mark the perikarya of circadian pacemaker neurons and their projections (2000) J. Comp. Neurol., 422, pp. 66-94
  • Keene, A.C., Waddell, S., Drosophila olfactory memory: Single genes to complex neural circuits (2007) Nat. Rev. Neurosci., 8, pp. 341-354
  • King, A.N., Barber, A.F., Smith, A.E., Dreyer, A.P., Sitaraman, D., Nitabach, M.N., Cavanaugh, D.J., Sehgal, A., A peptidergic circuit links the circadian clock to locomotor activity (2017) Curr. Biol., 27, pp. 1915-1927
  • Lear, B.C., Zhang, L., Allada, R., The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior (2009) PLoS Biol, 7
  • Lima, S.Q., Miesenböck, G., Remote control of behavior through genetically targeted photostimulation of neurons (2005) Cell, 121, pp. 141-152
  • Liu, S., Lamaze, A., Liu, Q., Tabuchi, M., Yang, Y., Fowler, M., Bharadwaj, R., Blackshaw, S., WIDE AWAKE mediates the circadian timing of sleep onset (2014) Neuron, 82, pp. 151-166
  • Lyons, L.C., Roman, G., Circadian modulation of short-term memory in Drosophila (2009) Learn. Mem., 16, pp. 19-27
  • Mabuchi, I., Shimada, N., Sato, S., Ienaga, K., Inami, S., Sakai, T., Mushroom body signaling is required for locomotor activity rhythms in Drosophila (2016) Neurosci. Res., 111, pp. 25-33
  • Nitabach, M.N., Blau, J., Holmes, T.C., Electrical silencing of Drosophila pacemaker neurons stops the free-running circadian clock (2002) Cell, 109, pp. 485-495
  • Parisky, K.M., Agosto, J., Pulver, S.R., Shang, Y., Kuklin, E., Hodge, J.J.L., Kang, K., Rosbash, M., PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit (2008) Neuron, 60, pp. 672-682
  • Pırez, N., Christmann, B.L., Griffith, L.C., Daily rhythms in locomotor circuits in Drosophila involve pigment-dispersing factor (PDF) (2013) J. Neurophysiol., 110, pp. 700-708
  • Pitman, J.L., McGill, J.J., Keegan, K.P., Allada, R., A dynamic role for the mushroom bodies in promoting sleep in Drosophila (2006) Nature, 441, pp. 753-756
  • Renn, S.C., Park, J.H., Rosbash, M., Hall, J.C., Taghert, P.H., A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila (1999) Cell, 99, pp. 791-802
  • Rosenzweig, M., Kang, K., Garrity, P.A., Distinct TRP channels are required for warm and cool avoidance in Drosophila melanogaster (2008) Proc. Natl. Acad. Sci. USA, 105, pp. 14668-14673
  • Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Schmid, B., Fiji: An open-source platform for biological-image analysis (2012) Nat. Methods, 9, pp. 676-682
  • Schlichting, M., Menegazzi, P., Lelito, K.R., Yao, Z., Buhl, E., Dalla Benetta, E., Bahle, A., Helfrich-Forster, C., A neural network underlying circadian entrainment and photoperiodic adjustment of sleep and activity in drosophila (2016) J. Neurosci., 36, pp. 9084-9096
  • Shafer, O.T., Helfrich-Förster, C., Renn, S.C.P., Taghert, P.H., Reevaluation of Drosophila melanogaster’s neuronal circadian pacemakers reveals new neuronal classes (2006) J. Comp. Neurol., 498, pp. 180-193
  • Shafer, O.T., Kim, D.J., Dunbar-Yaffe, R., Nikolaev, V.O., Lohse, M.J., Taghert, P.H., Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging (2008) Neuron, 58, pp. 223-237
  • Shang, Y., Griffith, L.C., Rosbash, M., Light-arousal and circadian photoreception circuits intersect at the large PDF cells of the Drosophila brain (2008) Proc. Natl. Acad. Sci. USA, 105, pp. 19587-19594
  • Shang, Y., Haynes, P., Pırez, N., Harrington, K.I., Guo, F., Pollack, J., Hong, P., Rosbash, M., Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine (2011) Nat. Neurosci., 14, pp. 889-895
  • Shaw, P.J., Cirelli, C., Greenspan, R.J., Tononi, G., Correlates of sleep and waking in Drosophila melanogaster (2000) Science, 287, pp. 1834-1837
  • Shearin, H.K., Quinn, C.D., Mackin, R.D., Macdonald, I.S., Stowers, R.S., T-GRASP, a targeted GRASP for assessing neuronal connectivity (2018) J. Neurosci. Methods, 306, pp. 94-102
  • Sheeba, V., Fogle, K.J., Kaneko, M., Rashid, S., Chou, Y.-T., Sharma, V.K., Holmes, T.C., Large ventral lateral neurons modulate arousal and sleep in Drosophila (2008) Curr. Biol., 18, pp. 1537-1545
  • Stoleru, D., Peng, Y., Agosto, J., Rosbash, M., Coupled oscillators control morning and evening locomotor behaviour of Drosophila (2004) Nature, 431, pp. 862-868
  • Stoleru, D., Peng, Y., Nawathean, P., Rosbash, M., A resetting signal between Drosophila pacemakers synchronizes morning and evening activity (2005) Nature, 438, pp. 238-242
  • Talay, M., Richman, E.B., Snell, N.J., Hartmann, G.G., Fisher, J.D., Sorkac, A., Santoyo, J.F., Johnson, M., Transsynaptic mapping of second-order taste neurons in flies by trans-tango (2017) Neuron, 96, pp. 783-795. , e784
  • Tang, X., Roessingh, S., Hayley, S.E., Chu, M.L., Tanaka, N.K., Wolfgang, W., Song, S., Hamada, F.N., The role of PDF neurons in setting the preferred temperature before dawn in Drosophila (2017) eLife, 6, p. e23206
  • Tian, L., Hires, S.A., Mao, T., Huber, D., Chiappe, M.E., Chalasani, S.H., Petreanu, L., Schreiter, E.R., Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators (2009) Nat. Methods, 6, pp. 875-881
  • Wang, J.W., Wong, A.M., Flores, J., Vosshall, L.B., Axel, R., Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain (2003) Cell, 112, pp. 271-282
  • Wülbeck, C., Grieshaber, E., Helfrich-Förster, C., Blocking endocytosis in Drosophila’s circadian pacemaker neurons interferes with the endogenous clock in a PDF-dependent way (2009) Chronobiol. Int., 26, pp. 1307-1322
  • Yang, H.H., St-Pierre, F., Sun, X., Ding, X., Lin, M.Z., Clandinin, T.R., Subcellular imaging of voltage and calcium signals reveals neural processing in vivo (2016) Cell, 166, pp. 245-257
  • Yao, Z., Shafer, O.T., The Drosophila circadian clock is a variably coupled network of multiple peptidergic units (2014) Science, 343, pp. 1516-1520
  • Yao, Z., Macara, A.M., Lelito, K.R., Minosyan, T.Y., Shafer, O.T., Analysis of functional neuronal connectivity in the Drosophila brain (2012) J. Neurophysiol., 108, pp. 684-696
  • Yi, W., Zhang, Y., Tian, Y., Guo, J., Li, Y., Guo, A., A subset of cholinergic mushroom body neurons requires Go signaling to regulate sleep in Drosophila (2013) Sleep, 36, pp. 1809-1821
  • Yoshii, T., Wulbeck, C., Sehadova, H., Veleri, S., Bichler, D., Stanewsky, R., Helfrich-Forster, C., The neuropeptide pigment-dispersing factor adjusts period and phase of Drosophila’s clock (2009) J. Neurosci., 29, pp. 2597-2610
  • Zhang, L., Chung, B.Y., Lear, B.C., Kilman, V.L., Liu, Y., Mahesh, G., Meissner, R.-A., Allada, R., DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila (2010) Curr. Biol., 20, pp. 591-599


---------- APA ----------
Pırez, N., Bernabei-Cornejo, S.G., Fernandez-Acosta, M., Duhart, J.M. & Fernanda Ceriani, M. (2019) . Contribution of non-circadian neurons to the temporal organization of locomotor activity. Biology Open, 8(1).
---------- CHICAGO ----------
Pırez, N., Bernabei-Cornejo, S.G., Fernandez-Acosta, M., Duhart, J.M., Fernanda Ceriani, M. "Contribution of non-circadian neurons to the temporal organization of locomotor activity" . Biology Open 8, no. 1 (2019).
---------- MLA ----------
Pırez, N., Bernabei-Cornejo, S.G., Fernandez-Acosta, M., Duhart, J.M., Fernanda Ceriani, M. "Contribution of non-circadian neurons to the temporal organization of locomotor activity" . Biology Open, vol. 8, no. 1, 2019.
---------- VANCOUVER ----------
Pırez, N., Bernabei-Cornejo, S.G., Fernandez-Acosta, M., Duhart, J.M., Fernanda Ceriani, M. Contribution of non-circadian neurons to the temporal organization of locomotor activity. Biol. Open. 2019;8(1).