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The wiring diagram of a glomerular olfactory system

Matthew E Berck, Avinash Khandelwal, Lindsey Claus and 9 more

eLife · 2016 · CC BY

doi:10.7554/elife.14859

Abstract

The sense of smell enables animals to react to long-distance cues according to learned and innate valences. Here, we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe, an olfactory neuropil similar to the vertebrate olfactory bulb. We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn. A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse. LN-LN synaptic connections putatively implement a bistable gain control mechanism that either computes odor saliency through panglomerular inhibition, or allows some glomeruli to respond to faint aversive odors in the presence of strong appetitive odors. This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior.

References 79

  1. 1.

    Alon U. Network motifs: theory and experimental approaches. Nature Reviews. Genetics. 2007;8:450-461.

    Not in our library10.1038/nrg2102

  2. 2.
  3. 3.

    Balu R, Pressler RT, Strowbridge BW. Multiple modes of synaptic excitation of olfactory bulb granule cells. Journal of Neuroscience. 2007;27:5621-5632.

    Not in our library10.1523/jneurosci.4630-06.2007

  4. 4.
  5. 5.

    Bhandawat V, Olsen SR, Gouwens NW, Schlief ML, Wilson RI. Sensory processing in the Drosophila antennal lobe increases reliability and separability of ensemble odor representations. Nature Neuroscience. 2007;10:1474-1482.

    Not in our library10.1038/nn1976

  6. 6.

    Carandini M. From circuits to behavior: a bridge too far? Nature Neuroscience. 2012;15:507-509.

    Not in our library10.1038/nn.3043

  7. 7.

    Chou YH, Spletter ML, Yaksi E, Leong JC, Wilson RI, Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe. Nature Neuroscience. 2010;13:439-449.

    Not in our library10.1038/nn.2489

  8. 8.

    Cobb M. What and how do maggots smell? Biological Reviews. 1999;74:425-459.

    Not in our library10.1017/s0006323199005393

  9. 9.

    Dacks AM, Green DS, Root CM, Nighorn AJ, Wang JW. Serotonin modulates olfactory processing in the antennal lobe of Drosophila. Journal of Neurogenetics. 2009;23:366-377.

    Not in our library10.3109/01677060903085722

  10. 10.

    Daniels RW, Collins CA, Gelfand MV, Dant J, Brooks ES, Krantz DE, DiAntonio A. Increased expression of the Drosophila vesicular glutamate transporter leads to excess glutamate release and a compensatory decrease in quantal content. Journal of Neuroscience. 2004;24:10466-10474.

    Not in our library10.1523/jneurosci.3001-04.2004

  11. 11.

    Das A, Gupta T, Davla S, Prieto-Godino LL, Diegelmann S, Reddy OV, Raghavan KV, Reichert H, Lovick J, Hartenstein V. Neuroblast lineage-specific origin of the neurons of the Drosophila larval olfactory system. Developmental Biology. 2013;373:322-337.

    Not in our library10.1016/j.ydbio.2012.11.003

  12. 12.

    de Belle JS, Heisenberg M. Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. Science. 1994;263:692-695.

    Not in our library10.1126/science.8303280

  13. 13.

    Distler PG, Boeckh J. Synaptic connection between olfactory receptor cells and uniglomerular projection neurons in the antennal lobe of the American cockroach, Periplaneta americana. The Journal of Comparative Neurology. 1996;370:35-46.

    Not in our library10.1002/(sici)1096-9861(19960617)370:1<35::aid-cne4>3.0.co;2-m

  14. 14.

    Drobysheva D, Ameel K, Welch B, Ellison E, Chaichana K, Hoang B, Sharma S, Neckameyer W, Srinakevitch I, Murphy KJ, Schmid A. An optimized method for histological detection of dopaminergic neurons in Drosophila melanogaster. Journal of Histochemistry and Cytochemistry. 2008;56:1049-1063.

    Not in our library10.1369/jhc.2008.951137

  15. 15.
  16. 16.

    Fischbach K, Heisenberg M. Neurogenetics and behaviour in insects. Journal of Experimental Biology. 1984;112:65-93.

    Not in our library

  17. 17.

    Fishilevich E, Domingos AI, Asahina K, Naef F, Vosshall LB, Louis M. Chemotaxis behavior mediated by single larval olfactory neurons in Drosophila. Current Biology. 2005;15:2086-2096.

    Not in our library10.1016/j.cub.2005.11.016

  18. 18.

    Fişek M, Wilson RI. Stereotyped connectivity and computations in higher-order olfactory neurons. Nature Neuroscience. 2014;17:280-288.

    Not in our library10.1038/nn.3613

  19. 19.

    Friedrich RW, Korsching SI. Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging. Neuron. 1997;18:737-752.

    Not in our library10.1016/s0896-6273(00)80314-1

  20. 20.

    Gao XJ, Clandinin TR, Luo L. Extremely sparse olfactory inputs are sufficient to mediate innate aversion in Drosophila. PloS One. 2015;10:e14859.

    Not in our library10.1371/journal.pone.0125986

  21. 21.

    Gepner R, Mihovilovic Skanata M, Bernat NM, Kaplow M, Gershow M, Skanata MM. Computations underlying Drosophila photo-taxis, odor-taxis, and multi-sensory integration. eLife. 2015;4:e14859.

    Not in our library10.7554/elife.06229

  22. 22.

    Gerber B, Stocker RF. The Drosophila larva as a model for studying chemosensation and chemosensory learning: a review. Chemical Senses. 2007;32:65-89.

    Not in our library10.1093/chemse/bjl030

  23. 23.

    Gershow M, Berck M, Mathew D, Luo L, Kane EA, Carlson JR, Samuel AD. Controlling airborne cues to study small animal navigation. Nature Methods. 2012;9:290-296.

    Not in our library10.1038/nmeth.1853

  24. 24.

    Gomez-Marin A, Stephens GJ, Louis M. Active sampling and decision making in Drosophila chemotaxis. Nature Communications. 2011;2:441.

    Not in our library10.1038/ncomms1455

  25. 25.

    Gouwens NW, Wilson RI. Signal propagation in Drosophila central neurons. Journal of Neuroscience. 2009;29:6239-6249.

    Not in our library10.1523/jneurosci.0764-09.2009

  26. 26.

    Haddad R, Khan R, Takahashi YK, Mori K, Harel D, Sobel N. A metric for odorant comparison. Nature Methods. 2008;5:425-429.

    Not in our library10.1038/nmeth.1197

  27. 27.

    Haddad R, Weiss T, Khan R, Nadler B, Mandairon N, Bensafi M, Schneidman E, Sobel N. Global features of neural activity in the olfactory system form a parallel code that predicts olfactory behavior and perception. Journal of Neuroscience. 2010;30:9017-9026.

    Not in our library10.1523/jneurosci.0398-10.2010

  28. 28.

    Heisenberg M, Borst A, Wagner S, Byers D. Drosophila mushroom body mutants are deficient in olfactory learning. Journal of Neurogenetics. 1985;2:1-30.

    Not in our library10.3109/01677068509100140

  29. 29.

    Hernandez-Nunez L, Belina J, Klein M, Si G, Claus L, Carlson JR, Samuel AD. Reverse-correlation analysis of navigation dynamics in Drosophila larva using optogenetics. eLife. 2015;4:e14859.

    Not in our library10.7554/elife.06225

  30. 30.

    Kim AJ, Lazar AA, Slutskiy YB. Projection neurons in Drosophila antennal lobes signal the acceleration of odor concentrations. eLife. 2015;4:e14859.

    Not in our library10.7554/elife.06651

  31. 31.

    Kreher SA, Mathew D, Kim J, Carlson JR. Translation of sensory input into behavioral output via an olfactory system. Neuron. 2008;59:110-124.

    Not in our library10.1016/j.neuron.2008.06.010

  32. 32.

    Lei H, Christensen TA, Hildebrand JG. Local inhibition modulates odor-evoked synchronization of glomerulus-specific output neurons. Nature Neuroscience. 2002;5:557-565.

    Not in our library10.1038/nn859

  33. 33.

    Li HH, Kroll JR, Lennox SM, Ogundeyi O, Jeter J, Depasquale G, Truman JW. A GAL4 driver resource for developmental and behavioral studies on the larval CNS of Drosophila. Cell Reports. 2014;8:897-908.

    Not in our library10.1016/j.celrep.2014.06.065

  34. 34.

    Liang L, Li Y, Potter CJ, Yizhar O, Deisseroth K, Tsien RW, Luo L. GABAergic projection neurons route selective olfactory inputs to specific higher-order neurons. Neuron. 2013;79:917-931.

    Not in our library10.1016/j.neuron.2013.06.014

  35. 35.

    Linster C, Smith BH. A computational model of the response of honey bee antennal lobe circuitry to odor mixtures: overshadowing, blocking and unblocking can arise from lateral inhibition. Behavioural Brain Research. 1997;87:1-14.

    Not in our library10.1016/s0166-4328(96)02271-1

  36. 36.

    Liu WW, Wilson RI. Glutamate is an inhibitory neurotransmitter in the Drosophila olfactory system. Proceedings of the National Academy of Sciences of the United States of America. 2013;110:10294-10299.

    Not in our library10.1073/pnas.1220560110

  37. 37.

    Louis M, Huber T, Benton R, Sakmar TP, Vosshall LB. Bilateral olfactory sensory input enhances chemotaxis behavior. Nature Neuroscience. 2008;11:187-199.

    Not in our library10.1038/nn2031

  38. 38.

    Luo SX, Axel R, Abbott LF. Generating sparse and selective third-order responses in the olfactory system of the fly. Proceedings of the National Academy of Sciences of the United States of America. 2010;107:10713-10718.

    Not in our library10.1073/pnas.1005635107

  39. 39.

    Manning L, Heckscher ES, Purice MD, Roberts J, Bennett AL, Kroll JR, Pollard JL, Strader ME, Lupton JR, Dyukareva AV, Doan PN, Bauer DM, Wilbur AN, Tanner S, Kelly JJ, Lai SL, Tran KD, Kohwi M, Laverty TR, Pearson JC, Crews ST, Rubin GM, Doe CQ. A resource for manipulating gene expression and analyzing cis-regulatory modules in the Drosophila CNS. Cell Reports. 2012;2:1002-1013.

    Not in our library10.1016/j.celrep.2012.09.009

  40. 40.

    Masuda-Nakagawa LM, Gendre N, O'Kane CJ, Stocker RF. Localized olfactory representation in mushroom bodies of Drosophila larvae. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:10314-10319.

    Not in our library10.1073/pnas.0900178106

  41. 41.

    Mathew D, Martelli C, Kelley-Swift E, Brusalis C, Gershow M, Samuel AD, Emonet T, Carlson JR. Functional diversity among sensory receptors in a Drosophila olfactory circuit. Proceedings of the National Academy of Sciences of the United States of America. 2013;110:E2134-E2143.

    Not in our library10.1073/pnas.1306976110

  42. 42.

    Michels B, Chen YC, Saumweber T, Mishra D, Tanimoto H, Schmid B, Engmann O, Gerber B. Cellular site and molecular mode of synapsin action in associative learning. Learning & Memory. 2011;18:332-344.

    Not in our library10.1101/lm.2101411

  43. 43.

    Montague SA, Mathew D, Carlson JR. Similar odorants elicit different behavioral and physiological responses, some supersustained. Journal of Neuroscience. 2011;31:7891-7899.

    Not in our library10.1523/jneurosci.6254-10.2011

  44. 44.

    Nagayama S, Takahashi YK, Yoshihara Y, Mori K. Mitral and tufted cells differ in the decoding manner of odor maps in the rat olfactory bulb. Journal of Neurophysiology. 2004;91:2532-2540.

    Not in our library10.1152/jn.01266.2003

  45. 45.

    Nagel KI, Hong EJ, Wilson RI. Synaptic and circuit mechanisms promoting broadband transmission of olfactory stimulus dynamics. Nature Neuroscience. 2015;18:56-65.

    Not in our library10.1038/nn.3895

  46. 46.

    Nagel KI, Wilson RI. Biophysical mechanisms underlying olfactory receptor neuron dynamics. Nature Neuroscience. 2011;14:208-216.

    Not in our library10.1038/nn.2725

  47. 47.

    Nern A, Pfeiffer BD, Rubin GM. Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system. Proceedings of the National Academy of Sciences of the United States of America. 2015;112:E2967-E2976.

    Not in our library10.1073/pnas.1506763112

  48. 48.

    Ohyama T, Schneider-Mizell CM, Fetter RD, Aleman JV, Franconville R, Rivera-Alba M, Mensh BD, Branson KM, Simpson JH, Truman JW, Cardona A, Zlatic M. A multilevel multimodal circuit enhances action selection in Drosophila. Nature. 2015;520:633-639.

    Not in our library10.1038/nature14297

  49. 49.

    Okada R, Awasaki T, Ito K. Gamma-aminobutyric acid (GABA)-mediated neural connections in the Drosophila antennal lobe. The Journal of Comparative Neurology. 2009;514:74-91.

    Not in our library10.1002/cne.21971

  50. 50.

    Oland LA, Biebelhausen JP, Tolbert LP. Glial investment of the adult and developing antennal lobe of Drosophila. The Journal of Comparative Neurology. 2008;509:526-550.

    Not in our library10.1002/cne.21762

  51. 51.

    Olsen SR, Bhandawat V, Wilson RI. Divisive normalization in olfactory population codes. Neuron. 2010;66:287-299.

    Not in our library10.1016/j.neuron.2010.04.009

  52. 52.

    Olsen SR, Wilson RI. Lateral presynaptic inhibition mediates gain control in an olfactory circuit. Nature. 2008;452:956-960.

    Not in our library10.1038/nature06864

  53. 53.

    Otsu N. A threshold selection method from gray-level histograms. Automatica. 1975;11:23-27.

    Not in our library10.1109/tsmc.1979.4310076

  54. 54.

    Prieto-Godino LL, Diegelmann S, Bate M. Embryonic origin of olfactory circuitry in Drosophila: contact and activity-mediated interactions pattern connectivity in the antennal lobe. PLoS Biology. 2012;10:e14859.

    Not in our library10.1371/journal.pbio.1001400

  55. 55.

    Python F, Stocker RF. Adult-like complexity of the larval antennal lobe of D. melanogaster despite markedly low numbers of odorant receptor neurons. The Journal of Comparative Neurology. 2002;445:374-387.

    Not in our library10.1002/cne.10188

  56. 56.

    Rall W, Shepherd GM, Reese TS, Brightman MW. Dendrodendritic synaptic pathway for inhibition in the olfactory bulb. Experimental Neurology. 1966;14:44-56.

    Not in our library10.1016/0014-4886(66)90023-9

  57. 57.

    Ramaekers A, Magnenat E, Marin EC, Gendre N, Jefferis GS, Luo L, Stocker RF. Glomerular maps without cellular redundancy at successive levels of the Drosophila larval olfactory circuit. Current Biology. 2005;15:982-992.

    Not in our library10.1016/j.cub.2005.04.032

  58. 58.

    Ressler KJ, Sullivan SL, Buck LB. Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell. 1994;79:1245-1255.

    Not in our library10.1016/0092-8674(94)90015-9

  59. 59.

    Roy B, Singh AP, Shetty C, Chaudhary V, North A, Landgraf M, Vijayraghavan K, Rodrigues V. Metamorphosis of an identified serotonergic neuron in the Drosophila olfactory system. Neural Development. 2007;2:20.

    Not in our library10.1186/1749-8104-2-20

  60. 60.

    Rybak J, Talarico G, Ruiz S, Arnold C, Cantera R, Hansson BS. Synaptic circuitry of identified neurons in the antennal lobe of Drosophila melanogaster. Journal of Comparative Neurology. 2016;524:1920-1956.

    Not in our library10.1002/cne.23966

  61. 61.

    Saalfeld S, Cardona A, Hartenstein V, Tomancak P. CATMAID: collaborative annotation toolkit for massive amounts of image data. Bioinformatics. 2009;25:1984-1986.

    Not in our library10.1093/bioinformatics/btp266

  62. 62.

    Sachse S, Galizia CG. Role of inhibition for temporal and spatial odor representation in olfactory output neurons: a calcium imaging study. Journal of Neurophysiology. 2002;87:1106-1117.

    Not in our library10.1152/jn.00325.2001

  63. 63.

    Satou M, Hara TJ. Synaptic organization of the olfactory bulb and its central projection. Fish Chemoreception, Volume 6 of Fish & Fisheries Series. 1992.

    Not in our library

  64. 64.
  65. 65.
  66. 66.

    Selcho M, Pauls D, El Jundi B, Stocker RF, Thum AS. The role of octopamine and tyramine in Drosophila larval locomotion. The Journal of Comparative Neurology. 2012;520:3764-3785.

    Not in our library10.1002/cne.23152

  67. 67.

    Selcho M, Pauls D, Huser A, Stocker RF, Thum AS. Characterization of the octopaminergic and tyraminergic neurons in the central brain of Drosophila larvae. The Journal of Comparative Neurology. 2014;522:3485-3500.

    Not in our library10.1002/cne.23616

  68. 68.

    Sosulski DL, Bloom ML, Cutforth T, Axel R, Datta SR. Distinct representations of olfactory information in different cortical centres. Nature. 2011;472:213-216.

    Not in our library10.1038/nature09868

  69. 69.

    Stocker RF, Lienhard MC, Borst A, Fischbach KF. Neuronal architecture of the antennal lobe in Drosophila melanogaster. Cell and Tissue Research. 1990;262:9-34.

    Not in our library10.1007/bf00327741

  70. 70.

    Su CY, Menuz K, Carlson JR. Olfactory perception: receptors, cells, and circuits. Cell. 2009;139:45-59.

    Not in our library10.1016/j.cell.2009.09.015

  71. 71.

    Thum AS, Leisibach B, Gendre N, Selcho M, Stocker RF. Diversity, variability, and suboesophageal connectivity of antennal lobe neurons in D. melanogaster larvae. Journal of Comparative Neurology. 2011;519:3415-3432.

    Not in our library10.1002/cne.22713

  72. 72.

    Vogelstein JT, Park Y, Ohyama T, Kerr RA, Truman JW, Priebe CE, Zlatic M. Discovery of brainwide neural-behavioral maps via multiscale unsupervised structure learning. Science. 2014;344:386-392.

    Not in our library10.1126/science.1250298

  73. 73.

    Vosshall LB, Stocker RF. Molecular architecture of smell and taste in Drosophila. Annual Review of Neuroscience. 2007;30:505-533.

    Not in our library10.1146/annurev.neuro.30.051606.094306

  74. 74.

    Vosshall LB, Wong AM, Axel R. An olfactory sensory map in the fly brain. Cell. 2000;102:147-159.

    Not in our library10.1016/s0092-8674(00)00021-0

  75. 75.

    Wang F, Nemes A, Mendelsohn M, Axel R. Odorant receptors govern the formation of a precise topographic map. Cell. 1998;93:47-60.

    Not in our library10.1016/s0092-8674(00)81145-9

  76. 76.

    Wilson RI, Laurent G. Role of GABAergic inhibition in shaping odor-evoked spatiotemporal patterns in the Drosophila antennal lobe. Journal of Neuroscience. 2005;25:9069-9079.

    Not in our library10.1523/jneurosci.2070-05.2005

  77. 77.

    Wong AM, Wang JW, Axel R. Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell. 2002;109:229-241.

    Not in our library10.1016/s0092-8674(02)00707-9

  78. 78.

    Yaksi E, Wilson RI. Electrical coupling between olfactory glomeruli. Neuron. 2010;67:1034-1047.

    Not in our library10.1016/j.neuron.2010.08.041

  79. 79.

    Zhu P, Frank T, Friedrich RW. Equalization of odor representations by a network of electrically coupled inhibitory interneurons. Nature Neuroscience. 2013;16:1678-1686.

    Not in our library10.1038/nn.3528

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