The wiring diagram of a glomerular olfactory system

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.

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

[2]  Leslie B. Vosshall,et al.  Chemotaxis Behavior Mediated by Single Larval Olfactory Neurons in Drosophila , 2005, Current Biology.

[3]  Nathan W. Gouwens,et al.  Signal Propagation in Drosophila Central Neurons , 2009, The Journal of Neuroscience.

[4]  Dennis Pauls,et al.  The Role of octopamine and tyramine in Drosophila larval locomotion , 2012, The Journal of comparative neurology.

[5]  R. Axel,et al.  Odorant Receptors Govern the Formation of a Precise Topographic Map , 1998, Cell.

[6]  Shawn R. Olsen,et al.  Divisive Normalization in Olfactory Population Codes , 2010, Neuron.

[7]  B. Nadler,et al.  Global Features of Neural Activity in the Olfactory System Form a Parallel Code That Predicts Olfactory Behavior and Perception , 2010, The Journal of Neuroscience.

[8]  R. Friedrich,et al.  Equalization of odor representations by a network of electrically coupled inhibitory interneurons , 2013, Nature Neuroscience.

[9]  Andrew M Dacks,et al.  Serotonin Modulates Olfactory Processing in the Antennal Lobe of Drosophila , 2009, Journal of neurogenetics.

[10]  Katherine I. Nagel,et al.  Biophysical mechanisms underlying olfactory receptor neuron dynamics , 2010, Nature Neuroscience.

[11]  Matthieu Louis,et al.  A circuit supporting concentration-invariant odor perception in Drosophila , 2009, Journal of biology.

[12]  Kei Ito,et al.  Gamma‐aminobutyric acid (GABA)‐mediated neural connections in the Drosophila antennal lobe , 2009, The Journal of comparative neurology.

[13]  Hong Lei,et al.  Local inhibition modulates odor-evoked synchronization of glomerulus-specific output neurons , 2002, Nature Neuroscience.

[14]  Lucia L. Prieto-Godino,et al.  Embryonic Origin of Olfactory Circuitry in Drosophila: Contact and Activity-Mediated Interactions Pattern Connectivity in the Antennal Lobe , 2012, PLoS biology.

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

[16]  Xiaojing J. Gao,et al.  Extremely Sparse Olfactory Inputs Are Sufficient to Mediate Innate Aversion in Drosophila , 2015, PloS one.

[17]  Synaptic connection between olfactory receptor cells and uniglomerular projection neurons in the antennal lobe of the American cockroach, Periplaneta americana , 1996, The Journal of comparative neurology.

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

[19]  V. Hartenstein,et al.  Neuroblast lineage-specific origin of the neurons of the Drosophila larval olfactory system. , 2013, Developmental biology.

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

[21]  André Fiala,et al.  Behavioral Neuroscience , 2022 .

[22]  G. Laurent,et al.  Role of GABAergic Inhibition in Shaping Odor-Evoked Spatiotemporal Patterns in the Drosophila Antennal Lobe , 2005, The Journal of Neuroscience.

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

[24]  Matthias Landgraf,et al.  Metamorphosis of an identified serotonergic neuron in the Drosophila olfactory system , 2007, Neural Development.

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

[26]  R. Stocker,et al.  Adult‐like complexity of the larval antennal lobe of D. melanogaster despite markedly low numbers of odorant receptor neurons , 2002, The Journal of comparative neurology.

[27]  L. Tolbert,et al.  Glial investment of the adult and developing antennal lobe of Drosophila , 2008, The Journal of comparative neurology.

[28]  David Harel,et al.  A metric for odorant comparison , 2008, Nature Methods.

[29]  R. Kerr,et al.  Discovery of Brainwide Neural-Behavioral Maps via Multiscale Unsupervised Structure Learning , 2014, Science.

[30]  John R. Carlson,et al.  Translation of Sensory Input into Behavioral Output via an Olfactory System , 2008, Neuron.

[31]  Shawn R. Olsen,et al.  Lateral presynaptic inhibition mediates gain control in an olfactory circuit , 2008, Nature.

[32]  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.

[33]  Andreas S. Thum,et al.  Characterization of the octopaminergic and tyraminergic neurons in the central brain of Drosophila larvae , 2014, The Journal of comparative neurology.

[34]  Mason Klein,et al.  Reverse-correlation analysis of navigation dynamics in Drosophila larva using optogenetics , 2015, bioRxiv.

[35]  Bertram Gerber,et al.  The Drosophila larva as a model for studying chemosensation and chemosensory learning: a review. , 2007, Chemical senses.

[36]  Katherine I. Nagel,et al.  Synaptic and circuit mechanisms promoting broadband transmission of olfactory stimulus dynamics , 2014, Nature Neuroscience.

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

[38]  John R. Carlson,et al.  Functional diversity among sensory receptors in a Drosophila olfactory circuit , 2013, Proceedings of the National Academy of Sciences.

[39]  G M Shepherd,et al.  Dendrodendritic synaptic pathway for inhibition in the olfactory bulb. , 1966, Experimental neurology.

[40]  L. Abbott,et al.  Generating sparse and selective third-order responses in the olfactory system of the fly , 2010, Proceedings of the National Academy of Sciences.

[41]  Gregory S.X.E. Jefferis,et al.  Glomerular Maps without Cellular Redundancy at Successive Levels of the Drosophila Larval Olfactory Circuit , 2005, Current Biology.

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

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

[44]  Andreas S. Thum,et al.  Diversity, variability, and suboesophageal connectivity of antennal lobe neurons in D. melanogaster larvae , 2011, The Journal of comparative neurology.

[45]  N. Otsu.  A threshold selection method from gray level histograms , 1979 .

[46]  Yoshihiro Yoshihara,et al.  Mitral and tufted cells differ in the decoding manner of odor maps in the rat olfactory bulb. , 2004, Journal of neurophysiology.

[47]  L. Luo,et al.  Diversity and Wiring Variability of Olfactory Local Interneurons in the Drosophila Antennal Lobe , 2010, Nature Neuroscience.

[48]  Richard Axel,et al.  An Olfactory Sensory Map in the Fly Brain , 2000, Cell.

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

[50]  Gerald M Rubin,et al.  A resource for manipulating gene expression and analyzing cis-regulatory modules in the Drosophila CNS. , 2012, Cell reports.

[51]  L. Vosshall,et al.  Bilateral olfactory sensory input enhances chemotaxis behavior , 2008, Nature Neuroscience.

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

[53]  M. Carandini.  From circuits to behavior: a bridge too far? , 2012, Nature Neuroscience.

[54]  Stephan Saalfeld,et al.  CATMAID: collaborative annotation toolkit for massive amounts of image data , 2009, Bioinform..

[55]  U. Alon.  Network motifs: theory and experimental approaches , 2007, Nature Reviews Genetics.

[56]  Aaron DiAntonio,et al.  Increased Expression of the Drosophila Vesicular Glutamate Transporter Leads to Excess Glutamate Release and a Compensatory Decrease in Quantal Content , 2004, The Journal of Neuroscience.

[57]  B. Smith,et al.  A computational model of the response of honey bee antennal lobe circuitry to odor mixtures: overshadowing, blocking and unblocking can arise from lateral inhibition , 1997, Behavioural Brain Research.

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

[59]  B. Gerber,et al.  Cellular site and molecular mode of synapsin action in associative learning. , 2011, Learning & memory.

[60]  Linda B. Buck,et al.  Information coding in the olfactory system: Evidence for a stereotyped and highly organized epitope map in the olfactory bulb , 1994, Cell.

[61]  J. Carlson,et al.  Similar Odorants Elicit Different Behavioral and Physiological Responses, Some Supersustained , 2011, The Journal of Neuroscience.

[62]  S. Sachse,et al.  Role of inhibition for temporal and spatial odor representation in olfactory output neurons: a calcium imaging study. , 2002, Journal of neurophysiology.

[63]  Natalie M Bernat,et al.  Computations underlying Drosophila photo-taxis, odor-taxis, and multi-sensory integration , 2015, eLife.

[64]  M. Cobb.  What and how do maggots smell? , 1999 .

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

[66]  Shilpy Sharma,et al.  An Optimized Method for Histological Detection of Dopaminergic Neurons in Drosophila melanogaster , 2008, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

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

[68]  M. Heisenberg,et al.  Neurogenetics and Behaviour in Insects , 1984 .

[69]  Parvez Ahammad,et al.  Dynamical feature extraction at the sensory periphery guides chemotaxis , 2015, eLife.

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

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

[72]  Aravinthan D. T. Samuel,et al.  Controlling airborne cues to study small animal navigation , 2012, Nature Methods.

[73]  B. Strowbridge,et al.  Multiple Modes of Synaptic Excitation of Olfactory Bulb Granule Cells , 2007, The Journal of Neuroscience.

[74]  A. Gomez-Marin,et al.  Active sampling and decision making in Drosophila chemotaxis , 2011, Nature communications.

[75]  R. Friedrich,et al.  Combinatorial and Chemotopic Odorant Coding in the Zebrafish Olfactory Bulb Visualized by Optical Imaging , 1997, Neuron.

[76]  R. Stocker,et al.  Localized olfactory representation in mushroom bodies of Drosophila larvae , 2009, Proceedings of the National Academy of Sciences.

[77]  Shawn R. Olsen,et al.  Sensory processing in the Drosophila antennal lobe increases reliability and separability of ensemble odor representations , 2007, Nature Neuroscience.

[78]  M. Satou.  Synaptic organization of the olfactory bulb and its central projection , 1992 .

[79]  Omotara Ogundeyi,et al.  A GAL4 driver resource for developmental and behavioral studies on the larval CNS of Drosophila. , 2014, Cell reports.