Rewarding capacity of optogenetically activating a giant GABAergic central-brain interneuron in larval Drosophila

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Larvae of the fruit fly Drosophila melanogaster are a powerful study case for understanding the neural circuits underlying behavior. Indeed, the numerical simplicity of the larval brain has permitted the reconstruction of its synaptic connectome, and genetic tools for manipulating single, identified neurons allow neural circuit function to be investigated with relative ease and precision. We focus on one of the most complex neurons in the brain of the larva (of either sex), the GABAergic anterior paired lateral neuron (APL). Using behavioral and connectomic analyses, optogenetics, Ca 2+ imaging and pharmacology, we study how APL affects associative olfactory memory. We first provide a detailed account of the structure, regional polarity, connectivity, and metamorphic development of APL, and further confirm that optogenetic activation of APL has an inhibiting effect on its main targets, the mushroom body Kenyon cells. All these findings are consistent with the previously identified function of APL in the sparsening of sensory representations. To our surprise, however, we found that optogenetically activating APL can also have a strong rewarding effect. Specifically, APL activation together with odor presentation establishes an odor-specific, appetitive, associative short-term memory, whereas naïve olfactory behavior remains unaffected. An acute, systemic inhibition of dopamine synthesis as well as an ablation of the dopaminergic pPAM neurons impair reward learning through APL activation. Our findings provide a study case of complex circuit function in a numerically simple brain, and suggest a previously unrecognized capacity of central-brain GABAergic neurons to engage in dopaminergic reinforcement. Significance statement The single, identified giant anterior paired lateral (APL) neuron is one of the most complex neurons in the insect brain. It is GABAergic and contributes to the sparsening of neuronal activity in the mushroom body, the memory center of insects. We provide the most detailed account yet of the structure of APL in larval Drosophila as a neurogenetically accessible study case. We further reveal that, contrary to expectations, the experimental activation of APL can exert a rewarding effect, likely via dopaminergic reward pathways. The present study both provides an example of unexpected circuit complexity in a numerically simple brain, and reports an unexpected effect of activity in central-brain GABAergic circuits.

Authors 17

1. Nino Mancini corresponding

   Leibniz Institute for Neurobiology

   Affiliation as printed

   Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

   Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany

2. Juliane Thoener

   Leibniz Institute for Neurobiology

   Affiliation as printed

   Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

   Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany

3. Esmeralda Tafani

   Leibniz Institute for Neurobiology

   Affiliation as printed

   Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

   Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany

4. Dennis Pauls

   Leipzig University

   Affiliation as printed

   Department of Animal Physiology, Institute of Biology, Leipzig University, 04103 Leipzig, Germany

5. Oded Mayseless

   Weizmann Institute of Science

   Affiliation as printed

   Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001 Israel

6. Martin Strauch Aachen Institute of Imaging & Computer Vision

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University, Institute of Imaging and Computer Vision, 52074 Aachen, Germany

   RWTH Aachen University, Institute of Imaging and Computer Vision, 2074 Aachen, Germany

7. Katharina Eichler

   University of Puerto Rico, Medical Sciences Campus

   Affiliation as printed

   Institute of Neurobiology, University of Puerto Rico Medical Science Campus, Old San Juan, Puerto Rico 00901

8. Andrew Scott Champion

   University of Cambridge · Howard Hughes Medical Institute · Janelia Research Campus

   Affiliation as printed

   Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, CB2 3EL, United Kingdom

   Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA

9. Oliver Kobler

   Leibniz Institute for Neurobiology

   Affiliation as printed

   Leibniz Institute for Neurobiology (LIN), Combinatorial Neuroimaging Core Facility (CNI), 39118 Magdeburg, Germany

   Leibniz Institute for Neurobiology (LIN), Combinatorial Neuroimaging Core Facility (CNI), 3118 Magdeburg, Germany

10. Denise Weber

    Leipzig University

    Affiliation as printed

    Department of Genetics, Institute of Biology, Leipzig University, 04103 Leipzig, Germany

    Department of Genetics, Institute of Biology, Leipzig University, 0410 Leipzig, Germany

11. Edanur Sen

    Leibniz Institute for Neurobiology

    Affiliation as printed

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany

12. Aliće Weiglein

    Leibniz Institute for Neurobiology

    Affiliation as printed

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany

13. Volker Hartenstein

    University of California, Los Angeles

    Affiliation as printed

    University of California, Department of Molecular, Cell and Developmental Biology, CA 90095-1606, Los Angeles, USA

14. Andreas S. Thum

    Leipzig University

    Affiliation as printed

    Department of Genetics, Institute of Biology, Leipzig University, 04103 Leipzig, Germany

    Department of Genetics, Institute of Biology, Leipzig University, 0410 Leipzig, Germany

15. Astrid Rohwedder

    Leipzig University

    Affiliation as printed

    Department of Genetics, Institute of Biology, Leipzig University, 04103 Leipzig, Germany

    Department of Genetics, Institute of Biology, Leipzig University, 0410 Leipzig, Germany

16. Michael Schleyer

    Leibniz Institute for Neurobiology

    Affiliation as printed

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany

17. Bertram Gerber corresponding

    Otto-von-Guericke-Universität Magdeburg · Center for Behavioral Brain Sciences · Leibniz Institute for Neurobiology

    Affiliation as printed

    Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany

    Institute for Biology, Otto von Guericke University, 39106 Magdeburg, Germany

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 39118 Magdeburg, Germany

    Leibniz Institute for Neurobiology (LIN), Department Genetics of Learning and Memory, 398 Magdeburg, Germany