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      Functional architecture of reward learning in mushroom body extrinsic neurons of larval Drosophila

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          Abstract

          The brain adaptively integrates present sensory input, past experience, and options for future action. The insect mushroom body exemplifies how a central brain structure brings about such integration. Here we use a combination of systematic single-cell labeling, connectomics, transgenic silencing, and activation experiments to study the mushroom body at single-cell resolution, focusing on the behavioral architecture of its input and output neurons (MBINs and MBONs), and of the mushroom body intrinsic APL neuron. Our results reveal the identity and morphology of almost all of these 44 neurons in stage 3 Drosophila larvae. Upon an initial screen, functional analyses focusing on the mushroom body medial lobe uncover sparse and specific functions of its dopaminergic MBINs, its MBONs, and of the GABAergic APL neuron across three behavioral tasks, namely odor preference, taste preference, and associative learning between odor and taste. Our results thus provide a cellular-resolution study case of how brains organize behavior.

          Abstract

          The mushroom body of Drosophila integrates sensory information with past experience to guide behaviour. Here, the authors provide an atlas of the input and output neurons of the stage 3 larval mushroom body at the single-cell level, and analyse their function in learned and innate behaviours.

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          Most cited references66

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          Mushroom body memoir: from maps to models.

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            Molecular architecture of smell and taste in Drosophila.

            The chemical senses-smell and taste-allow animals to evaluate and distinguish valuable food resources from dangerous substances in the environment. The central mechanisms by which the brain recognizes and discriminates attractive and repulsive odorants and tastants, and makes behavioral decisions accordingly, are not well understood in any organism. Recent molecular and neuroanatomical advances in Drosophila have produced a nearly complete picture of the peripheral neuroanatomy and function of smell and taste in this insect. Neurophysiological experiments have begun to provide insight into the mechanisms by which these animals process chemosensory cues. Given the considerable anatomical and functional homology in smell and taste pathways in all higher animals, experimental approaches in Drosophila will likely provide broad insights into the problem of sensory coding. Here we provide a critical review of the recent literature in this field and comment on likely future directions.
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              Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons.

              T Kitamoto (2001)
              Behavior is a manifestation of temporally and spatially defined neuronal activities. To understand how behavior is controlled by the nervous system, it is important to identify the neuronal substrates responsible for these activities, and to elucidate how they are integrated into a functional circuit. I introduce a novel and general method to conditionally perturb anatomically defined neurons in intact Drosophila. In this method, a temperature-sensitive allele of shibire (shi(ts1)) is overexpressed in neuronal subsets using the GAL4/UAS system. Because the shi gene product is essential for synaptic vesicle recycling, and shi(ts1) is semidominant, a simple temperature shift should lead to fast and reversible effects on synaptic transmission of shi(ts1) expressing neurons. When shi(ts1) expression was directed to cholinergic neurons, adult flies showed a dramatic response to the restrictive temperature, becoming motionless within 2 min at 30 degrees C. This temperature-induced paralysis was reversible. After being shifted back to the permissive temperature, they readily regained their activity and started to walk in 1 min. When shi(ts1) was expressed in photoreceptor cells, adults and larvae exhibited temperature-dependent blindness. These observations show that the GAL4/UAS system can be used to express shi(ts1) in a specific subset of neurons to cause temperature-dependent changes in behavior. Because this method allows perturbation of the neuronal activities rapidly and reversibly in a spatially and temporally restricted manner, it will be useful to study the functional significance of particular neuronal subsets in the behavior of intact animals. Copyright 2001 John Wiley & Sons, Inc.
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                Author and article information

                Contributors
                andreas.thum@uni-leipzig.de
                bertram.gerber@lin-magdeburg.de
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                16 March 2018
                16 March 2018
                2018
                : 9
                : 1104
                Affiliations
                [1 ]ISNI 0000 0001 2109 6265, GRID grid.418723.b, Department of Genetics, , Leibniz Institute for Neurobiology (LIN), ; Brenneckestr. 6, 39118 Magdeburg, Germany
                [2 ]ISNI 0000 0001 0658 7699, GRID grid.9811.1, Institute for Biology, , University of Konstanz, ; Universitätsstraße 10, 78464 Konstanz, Germany
                [3 ]ISNI 0000 0001 2167 1581, GRID grid.413575.1, HHMI Janelia Research Campus, ; Helix Drive 19700, Ashburn, VA 20147 USA
                [4 ]ISNI 0000 0001 2109 6265, GRID grid.418723.b, Special Lab Electron and Laserscanning Microscopy and Combinatorial Neuro Imaging Core Facility, , Leibniz Institute for Neurobiology (LIN), ; Brenneckestr. 6, 39118 Magdeburg, Germany
                [5 ]ISNI 0000000122986657, GRID grid.34477.33, Friday Harbor Laboratories, , University of Washington, ; Friday Harbor, WA 98250 USA
                [6 ]ISNI 0000 0001 0658 7699, GRID grid.9811.1, Zukunftskolleg, , University of Konstanz, ; Universitätsstraße 10, 78464 Konstanz, Germany
                [7 ]ISNI 0000 0001 2230 9752, GRID grid.9647.c, Institute for Biology, , University of Leipzig, ; Talstraße 33, 04103 Leipzig, Germany
                [8 ]ISNI 0000 0001 2109 6265, GRID grid.418723.b, Center for Behavioral Brain Sciences (CBBS), ; Universitätsplatz 2, 39106 Magdeburg, Germany
                [9 ]ISNI 0000 0001 1018 4307, GRID grid.5807.a, Institute for Biology, , Otto von Guericke University Magdeburg, ; Universitätsplatz 2, 39106 Magdeburg, Germany
                Author information
                http://orcid.org/0000-0001-8020-1483
                http://orcid.org/0000-0002-7833-8621
                http://orcid.org/0000-0003-4941-6536
                http://orcid.org/0000-0002-8092-3440
                http://orcid.org/0000-0002-3830-6596
                http://orcid.org/0000-0003-3003-0051
                Article
                3130
                10.1038/s41467-018-03130-1
                5856778
                29549237
                f809c9d4-5d5c-43b3-bf99-3796816c3b2d
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 March 2017
                : 22 January 2018
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