Neurogenetic dissection of the Drosophila lateral horn reveals major outputs, diverse behavioural functions, and interactions with the mushroom body

Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior.

[1]  O. Sporns The connectome , 2020, New Oxford Textbook of Psychiatry.

[2]  John D. Storey,et al.  False Discovery Rate , 2020, International Encyclopedia of Statistical Science.

[3]  James D. Manton,et al.  The natverse: a versatile computational toolbox to combine and analyse neuroanatomical data , 2014, bioRxiv.

[4]  I. G. Kadow Decision letter: Functional and anatomical specificity in a higher olfactory centre , 2019 .

[5]  G. Rubin,et al.  Communication from Learned to Innate Olfactory Processing Centers Is Required for Memory Retrieval in Drosophila , 2018, Neuron.

[6]  Gregory S.X.E. Jefferis,et al.  Neural circuit basis of aversive odour processing in Drosophila from sensory input to descending output , 2018 .

[7]  Nélia Varela,et al.  Avoidance response to CO2 in the lateral horn , 2018, bioRxiv.

[8]  James M. Jeanne,et al.  The Organization of Projections from Olfactory Glomeruli onto Higher-Order Neurons , 2018, Neuron.

[9]  Paola Patella,et al.  Functional Maps of Mechanosensory Features in the Drosophila Brain , 2018, Current Biology.

[10]  M. Dickinson,et al.  The functional organization of descending sensory-motor pathways in Drosophila , 2017, bioRxiv.

[11]  Philipp Schlegel,et al.  Learning from connectomics on the fly. , 2017, Current opinion in insect science.

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

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

[14]  Louis K. Scheffer,et al.  A connectome of a learning and memory center in the adult Drosophila brain , 2017, eLife.

[15]  Casey M. Schneider-Mizell,et al.  Conserved neural circuit structure across Drosophila larval development revealed by comparative connectomics , 2017, bioRxiv.

[16]  L. F. Abbott,et al.  The complete connectome of a learning and memory centre in an insect brain , 2017, Nature.

[17]  Eric T. Trautman,et al.  A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster , 2017, Cell.

[18]  L. Abbott,et al.  Representations of Novelty and Familiarity in a Mushroom Body Compartment , 2017, Cell.

[19]  H. Iftikhar,et al.  The role of the Drosophila lateral horn in olfactory information processing and behavioral response. , 2017, Journal of insect physiology.

[20]  Kristin Branson,et al.  Moonwalker Descending Neurons Mediate Visually Evoked Retreat in Drosophila , 2017, Current Biology.

[21]  Kristin Scott,et al.  Long-range projection neurons in the taste circuit of Drosophila , 2017, eLife.

[22]  William F Tobin,et al.  Wiring variations that enable and constrain neural computation in a sensory microcircuit , 2017, bioRxiv.

[23]  Michael B. Reiser,et al.  Visual projection neurons in the Drosophila lobula link feature detection to distinct behavioral programs , 2016, eLife.

[24]  M. Dacke,et al.  Fecal-Derived Phenol Induces Egg-Laying Aversion in Drosophila , 2016, Current Biology.

[25]  Yoshinori Aso,et al.  Dopaminergic neurons write and update memories with cell-type-specific rules , 2016, eLife.

[26]  Rachel I. Wilson,et al.  Behavior Reveals Selective Summation and Max Pooling among Olfactory Processing Channels , 2016, Neuron.

[27]  A. Kamikouchi,et al.  Organization of projection neurons and local neurons of the primary auditory center in the fruit fly Drosophila melanogaster , 2016, The Journal of comparative neurology.

[28]  Rafael Cantera,et al.  Synaptic circuitry of identified neurons in the antennal lobe of Drosophila melanogaster , 2016, The Journal of comparative neurology.

[29]  Vikas Bhandawat,et al.  Organization of descending neurons in Drosophila melanogaster , 2016, Scientific Reports.

[30]  Gregory S.X.E. Jefferis,et al.  NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases , 2016, Neuron.

[31]  Raphael Cohn,et al.  Coordinated and Compartmentalized Neuromodulation Shapes Sensory Processing in Drosophila , 2015, Cell.

[32]  Gerald M. Rubin,et al.  Heterosynaptic Plasticity Underlies Aversive Olfactory Learning in Drosophila , 2015, Neuron.

[33]  M. Knaden,et al.  Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit , 2015, PLoS biology.

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

[35]  Vikas Bhandawat,et al.  Odor-identity dependent motor programs underlie behavioral responses to odors , 2015, eLife.

[36]  Cyrille C. Girardin,et al.  Connecting Neural Codes with Behavior in the Auditory System of Drosophila , 2015, Neuron.

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

[38]  V. Ruta,et al.  Multimodal Chemosensory Circuits Controlling Male Courtship in Drosophila , 2015, Neuron.

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

[40]  Julie H. Simpson,et al.  A neural command circuit for grooming movement control , 2015, eLife.

[41]  Gerald M. Rubin,et al.  Plasticity-driven individualization of olfactory coding in mushroom body output neurons , 2015, Nature.

[42]  Aljoscha Nern,et al.  Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system , 2015, Proceedings of the National Academy of Sciences.

[43]  Johannes Felsenberg,et al.  Activity of Defined Mushroom Body Output Neurons Underlies Learned Olfactory Behavior in Drosophila , 2015, Neuron.

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

[45]  Lindsey J. Macpherson,et al.  Temperature representation in the Drosophila brain , 2015, Nature.

[46]  S. Liberles,et al.  Aversion and Attraction through Olfaction , 2015, Current Biology.

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

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

[49]  G. Rubin,et al.  Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits , 2014, The Journal of comparative neurology.

[50]  Markus Knaden,et al.  Decoding odor quality and intensity in the Drosophila brain , 2014, eLife.

[51]  D. Floreano,et al.  Mechanosensory Interactions Drive Collective Behaviour in Drosophila , 2014, Nature.

[52]  David J. Anderson,et al.  Toward a Science of Computational Ethology , 2014, Neuron.

[53]  R. Hen,et al.  The participation of cortical amygdala in innate, odor-driven behavior , 2014, Nature.

[54]  B. Brembs,et al.  Sub-strains of Drosophila Canton-S differ markedly in their locomotor behavior. , 2014, F1000Research.

[55]  Torsten Rohlfing,et al.  Combining genome-scale Drosophila 3 D neuroanatomical data by bridging template brains , 2014 .

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

[57]  Barry J. Dickson,et al.  Neuronal Control of Drosophila Walking Direction , 2014, Science.

[58]  Andrew C. Lin,et al.  Sparse, Decorrelated Odor Coding in the Mushroom Body Enhances Learned Odor Discrimination , 2014, Nature Neuroscience.

[59]  Julie H. Simpson,et al.  A Systematic Nomenclature for the Insect Brain , 2014, Neuron.

[60]  S. Zeng,et al.  Parallel pathways convey olfactory information with opposite polarities in Drosophila , 2014, Proceedings of the National Academy of Sciences.

[61]  Michael H. Dickinson,et al.  Plume-Tracking Behavior of Flying Drosophila Emerges from a Set of Distinct Sensory-Motor Reflexes , 2014, Current Biology.

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

[63]  U. Homberg,et al.  Organization and functional roles of the central complex in the insect brain. , 2014, Annual review of entomology.

[64]  Rachel I. Wilson,et al.  Stereotyped connectivity and computations in higher-order olfactory neurons , 2013, Nature Neuroscience.

[65]  Gregory S.X.E. Jefferis,et al.  A Bidirectional Circuit Switch Reroutes Pheromone Signals in Male and Female Brains , 2013, Cell.

[66]  Glenn C. Turner,et al.  Integration of the olfactory code across dendritic claws of single mushroom body neurons , 2013, Nature Neuroscience.

[67]  Gero Miesenböck,et al.  Odor Discrimination in Drosophila: From Neural Population Codes to Behavior , 2013, Neuron.

[68]  Liang Liang,et al.  GABAergic Projection Neurons Route Selective Olfactory Inputs to Specific Higher-Order Neurons , 2013, Neuron.

[69]  Louis K. Scheffer,et al.  A visual motion detection circuit suggested by Drosophila connectomics , 2013, Nature.

[70]  Michael B. Reiser,et al.  Contributions of the 12 Neuron Classes in the Fly Lamina to Motion Vision , 2013, Neuron.

[71]  Yoshinori Aso,et al.  Essential Role of the Mushroom Body in Context-Dependent CO2 Avoidance in Drosophila , 2013, Current Biology.

[72]  Liqun Luo,et al.  Specific Kinematics and Motor-Related Neurons for Aversive Chemotaxis in Drosophila , 2013, Current Biology.

[73]  Yan Zhu,et al.  The Drosophila visual system , 2013, Cell adhesion & migration.

[74]  Ann-Shyn Chiang,et al.  Parallel Neural Pathways Mediate CO2 Avoidance Responses in Drosophila , 2013, Science.

[75]  Rachel I. Wilson,et al.  Glutamate is an inhibitory neurotransmitter in the Drosophila olfactory system , 2013, Proceedings of the National Academy of Sciences.

[76]  L. Abbott,et al.  Random Convergence of Olfactory Inputs in the Drosophila Mushroom Body , 2013, Nature.

[77]  P. Shen,et al.  Neuropeptide-gated perception of appetitive olfactory inputs in Drosophila larvae. , 2013, Cell reports.

[78]  Minrong Ai,et al.  Dedicated olfactory neurons mediating attraction behavior to ammonia and amines in Drosophila , 2013, Proceedings of the National Academy of Sciences.

[79]  M. Hilker,et al.  Interactions of Carbon Dioxide and Food Odours in Drosophila: Olfactory Hedonics and Sensory Neuron Properties , 2013, PloS one.

[80]  Kei Ito,et al.  Organization of antennal lobe‐associated neurons in adult Drosophila melanogaster brain , 2012, The Journal of comparative neurology.

[81]  Markus Knaden,et al.  A Conserved Dedicated Olfactory Circuit for Detecting Harmful Microbes in Drosophila , 2012, Cell.

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

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

[84]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[85]  M. Stopfer,et al.  Functional Analysis of a Higher Olfactory Center, the Lateral Horn , 2012, The Journal of Neuroscience.

[86]  T. Miyashita,et al.  Mg2+ Block of Drosophila NMDA Receptors Is Required for Long-Term Memory Formation and CREB-Dependent Gene Expression , 2012, Neuron.

[87]  Kristin Scott,et al.  Contact Chemoreceptors Mediate Male-Male Repulsion and Male-Female Attraction during Drosophila Courtship , 2012, Cell.

[88]  Charles D. Hansen,et al.  FluoRender: An application of 2D image space methods for 3D and 4D confocal microscopy data visualization in neurobiology research , 2012, 2012 IEEE Pacific Visualization Symposium.

[89]  Julie H. Simpson,et al.  Genetic Manipulation of Genes and Cells in the Nervous System of the Fruit Fly , 2011, Neuron.

[90]  G. Jefferis,et al.  An olfactory receptor for food-derived odours promotes male courtship in Drosophila , 2011, Nature.

[91]  Dan D. Stettler,et al.  Driving Opposing Behaviors with Ensembles of Piriform Neurons , 2011, Cell.

[92]  Robert A. A. Campbell,et al.  Cellular-Resolution Population Imaging Reveals Robust Sparse Coding in the Drosophila Mushroom Body , 2011, The Journal of Neuroscience.

[93]  G. Rubin,et al.  Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila , 2011, Nature Neuroscience.

[94]  Yang Yu,et al.  Automated high speed stitching of large 3D microscopic images , 2011, 2011 IEEE International Symposium on Biomedical Imaging: From Nano to Macro.

[95]  G. Laurent,et al.  Normalization for Sparse Encoding of Odors by a Wide-Field Interneuron , 2011, Science.

[96]  Ian R. Wickersham,et al.  Cortical representations of olfactory input by trans-synaptic tracing , 2011, Nature.

[97]  S. R. Datta,et al.  Distinct representations of olfactory information in different cortical centres , 2011, Nature.

[98]  Guan-Yu Chen,et al.  Three-Dimensional Reconstruction of Brain-wide Wiring Networks in Drosophila at Single-Cell Resolution , 2011, Current Biology.

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

[100]  Jai Y. Yu,et al.  Sexual Dimorphism in the Fly Brain , 2010, Current Biology.

[101]  E. Yaksi,et al.  Electrical Coupling between Olfactory Glomeruli , 2010, Neuron.

[102]  B. Sacchetti,et al.  Role of Secondary Sensory Cortices in Emotional Memory Storage and Retrieval in Rats , 2010, Science.

[103]  Yisheng He,et al.  A Complete Developmental Sequence of a Drosophila Neuronal Lineage as Revealed by Twin-Spot MARCM , 2010, PLoS biology.

[104]  Renaud Gaujoux,et al.  A flexible R package for nonnegative matrix factorization , 2010, BMC Bioinformatics.

[105]  M. Dickinson,et al.  A New Chamber for Studying the Behavior of Drosophila , 2010, PloS one.

[106]  David J. Anderson,et al.  Identification of an aggression-promoting pheromone and its receptor neurons in Drosophila , 2009, Nature.

[107]  G. Miesenböck,et al.  Writing Memories with Light-Addressable Reinforcement Circuitry , 2009, Cell.

[108]  J. Carlson,et al.  Olfactory Perception: Receptors, Cells, and Circuits , 2009, Cell.

[109]  Nicolas Y. Masse,et al.  Olfactory Information Processing in Drosophila , 2009, Current Biology.

[110]  Rachel I. Wilson,et al.  Origins of correlated activity in an olfactory circuit , 2009, Nature Neuroscience.

[111]  Ronald L. Davis,et al.  Frontiers in Neural Circuits Neural Circuits , 2022 .

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

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

[114]  Michael H. Dickinson,et al.  A modular display system for insect behavioral neuroscience , 2008, Journal of Neuroscience Methods.

[115]  B. Dickson,et al.  A single class of olfactory neurons mediates behavioural responses to a Drosophila sex pheromone , 2007, Nature.

[116]  L. Vosshall,et al.  Influence of odorant receptor repertoire on odor perception in humans and fruit flies , 2007, Proceedings of the National Academy of Sciences.

[117]  L. Luo,et al.  Comprehensive Maps of Drosophila Higher Olfactory Centers: Spatially Segregated Fruit and Pheromone Representation , 2007, Cell.

[118]  S. Waddell,et al.  Sequential Use of Mushroom Body Neuron Subsets during Drosophila Odor Memory Processing , 2007, Neuron.

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

[120]  M. Dickinson,et al.  Free-flight responses of Drosophila melanogaster to attractive odors , 2006, Journal of Experimental Biology.

[121]  Barry J. Dickson,et al.  Molecular, Anatomical, and Functional Organization of the Drosophila Olfactory System , 2005, Current Biology.

[122]  Leslie B. Vosshall,et al.  Genetic and Functional Subdivision of the Drosophila Antennal Lobe , 2005, Current Biology.

[123]  David J. Anderson,et al.  A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila , 2004, Nature.

[124]  Kristin Scott,et al.  Taste Representations in the Drosophila Brain , 2004, Cell.

[125]  Kei Ito,et al.  Integration of Chemosensory Pathways in the Drosophila Second-Order Olfactory Centers , 2004, Current Biology.

[126]  Torsten Rohlfing,et al.  Nonrigid image registration in shared-memory multiprocessor environments with application to brains, breasts, and bees , 2003, IEEE Transactions on Information Technology in Biomedicine.

[127]  Richard Axel,et al.  Spatial Representation of the Glomerular Map in the Drosophila Protocerebrum , 2002, Cell.

[128]  L. Luo,et al.  Representation of the Glomerular Olfactory Map in the Drosophila Brain , 2002, Cell.

[129]  R. Stocker,et al.  A central neural circuit for experience-independent olfactory and courtship behavior in Drosophila melanogaster , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[130]  R. Davis,et al.  The Role of Drosophila Mushroom Body Signaling in Olfactory Memory , 2001, Science.

[131]  Tim Tully,et al.  Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory , 2001, Nature.

[132]  R. C Cannon,et al.  An on-line archive of reconstructed hippocampal neurons , 1998, Journal of Neuroscience Methods.

[133]  K. Svoboda,et al.  Genetic Dissection of Neural Circuits: A Decade of Progress , 2018, Neuron.

[134]  Aurel A Lazar,et al.  Figures and figure supplements Projection neurons in Drosophila antennal lobes signal the acceleration of odor concentrations , 2015 .

[135]  Yevgeniy B. Slutskiy,et al.  Projection neurons in Drosophila antennal lobes signal the acceleration of odor concentrations , 2015, eLife.