The neuronal architecture of the mushroom body provides a logic for associative learning

We identified the neurons comprising the Drosophila mushroom body (MB), an associative center in invertebrate brains, and provide a comprehensive map describing their potential connections. Each of the 21 MB output neuron (MBON) types elaborates segregated dendritic arbors along the parallel axons of ∼2000 Kenyon cells, forming 15 compartments that collectively tile the MB lobes. MBON axons project to five discrete neuropils outside of the MB and three MBON types form a feedforward network in the lobes. Each of the 20 dopaminergic neuron (DAN) types projects axons to one, or at most two, of the MBON compartments. Convergence of DAN axons on compartmentalized Kenyon cell–MBON synapses creates a highly ordered unit that can support learning to impose valence on sensory representations. The elucidation of the complement of neurons of the MB provides a comprehensive anatomical substrate from which one can infer a functional logic of associative olfactory learning and memory. DOI: http://dx.doi.org/10.7554/eLife.04577.001

[1]  Schürmann Fw,et al.  [On the functional anatomy of the corpora pedunculata in insects (author's transl)]. , 1974 .

[2]  W. Harris,et al.  Conditioned behavior in Drosophila melanogaster. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[3]  F W Schürmann,et al.  [On the functional anatomy of the corpora pedunculata in insects (author's transl)]. , 1974, Experimental brain research.

[4]  R. W. Siegel,et al.  Conditioned responses in courtship behavior of normal and mutant Drosophila. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[5]  W. Quinn,et al.  Reward learning in normal and mutant Drosophila. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

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

[7]  J. Hirsh,et al.  Regulation of the Drosophila dopa decarboxylase gene in neuronal and glial cells. , 1987, Genes & development.

[8]  Konrad Basler,et al.  Organizing activity of wingless protein in Drosophila , 1993, Cell.

[9]  M Heisenberg,et al.  Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. , 1994, Science.

[10]  N. Baker,et al.  Evolution of proneural atonal expression during distinct regulatory phases in the developing Drosophila eye , 1996, Current Biology.

[11]  P. Salvaterra,et al.  Analysis of choline acetyltransferase protein in temperature sensitive mutant flies using newly generated monoclonal antibody , 1996, Neuroscience Research.

[12]  D. Yamamoto,et al.  The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. , 1997, Development.

[13]  N. Strausfeld,et al.  The organization of extrinsic neurons and their implications in the functional roles of the mushroom bodies in Drosophila melanogaster Meigen. , 1998, Learning & memory.

[14]  R. Davis,et al.  Tripartite mushroom body architecture revealed by antigenic markers. , 1998, Learning & memory.

[15]  B. Tabashnik,et al.  Development time and resistance to Bt crops , 1999, Nature.

[16]  P. Hiesinger,et al.  Three‐dimensional reconstruction of the antennal lobe in Drosophila melanogaster , 1999, The Journal of comparative neurology.

[17]  L. Luo,et al.  Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast. , 1999, Development.

[18]  Li Liu,et al.  Context generalization in Drosophila visual learning requires the mushroom bodies , 1999, Nature.

[19]  W. Quinn,et al.  The amnesiac Gene Product Is Expressed in Two Neurons in the Drosophila Brain that Are Critical for Memory , 2000, Cell.

[20]  J. Hirsh,et al.  Ectopic G-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster , 2000, Current Biology.

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

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

[23]  Glenn C. Turner,et al.  Oscillations and Sparsening of Odor Representations in the Mushroom Body , 2002, Science.

[24]  George H. Patterson,et al.  A Photoactivatable GFP for Selective Photolabeling of Proteins and Cells , 2002, Science.

[25]  Gilles Laurent,et al.  Olfactory network dynamics and the coding of multidimensional signals , 2002, Nature Reviews Neuroscience.

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

[27]  R. Strauss The central complex and the genetic dissection of locomotor behaviour , 2002, Current Opinion in Neurobiology.

[28]  M. Heisenberg,et al.  Dopamine and Octopamine Differentiate between Aversive and Appetitive Olfactory Memories in Drosophila , 2003, The Journal of Neuroscience.

[29]  N. Strausfeld,et al.  The mushroom bodies of Drosophila melanogaster: An immunocytological and golgi study of Kenyon cell organization in the calyces and lobes , 2003, Microscopy research and technique.

[30]  N. Strausfeld,et al.  A unique mushroom body substructure common to basal cockroaches and to termites , 2003, The Journal of comparative neurology.

[31]  Jay Hirsh,et al.  Targeted gene expression in Drosophila dopaminergic cells using regulatory sequences from tyrosine hydroxylase. , 2003, Journal of neurobiology.

[32]  Ann-Shyn Chiang,et al.  Development of the Drosophila mushroom bodies: elaboration, remodeling and spatial organization of dendrites in the calyx , 2003, Development.

[33]  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.

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

[35]  A. Borst,et al.  Neuronal architecture of the antennal lobe in Drosophila melanogaster , 1990, Cell and Tissue Research.

[36]  M. Heisenberg,et al.  Neuronal architecture of the central complex in Drosophila melanogaster , 2004, Cell and Tissue Research.

[37]  Ramón Huerta,et al.  Learning Classification in the Olfactory System of Insects , 2004, Neural Computation.

[38]  F. Schürmann Bemerkungen zur funktion der corpora pedunculata im gehirn der insekten aus morphologischer sicht , 1974, Experimental Brain Research.

[39]  Liliane Schoofs,et al.  SIFamide is a highly conserved neuropeptide: a comparative study in different insect species. , 2004, Biochemical and biophysical research communications.

[40]  Thomas Preat,et al.  Exclusive Consolidated Memory Phases in Drosophila , 2004, Science.

[41]  A. Fiala,et al.  Punishment Prediction by Dopaminergic Neurons in Drosophila , 2005, Current Biology.

[42]  Richard S. Sutton,et al.  Reinforcement Learning: An Introduction , 1998, IEEE Trans. Neural Networks.

[43]  W. Quinn,et al.  Classical conditioning and retention in normal and mutantDrosophila melanogaster , 1985, Journal of Comparative Physiology A.

[44]  J. Hirsh,et al.  Two Functional but Noncomplementing Drosophila Tyrosine Decarboxylase Genes , 2005, Journal of Biological Chemistry.

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

[46]  M. Heisenberg,et al.  Distinct memory traces for two visual features in the Drosophila brain , 2006, Nature.

[47]  G. Nagel,et al.  Light-Induced Activation of Distinct Modulatory Neurons Triggers Appetitive or Aversive Learning in Drosophila Larvae , 2006, Current Biology.

[48]  H. Aberle,et al.  The expression pattern of the Drosophila vesicular glutamate transporter: a marker protein for motoneurons and glutamatergic centers in the brain. , 2006, Gene expression patterns : GEP.

[49]  Ann-Shyn Chiang,et al.  A Map of Olfactory Representation in the Drosophila Mushroom Body , 2007, Cell.

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

[51]  G. Laurent,et al.  Hebbian STDP in mushroom bodies facilitates the synchronous flow of olfactory information in locusts , 2007, Nature.

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

[53]  L. Vosshall,et al.  Molecular architecture of smell and taste in Drosophila. , 2007, Annual review of neuroscience.

[54]  Nasser M. Nasrabadi,et al.  Pattern Recognition and Machine Learning , 2006, Technometrics.

[55]  K. Han,et al.  D1 Dopamine Receptor dDA1 Is Required in the Mushroom Body Neurons for Aversive and Appetitive Learning in Drosophila , 2007, The Journal of Neuroscience.

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

[57]  Tzumin Lee,et al.  Organization and Postembryonic Development of Glial Cells in the Adult Central Brain of Drosophila , 2008, The Journal of Neuroscience.

[58]  Glenn C. Turner,et al.  Olfactory representations by Drosophila mushroom body neurons. , 2008, Journal of neurophysiology.

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

[60]  Brian B. Avants,et al.  Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain , 2008, Medical Image Anal..

[61]  Barry J. Dickson,et al.  The Drosophila pheromone cVA activates a sexually dimorphic neural circuit , 2008, Nature.

[62]  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.

[63]  Manuel Guizar-Sicairos,et al.  Efficient subpixel image registration algorithms. , 2008, Optics letters.

[64]  Gilles Laurent,et al.  Testing Odor Response Stereotypy in the Drosophila Mushroom Body , 2008, Neuron.

[65]  P. Greengard,et al.  Writing Memories with Light-Addressable Reinforcement Circuitry , 2009, Cell.

[66]  Gaia Tavosanis,et al.  Synaptic organization in the adult Drosophila mushroom body calyx , 2009, The Journal of comparative neurology.

[67]  Shamik Dasgupta,et al.  A Neural Circuit Mechanism Integrating Motivational State with Memory Expression in Drosophila , 2009, Cell.

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

[69]  Charles D. Hansen,et al.  An interactive visualization tool for multi-channel confocal microscopy data in neurobiology research , 2009, IEEE Transactions on Visualization and Computer Graphics.

[70]  Ronald L. Davis,et al.  Eight Different Types of Dopaminergic Neurons Innervate the Drosophila Mushroom Body Neuropil: Anatomical and Physiological Heterogeneity , 2009, Front. Neural Circuits.

[71]  Yoshinori Aso,et al.  The Mushroom Body of Adult Drosophila Characterized by GAL4 Drivers , 2009, Journal of neurogenetics.

[72]  E. Buchner,et al.  The Wuerzburg Hybridoma Library against Drosophila Brain , 2009, Journal of neurogenetics.

[73]  Kei Ito,et al.  A map of octopaminergic neurons in the Drosophila brain , 2009, The Journal of comparative neurology.

[74]  Richard Axel,et al.  A dimorphic pheromone circuit in Drosophila from sensory input to descending output , 2010, Nature.

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

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

[77]  H. Tanimoto,et al.  Cellular configuration of single octopamine neurons in Drosophila , 2010, The Journal of comparative neurology.

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

[79]  E. Kravitz,et al.  Targeted Manipulation of Serotonergic Neurotransmission Affects the Escalation of Aggression in Adult Male Drosophila melanogaster , 2010, PloS one.

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

[81]  H. Tanimoto,et al.  Appetitive and Aversive Visual Learning in Freely Moving Drosophila , 2009, Front. Behav. Neurosci..

[82]  Kristin Scott,et al.  Limited taste discrimination in Drosophila , 2010, Proceedings of the National Academy of Sciences.

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

[84]  J. Armstrong,et al.  Building the central complex in Drosophila: The generation and development of distinct neural subsets , 2010, The Journal of comparative neurology.

[85]  Yoshinori Aso,et al.  Specific Dopaminergic Neurons for the Formation of Labile Aversive Memory , 2010, Current Biology.

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

[87]  S. Farris Are mushroom bodies cerebellum-like structures? , 2011, Arthropod structure & development.

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

[89]  Michael B. Reiser,et al.  Visual Place Learning in Drosophila melanogaster , 2011, Nature.

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

[91]  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.

[92]  Zhiyuan Lu,et al.  Different classes of input and output neurons reveal new features in microglomeruli of the adult Drosophila mushroom body calyx , 2012, The Journal of comparative neurology.

[93]  G. Laurent,et al.  Conditional modulation of spike-timing-dependent plasticity for olfactory learning , 2012, Nature.

[94]  Yoshinori Aso,et al.  Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability , 2012, PLoS genetics.

[95]  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.

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

[97]  Daryl M. Gohl,et al.  Layered reward signaling through octopamine and dopamine in Drosophila , 2012, Nature.

[98]  Nicholas J. Strausfeld,et al.  Arthropod Brains: Evolution, Functional Elegance, and Historical Significance , 2012 .

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

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

[101]  S. Waddell Reinforcement signalling in Drosophila; dopamine does it all after all , 2013, Current Opinion in Neurobiology.

[102]  Wanhe Li,et al.  Imaging a Population Code for Odor Identity in the Drosophila Mushroom Body , 2013, The Journal of Neuroscience.

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

[104]  S. Tomchik Dopaminergic Neurons Encode a Distributed, Asymmetric Representation of Temperature in Drosophila , 2013, The Journal of Neuroscience.

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

[106]  Andrew C. Lin,et al.  Different Kenyon Cell Populations Drive Learned Approach and Avoidance in Drosophila , 2013, Neuron.

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

[108]  Ann-Shyn Chiang,et al.  Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation , 2013, Proceedings of the National Academy of Sciences.

[109]  Hiromu Tanimoto,et al.  Two pairs of mushroom body efferent neurons are required for appetitive long-term memory retrieval in Drosophila. , 2013, Cell reports.

[110]  André Fiala,et al.  Localization of the Contacts Between Kenyon Cells and Aminergic Neurons in the Drosophila melanogaster Brain Using SplitGFP Reconstitution , 2013, The Journal of comparative neurology.

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

[112]  Hanchuan Peng,et al.  Clonal Development and Organization of the Adult Drosophila Central Brain , 2013, Current Biology.

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

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

[115]  Scott Waddell,et al.  Drosophila Learn Opposing Components of a Compound Food Stimulus , 2014, Current Biology.

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

[117]  G. Rubin,et al.  Shared mushroom body circuits underlie visual and olfactory memories in Drosophila , 2014, eLife.

[118]  M. Low,et al.  Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory , 2022 .