title: Four Individually Identified Paired Dopamine Neurons Signal Reward in Larval Drosophila.
abstract: Dopaminergic neurons serve multiple functions, including reinforcement processing during associative learning [1-12]. It is thus warranted to understand which dopaminergic neurons mediate which function. We study larval Drosophila, in which only approximately 120 of a total of 10,000 neurons are dopaminergic, as judged by the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis [5, 13]. Dopaminergic neurons mediating reinforcement in insect olfactory learning target the mushroom bodies, a higher-order "cortical" brain region [1-5, 11, 12, 14, 15]. We discover four previously undescribed paired neurons, the primary protocerebral anterior medial (pPAM) neurons. These neurons are TH positive and subdivide the medial lobe of the mushroom body into four distinct subunits. These pPAM neurons are acutely necessary for odor-sugar reward learning and require intact TH function in this process. However, they are dispensable for aversive learning and innate behavior toward the odors and sugars employed. Optogenetical activation of pPAM neurons is sufficient as a reward. Thus, the pPAM neurons convey a likely dopaminergic reward signal. In contrast, DL1 cluster neurons convey a corresponding punishment signal [5], suggesting a cellular division of labor to convey dopaminergic reward and punishment signals. On the level of individually identified neurons, this uncovers an organizational principle shared with adult Drosophila and mammals [1-4, 7, 9, 10] (but see [6]). The numerical simplicity and connectomic tractability of the larval nervous system [16-19] now offers a prospect for studying circuit principles of dopamine function at unprecedented resolution.
authors.affiliation: Department of Biology, University of Fribourg, 1600 Fribourg, Switzerland; Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Rohwedder
authors.affiliation: Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
authors.forename: Nana L
authors.initials: NL
authors.lastname: Wenz
authors.affiliation: Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Stehle
authors.affiliation: Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
authors.forename: Annina
authors.initials: A
authors.lastname: Huser
authors.affiliation: Graduate School of Life Sciences, Tohoku University, Katahira 2-1-1, 980-8577 Sendai, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamagata
authors.affiliation: Janelia Research Campus, Ashburn, VA 20147, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Zlatic
authors.affiliation: Janelia Research Campus, Ashburn, VA 20147, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Truman
authors.affiliation: Graduate School of Life Sciences, Tohoku University, Katahira 2-1-1, 980-8577 Sendai, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Tanimoto
authors.affiliation: Abteilung Genetik von Lernen und Gedächtnis, Leibniz Institut für Neurobiologie (LIN), 39118 Magdeburg, Germany. Electronic address: timo.saumweber@lin-magdeburg.de.
authors.forename: Timo
authors.initials: T
authors.lastname: Saumweber
authors.affiliation: Abteilung Genetik von Lernen und Gedächtnis, Leibniz Institut für Neurobiologie (LIN), 39118 Magdeburg, Germany; Otto von Guericke Universität Magdeburg, Institut für Biologie, Verhaltensgenetik, Universitätsplatz 2, 39106 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany. Electronic address: bertram.gerber@lin-magdeburg.de.
authors.forename: Bertram
authors.initials: B
authors.lastname: Gerber
authors.affiliation: Department of Biology, University of Fribourg, 1600 Fribourg, Switzerland; Department of Biology, University of Konstanz, 78464 Konstanz, Germany; Zukunftskolleg, University of Konstanz, 78464 Konstanz, Germany. Electronic address: andreas.thum@uni-konstanz.de.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Thum
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology; D004330:Drosophila / Q000254:growth & development / Q000502:physiology*; D007814:Larva / Q000502:physiology; D024521:Mushroom Bodies / Q000502:physiology*; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase
keywords: Drosophila larva; dopamine; learning and memory; mushroom body; olfaction; reward; taste