The Drosophila Circadian Clock Is a Variably Coupled Network of Multiple Peptidergic Units

Circadian Rhythms Circadian rhythms in the fruit fly Drosophila are driven by neurons in the brain. Yao and Shafer (p. 1516) analyzed different sets of neurons that can drive circadian rhythms. Manipulating the period of each set of neurons separately revealed that when the various clock signals were fairly consistent, the fly showed a robust circadian rhythm. But when the various clock signals were seriously out of sync with one another, the fly was oblivious to the day-night cycle. Behavioral rhythms emerge from the interactions of many independent oscillators rather than from a group of master pacemakers. Daily rhythms in behavior emerge from networks of neurons that express molecular clocks. Drosophila’s clock neuron network consists of a diversity of cell types, yet is modeled as two hierarchically organized groups, one of which serves as a master pacemaker. Here, we establish that the fly’s clock neuron network consists of multiple units of independent neuronal oscillators, each unified by its neuropeptide transmitter and mode of coupling to other units. Our work reveals that the circadian clock neuron network is not orchestrated by a small group of master pacemakers but rather consists of multiple independent oscillators, each of which drives rhythms in activity.

[1]  J. C. Hall,et al.  Spatial and temporal expression of the period gene in Drosophila melanogaster. , 1988, Genes & development.

[2]  Kevin P. Keegan,et al.  Locomotor activity level monitoring using the Drosophila Activity Monitoring (DAM) System. , 2010, Cold Spring Harbor protocols.

[3]  C. Helfrich-Förster,et al.  Reevaluation of Drosophila melanogaster's neuronal circadian pacemakers reveals new neuronal classes , 2006, The Journal of comparative neurology.

[4]  C. Helfrich-Förster,et al.  Peptidergic clock neurons in Drosophila: Ion transport peptide and short neuropeptide F in subsets of dorsal and ventral lateral neurons , 2009, The Journal of comparative neurology.

[5]  N. J. De Souza,et al.  Forskolin: A labdane diterpenoid with antihypertensive, positive inotropic, platelet aggregation inhibitory, and adenylate cyclase activating properties , 1983, Medicinal research reviews.

[6]  G. Korge,et al.  Innervation of the ring gland of Drosophila melanogaster , 2001, The Journal of comparative neurology.

[7]  R J Konopka,et al.  Clock mutants of Drosophila melanogaster. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. Ueda,et al.  Light Activates Output from Evening Neurons and Inhibits Output from Morning Neurons in the Drosophila Circadian Clock , 2007, PLoS biology.

[9]  Y. Jan,et al.  Properties of the larval neuromuscular junction in Drosophila melanogaster. , 1976, The Journal of physiology.

[10]  P. Taghert,et al.  PDFR and CRY Signaling Converge in a Subset of Clock Neurons to Modulate the Amplitude and Phase of Circadian Behavior in Drosophila , 2011, PloS one.

[11]  Kevin P. Keegan,et al.  Processing circadian data collected from the Drosophila Activity Monitoring (DAM) System. , 2010, Cold Spring Harbor protocols.

[12]  Pierre Trifilieff,et al.  Intrinsic neurons of Drosophila mushroom bodies express short neuropeptide F: Relations to extrinsic neurons expressing different neurotransmitters , 2008, The Journal of comparative neurology.

[13]  José Agosto,et al.  Coupled oscillators control morning and evening locomotor behaviour of Drosophila , 2004, Nature.

[14]  J. Truman,et al.  Sequential Nuclear Accumulation of the Clock Proteins Period and Timeless in the Pacemaker Neurons of Drosophila melanogaster , 2002, The Journal of Neuroscience.

[15]  M. W. Young,et al.  A Role for the Segment Polarity Gene shaggy/GSK-3 in the Drosophila Circadian Clock , 2001, Cell.

[16]  Dan Stoleru,et al.  A resetting signal between Drosophila pacemakers synchronizes morning and evening activity , 2005, Nature.

[17]  T. Préat,et al.  Defining the role of Drosophila lateral neurons in the control of circadian rhythms in motor activity and eclosion by targeted genetic ablation and PERIOD protein overexpression , 2001, The European journal of neuroscience.

[18]  Martin J. Lohse,et al.  Novel Single Chain cAMP Sensors for Receptor-induced Signal Propagation*♦ , 2004, Journal of Biological Chemistry.

[19]  P. Hardin,et al.  Circadian oscillators of Drosophila and mammals , 2006, Journal of Cell Science.

[20]  J. Price,et al.  Drosophila DBT Lacking Protein Kinase Activity Produces Long-Period and Arrhythmic Circadian Behavioral and Molecular Rhythms , 2007, Molecular and Cellular Biology.

[21]  François Rouyer,et al.  Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain , 2004, Nature.

[22]  M. Bourouis Targeted increase in shaggy activity levels blocks wingless signaling , 2002, Genesis.

[23]  P. Sokolove,et al.  The chi square periodogram: its utility for analysis of circadian rhythms. , 1978, Journal of theoretical biology.

[24]  J. Ashby References and Notes , 1999 .

[25]  Erik D. Herzog,et al.  Neurons and networks in daily rhythms , 2007, Nature Reviews Neuroscience.

[26]  M. Vansteensel,et al.  Organization of cell and tissue circadian pacemakers: A comparison among species , 2008, Brain Research Reviews.

[27]  O. Shafer,et al.  Analysis of functional neuronal connectivity in the Drosophila brain. , 2012, Journal of neurophysiology.

[28]  Francis J. Doyle,et al.  Intercellular Coupling Confers Robustness against Mutations in the SCN Circadian Clock Network , 2007, Cell.

[29]  E. Bae,et al.  Drosophila GPCR Han Is a Receptor for the Circadian Clock Neuropeptide PDF , 2005, Neuron.

[30]  P. Taghert,et al.  PDF receptor expression reveals direct interactions between circadian oscillators in drosophila , 2010, The Journal of comparative neurology.

[31]  T. Todo,et al.  Cryptochrome is present in the compound eyes and a subset of Drosophila's clock neurons , 2008, The Journal of comparative neurology.

[32]  S. Yamaguchi,et al.  Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus , 2003, Science.

[33]  Dan Stoleru,et al.  The Drosophila Circadian Network Is a Seasonal Timer , 2007, Cell.

[34]  V. Kilman,et al.  DN1p Circadian Neurons Coordinate Acute Light and PDF Inputs to Produce Robust Daily Behavior in Drosophila , 2010, Current Biology.

[35]  N. Glossop,et al.  Analysis of the Drosophila Clock Promoter Reveals Heterogeneity in Expression between Subgroups of Central Oscillator Cells and Identifies a Novel Enhancer Region , 2009, Journal of biological rhythms.

[36]  P. Taghert,et al.  Widespread Receptivity to Neuropeptide PDF throughout the Neuronal Circadian Clock Network of Drosophila Revealed by Real-Time Cyclic AMP Imaging , 2008, Neuron.