Neural circuits driving larval locomotion in Drosophila

More than 30 years of studies into Drosophila melanogaster neurogenesis have revealed fundamental insights into our understanding of axon guidance mechanisms, neural differentiation, and early cell fate decisions. What is less understood is how a group of neurons from disparate anterior-posterior axial positions, lineages and developmental periods of neurogenesis coalesce to form a functional circuit. Using neurogenetic techniques developed in Drosophila it is now possible to study the neural substrates of behavior at single cell resolution. New mapping tools described in this review, allow researchers to chart neural connectivity to better understand how an anatomically simple organism performs complex behaviors.

[1]  Takako Morimoto,et al.  A Group of Segmental Premotor Interneurons Regulates the Speed of Axial Locomotion in Drosophila Larvae , 2014, Current Biology.

[2]  Marta Zlatic,et al.  Divergent Connectivity of Homologous Command-like Neurons Mediates Segment-Specific Touch Responses in Drosophila , 2017, Neuron.

[3]  M. Monastirioti,et al.  Octopamine immunoreactivity in the fruit fly Drosophila melanogaster , 1995, The Journal of comparative neurology.

[4]  E. Marder,et al.  Principles of rhythmic motor pattern generation. , 1996, Physiological reviews.

[5]  Stefan R. Pulver,et al.  Imaging fictive locomotor patterns in larval Drosophila , 2015, Journal of neurophysiology.

[6]  G. E. Goslow,et al.  The cat step cycle: Hind limb joint angles and muscle lengths during unrestrained locomotion , 1973, Journal of morphology.

[7]  M. Bate,et al.  The embryonic development of larval muscles in Drosophila. , 1990, Development.

[8]  E. Marder.  Motor pattern generation , 2000, Current Opinion in Neurobiology.

[9]  B. Dickson,et al.  Genome-scale functional characterization of Drosophila developmental enhancers in vivo , 2014, Nature.

[10]  Stefan R. Pulver,et al.  Selective Inhibition Mediates the Sequential Recruitment of Motor Pools , 2016, Neuron.

[11]  R. Levine,et al.  Crawling motor patterns induced by pilocarpine in isolated larval nerve cords of Manduca sexta. , 1996, Journal of neurophysiology.

[12]  A. Cardona,et al.  A circuit mechanism for the propagation of waves of muscle contraction in Drosophila , 2016, eLife.

[13]  Eve Marder,et al.  Animal-to-Animal Variability in Motor Pattern Production in Adults and during Growth , 2005, The Journal of Neuroscience.

[14]  Cornelia I Bargmann,et al.  The Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) initiative and neurology. , 2014, JAMA neurology.

[15]  John B. Thomas,et al.  A subset of interneurons required for Drosophila larval locomotion , 2016, Molecular and Cellular Neuroscience.

[16]  A. Tsubouchi,et al.  Larval Defense against Attack from Parasitoid Wasps Requires Nociceptive Neurons , 2013, PloS one.

[17]  Kendal Broadie,et al.  Electrophysiological analysis of synaptic transmission in central neurons of Drosophila larvae. , 2002, Journal of neurophysiology.

[18]  Stefan R. Pulver,et al.  Temporal dynamics of neuronal activation by Channelrhodopsin-2 and TRPA1 determine behavioral output in Drosophila larvae. , 2009, Journal of neurophysiology.

[19]  Farhan Mohammad,et al.  Optogenetic inhibition of behavior with anion channelrhodopsins , 2017, Nature Methods.

[20]  Casey M. Schneider-Mizell,et al.  Quantitative neuroanatomy for connectomics in Drosophila , 2015, bioRxiv.

[21]  Trim9 Regulates Activity-Dependent Fine-Scale Topography in Drosophila , 2014, Current Biology.

[22]  John B. Thomas,et al.  A sensory feedback circuit coordinates muscle activity in Drosophila , 2007, Molecular and Cellular Neuroscience.

[23]  C. H. Green,et al.  Organization and patterns of inter- and intraspecific variation in the behaviour of Drosophila larvae , 1983, Animal Behaviour.

[24]  K. Broadie,et al.  Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects , 1995, Neuron.

[25]  Aravinthan D. T. Samuel,et al.  The wiring diagram of a glomerular olfactory system , 2016, bioRxiv.

[26]  K. Pearson,et al.  Discharge patterns of coxal levator and depressor motoneurones of the cockroach, Periplaneta americana. , 1970, The Journal of experimental biology.

[27]  O. Kiehn.  Development and functional organization of spinal locomotor circuits , 2011, Current Opinion in Neurobiology.

[28]  Stephen J. Eglen,et al.  Neural circuits for peristaltic wave propagation in crawling Drosophila larvae: analysis and modeling , 2013, Front. Comput. Neurosci..

[29]  James W. Truman,et al.  Identification of excitatory premotor interneurons which regulate local muscle contraction during Drosophila larval locomotion , 2016, Scientific Reports.

[30]  G. Rubin,et al.  Genetic Reagents for Making Split-GAL4 Lines in Drosophila , 2017, Genetics.

[31]  Ben Sutcliffe,et al.  Facilitating Neuron-Specific Genetic Manipulations in Drosophila melanogaster Using a Split GAL4 Repressor , 2017, Genetics.

[32]  Hiroshi Kohsaka,et al.  Optical Dissection of Neural Circuits Responsible for Drosophila Larval Locomotion with Halorhodopsin , 2011, PloS one.

[33]  Mark Johnson,et al.  Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango , 2017, Neuron.

[34]  H. Kohsaka,et al.  Gap Junction–Mediated Signaling from Motor Neurons Regulates Motor Generation in the Central Circuits of Larval Drosophila , 2017, The Journal of Neuroscience.

[35]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[36]  H. Kohsaka,et al.  Serotonin and Downstream Leucokinin Neurons Modulate Larval Turning Behavior in Drosophila , 2014, The Journal of Neuroscience.

[37]  Stephan Gerhard,et al.  Astrocytic glutamate transport regulates a Drosophila CNS synapse that lacks astrocyte ensheathment , 2016, The Journal of comparative neurology.

[38]  E. Marder,et al.  Central pattern generators and the control of rhythmic movements , 2001, Current Biology.

[39]  Matthias Landgraf,et al.  Midline Signalling Systems Direct the Formation of a Neural Map by Dendritic Targeting in the Drosophila Motor System , 2009, PLoS biology.

[40]  R. Levine,et al.  Role of intrinsic properties in Drosophila motoneuron recruitment during fictive crawling. , 2010, Journal of neurophysiology.

[41]  Barry J. Dickson,et al.  The VT GAL4, LexA, and split-GAL4 driver line collections for targeted expression in the Drosophila nervous system , 2017, bioRxiv.

[42]  C. Reggiani,et al.  From action potential to contraction: neural control and excitation-contraction coupling in larval muscles of Drosophila. , 2009, Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.

[43]  Optogenetic Neuronal Silencing in Drosophila during Visual Processing , 2017, Scientific Reports.

[44]  W. Grueber,et al.  Development of the embryonic and larval peripheral nervous system of Drosophila , 2014, Wiley interdisciplinary reviews. Developmental biology.

[45]  Donghyung Lee,et al.  Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT) , 2017, eLife.

[46]  J. Halbertsma,et al.  Changes in leg movements and muscle activity with speed of locomotion and mode of progression in humans. , 1985, Acta physiologica Scandinavica.

[47]  Jimena Berni,et al.  Genetic Dissection of a Regionally Differentiated Network for Exploratory Behavior in Drosophila Larvae , 2015, Current Biology.

[48]  M. Landgraf,et al.  Development of Drosophila motoneurons: specification and morphology. , 2006, Seminars in cell & developmental biology.

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

[50]  Hiroshi Kohsaka,et al.  Neural Circuits Underlying Fly Larval Locomotion , 2017, Current pharmaceutical design.

[51]  Stefan R. Pulver,et al.  Identification of Inhibitory Premotor Interneurons Activated at a Late Phase in a Motor Cycle during Drosophila Larval Locomotion , 2015, PloS one.

[52]  J. Dasen,et al.  Evolution of patterning systems and circuit elements for locomotion. , 2015, Developmental cell.

[53]  Matthias Landgraf,et al.  Even-Skipped+ Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude , 2015, Neuron.

[54]  Yuh Nung Jan,et al.  Peripheral multidendritic sensory neurons are necessary for rhythmic locomotion behavior in Drosophila larvae , 2007, Proceedings of the National Academy of Sciences.

[55]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[56]  D. Soll,et al.  Coordination and Modulation of Locomotion Pattern Generators in Drosophila Larvae: Effects of Altered Biogenic Amine Levels by the Tyramine β Hydroxlyase Mutation , 2006, The Journal of Neuroscience.

[57]  S. Grillner,et al.  Neuronal network generating locomotor behavior in lamprey: circuitry, transmitters, membrane properties, and simulation. , 1991, Annual review of neuroscience.

[58]  M. P. Nusbaum,et al.  A small-systems approach to motor pattern generation , 2002, Nature.

[59]  K. Kawakami,et al.  A novel conserved evx1 enhancer links spinal interneuron morphology and cis-regulation from fish to mammals. , 2009, Developmental biology.

[60]  Kristin Branson,et al.  Whole-central nervous system functional imaging in larval Drosophila , 2015, Nature Communications.

[61]  Matthias Landgraf,et al.  Charting the Drosophila neuropile: a strategy for the standardised characterisation of genetically amenable neurites. , 2003, Developmental biology.

[62]  J. Armstrong,et al.  Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons , 2015, PloS one.

[63]  C. Wegener,et al.  Neuroarchitecture of Aminergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster , 2007, PLoS ONE.

[64]  Shawn R. Lockery,et al.  Characterization of Drosophila Larval Crawling at the Level of Organism, Segment, and Somatic Body Wall Musculature , 2012, The Journal of Neuroscience.

[65]  Johannes D. Seelig,et al.  Angular velocity integration in a fly heading circuit , 2017, eLife.

[66]  S. Grillner.  On the generation of locomotion in the spinal dogfish , 2004, Experimental Brain Research.

[67]  Feng Zhang,et al.  Nociceptive Neurons Protect Drosophila Larvae from Parasitoid Wasps , 2007, Current Biology.

[68]  Alex Gomez-Marin,et al.  Role of the Subesophageal Zone in Sensorimotor Control of Orientation in Drosophila Larva , 2015, Current Biology.

[69]  Feng Li,et al.  The complete connectome of a learning and memory centre in an insect brain , 2017, Nature.

[70]  Stefan R. Pulver,et al.  Independent Optical Excitation of Distinct Neural Populations , 2014, Nature Methods.

[71]  Doycho Karagyozov,et al.  Recording neural activity in unrestrained animals with 3D tracking two photon microscopy , 2017, bioRxiv.

[72]  M. Suster,et al.  Embryonic assembly of a central pattern generator without sensory input , 2002, Nature.

[73]  Sen-Lin Lai,et al.  Genetic mosaic with dual binary transcriptional systems in Drosophila , 2006, Nature Neuroscience.

[74]  Michael Bate,et al.  Electrophysiological Development of Central Neurons in theDrosophila Embryo , 1998, The Journal of Neuroscience.

[75]  Wei Zhang,et al.  Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation , 2012, Nature.

[76]  David J. Anderson,et al.  Optogenetic control of freely behaving adult Drosophila using a red-shifted channelrhodopsin , 2013, Nature Methods.

[77]  Simon G. Sprecher,et al.  The Serotonergic Central Nervous System of the Drosophila Larva: Anatomy and Behavioral Function , 2012, PloS one.

[78]  A. Gordus,et al.  Sensitive red protein calcium indicators for imaging neural activity , 2016, bioRxiv.

[79]  Casey M. Schneider-Mizell,et al.  Competitive Disinhibition Mediates Behavioral Choice and Sequences in Drosophila , 2016, Cell.

[80]  C. Rickert,et al.  Morphological Characterization of the Entire Interneuron Population Reveals Principles of Neuromere Organization in the Ventral Nerve Cord of Drosophila , 2011, The Journal of Neuroscience.

[81]  Kristin Branson,et al.  A multilevel multimodal circuit enhances action selection in Drosophila , 2015, Nature.

[82]  Matthias Landgraf,et al.  Structural Homeostasis: Compensatory Adjustments of Dendritic Arbor Geometry in Response to Variations of Synaptic Input , 2008, PLoS biology.

[83]  Ehud Y. Isacoff,et al.  Input-Specific Plasticity and Homeostasis at the Drosophila Larval Neuromuscular Junction , 2017, Neuron.

[84]  Hanchuan Peng,et al.  Atlas-builder software and the eNeuro atlas: resources for developmental biology and neuroscience , 2014, Development.

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

[86]  Marta Zlatic,et al.  Positional Cues in the Drosophila Nerve Cord: Semaphorins Pattern the Dorso-Ventral Axis , 2009, PLoS biology.

[87]  W. Kristan,et al.  A kinematic study of crawling behavior in the leech,Hirudo medicinalis , 1986, Journal of Comparative Physiology A.

[88]  H. Atwood.  PARALLEL `PHASIC' AND `TONIC' MOTOR SYSTEMS OF THE CRAYFISH ABDOMEN , 2008, Journal of Experimental Biology.

[89]  Fine-scale topography in sensory systems: insights from Drosophila and vertebrates , 2015, Journal of Comparative Physiology A.

[90]  Genetic reagents for making split-GAL4 lines in Drosophila , 2017 .

[91]  Stefan R. Pulver,et al.  Autonomous Circuitry for Substrate Exploration in Freely Moving Drosophila Larvae , 2012, Current Biology.

[92]  Marc Gershow,et al.  Two Alternating Motor Programs Drive Navigation in Drosophila Larva , 2011, PloS one.

[93]  J. Truman,et al.  The Role of the Prothoracic Gland in Determining Critical Weight for Metamorphosis in Drosophila melanogaster , 2005, Current Biology.

[94]  A. Tsubouchi,et al.  Dendritic Filopodia, Ripped Pocket, NOMPC, and NMDARs Contribute to the Sense of Touch in Drosophila Larvae , 2012, Current Biology.

[95]  Michael Bate,et al.  Hox genes and the regulation of movement in Drosophila , 2008, Developmental neurobiology.

[96]  Alex Gomez-Marin,et al.  Active sensation during orientation behavior in the Drosophila larva: more sense than luck , 2012, Current Opinion in Neurobiology.

[97]  Liang Liang,et al.  The Q System: A Repressible Binary System for Transgene Expression, Lineage Tracing, and Mosaic Analysis , 2010, Cell.

[98]  Casey M. Schneider-Mizell,et al.  Synaptic transmission parallels neuromodulation in a central food-intake circuit , 2016, bioRxiv.

[99]  L. Mendell,et al.  The size principle: a rule describing the recruitment of motoneurons. , 2005, Journal of neurophysiology.

[100]  L. Looger,et al.  Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall , 2010, Nature.

[101]  Marta Zlatic,et al.  Organization of the Drosophila larval visual circuit , 2017, bioRxiv.

[102]  Jan Felix Evers,et al.  The development of motor coordination in Drosophila embryos , 2008, Development.

[103]  T. Kitamoto.  Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. , 2001, Journal of neurobiology.

[104]  D. Merritt,et al.  Central projections of sensory neurons in the Drosophila embryo correlate with sensory modality, soma position, and proneural gene function , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.