Control of Sleep by Dopaminergic Inputs to the Drosophila Mushroom Body

The Drosophila mushroom body (MB) is an associative learning network that is important for the control of sleep. We have recently identified particular intrinsic MB Kenyon cell (KC) classes that regulate sleep through synaptic activation of particular MB output neurons (MBONs) whose axons convey sleep control signals out of the MB to downstream target regions. Specifically, we found that sleep-promoting KCs increase sleep by preferentially activating cholinergic sleep-promoting MBONs, while wake-promoting KCs decrease sleep by preferentially activating glutamatergic wake-promoting MBONs. Here we use a combination of genetic and physiological approaches to identify wake-promoting dopaminergic neurons (DANs) that innervate the MB, and show that they activate wake-promoting MBONs. These studies reveal a dopaminergic sleep control mechanism that likely operates by modulation of KC-MBON microcircuits.

[1]  Matthew S. Thimgan,et al.  Inducing Sleep by Remote Control Facilitates Memory Consolidation in Drosophila , 2011, Science.

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

[3]  Gerald M. Rubin,et al.  A Higher Brain Circuit for Immediate Integration of Conflicting Sensory Information in Drosophila , 2015, Current Biology.

[4]  G. Rubin,et al.  Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila , 2014, eLife.

[5]  S. Tomchik,et al.  Dopaminergic Modulation of cAMP Drives Nonlinear Plasticity across the Drosophila Mushroom Body Lobes , 2014, Current Biology.

[6]  G. Rubin,et al.  Tools for neuroanatomy and neurogenetics in Drosophila , 2008, Proceedings of the National Academy of Sciences.

[7]  G. Rubin,et al.  A subset of dopamine neurons signals reward for odour memory in Drosophila , 2012, Nature.

[8]  Julie H. Simpson,et al.  A GAL4-driver line resource for Drosophila neurobiology. , 2012, Cell reports.

[9]  A Borst,et al.  Drosophila mushroom body mutants are deficient in olfactory learning. , 1985, Journal of neurogenetics.

[10]  R. Strauss,et al.  A higher control center of locomotor behavior in the Drosophila brain , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  Benjamin H. White,et al.  Sleep in Drosophila is regulated by adult mushroom bodies , 2006, Nature.

[12]  Allan I Pack,et al.  Rest in Drosophila Is a Sleep-like State , 2000, Neuron.

[13]  Kei Ito,et al.  Neuronal assemblies of the Drosophila mushroom body , 2008, The Journal of comparative neurology.

[14]  A. Aertsen,et al.  Neuronal assemblies , 1989, IEEE Transactions on Biomedical Engineering.

[15]  A. Guo,et al.  A subset of cholinergic mushroom body neurons requires Go signaling to regulate sleep in Drosophila. , 2013, Sleep.

[16]  D. Nässel,et al.  Aminergic neurons in the brain of blowflies and Drosophila: dopamine- and tyrosine hydroxylase-immunoreactive neurons and their relationship with putative histaminergic neurons , 2004, Cell and Tissue Research.

[17]  S. Duntley,et al.  Notch Signaling Modulates Sleep Homeostasis and Learning after Sleep Deprivation in Drosophila , 2011, Current Biology.

[18]  Stefan R. Pulver,et al.  An internal thermal sensor controlling temperature preference in Drosophila , 2008, Nature.

[19]  A. Guo,et al.  Go signaling in mushroom bodies regulates sleep in Drosophila. , 2011, Sleep.

[20]  V. Budnik,et al.  Catecholamine‐containing neurons in Drosophila melanogaster: Distribution and development , 1988, The Journal of comparative neurology.

[21]  Yoshinori Aso,et al.  Distinct dopamine neurons mediate reward signals for short- and long-term memories , 2014, Proceedings of the National Academy of Sciences.

[22]  Sang Ki Park,et al.  Dopamine Is a Regulator of Arousal in the Fruit Fly , 2005, The Journal of Neuroscience.

[23]  T. Scammell,et al.  Sleep neurobiology from a clinical perspective. , 2011, Sleep.

[24]  Kevin P. Keegan,et al.  A dynamic role for the mushroom bodies in promoting sleep in Drosophila , 2006, Nature.

[25]  J. Pollack,et al.  Imaging analysis of clock neurons: light buffers the wake-promoting effect of dopamine , 2011, Nature Neuroscience.

[26]  Qili Liu,et al.  Two Dopaminergic Neurons Signal to the Dorsal Fan-Shaped Body to Promote Wakefulness in Drosophila , 2012, Current Biology.

[27]  G. Rubin,et al.  The neuronal architecture of the mushroom body provides a logic for associative learning , 2014, eLife.

[28]  K. Kume,et al.  Functional characterization of dopamine transporter in vivo using Drosophila melanogaster behavioral assays , 2014, Front. Behav. Neurosci..

[29]  A. Grosmark,et al.  Dopaminergic Control of Sleep–Wake States , 2006, The Journal of Neuroscience.

[30]  James W. Truman,et al.  Transvection Is Common Throughout the Drosophila Genome , 2012, Genetics.

[31]  M Heisenberg,et al.  Localization of a short-term memory in Drosophila. , 2000, Science.

[32]  J. Sharma,et al.  SLEEP DISORDERS IN PARKINSON'S DISEASE , 2003, International journal of clinical practice.

[33]  Leslie C Griffith,et al.  A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster , 2015, eLife.

[34]  Quan Yuan,et al.  A Sleep-Promoting Role for the Drosophila Serotonin Receptor 1A , 2006, Current Biology.

[35]  Raju Tomer,et al.  Profiling by Image Registration Reveals Common Origin of Annelid Mushroom Bodies and Vertebrate Pallium , 2010, Cell.

[36]  W. Joiner,et al.  SLEEPLESS Is a Bifunctional Regulator of Excitability and Cholinergic Synaptic Transmission , 2014, Current Biology.

[37]  H. Landolt,et al.  Catechol-O-methyltransferase, dopamine, and sleep-wake regulation. , 2015, Sleep medicine reviews.

[38]  Gerald M. Rubin,et al.  Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body , 2015, Current Biology.

[39]  Gero Miesenböck,et al.  Neuronal Machinery of Sleep Homeostasis in Drosophila , 2014, Neuron.

[40]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[41]  G. Tononi,et al.  Correlates of sleep and waking in Drosophila melanogaster. , 2000, Science.

[42]  Michael N Nitabach,et al.  Electrical Silencing of Drosophila Pacemaker Neurons Stops the Free-Running Circadian Clock , 2002, Cell.

[43]  Kei Ito,et al.  Identification of a dopamine pathway that regulates sleep and arousal in Drosophila , 2012, Nature Neuroscience.

[44]  Haojiang Luan,et al.  Refined Spatial Manipulation of Neuronal Function by Combinatorial Restriction of Transgene Expression , 2006, Neuron.

[45]  Michael Bate,et al.  Altered Electrical Properties in DrosophilaNeurons Developing without Synaptic Transmission , 2001, The Journal of Neuroscience.

[46]  G. Rubin,et al.  Refinement of Tools for Targeted Gene Expression in Drosophila , 2010, Genetics.