title: Suppression of Dopamine Neurons Mediates Reward.
abstract: Massive activation of dopamine neurons is critical for natural reward and drug abuse. In contrast, the significance of their spontaneous activity remains elusive. In Drosophila melanogaster, depolarization of the protocerebral anterior medial (PAM) cluster dopamine neurons en masse signals reward to the mushroom body (MB) and drives appetitive memory. Focusing on the functional heterogeneity of PAM cluster neurons, we identified that a single class of PAM neurons, PAM-γ3, mediates sugar reward by suppressing their own activity. PAM-γ3 is selectively required for appetitive olfactory learning, while activation of these neurons in turn induces aversive memory. Ongoing activity of PAM-γ3 gets suppressed upon sugar ingestion. Strikingly, transient inactivation of basal PAM-γ3 activity can substitute for reward and induces appetitive memory. Furthermore, we identified the satiety-signaling neuropeptide Allatostatin A (AstA) as a key mediator that conveys inhibitory input onto PAM-γ3. Our results suggest the significance of basal dopamine release in reward signaling and reveal a circuit mechanism for negative regulation.
authors.affiliation: Tohoku University Graduate School of Life Sciences, Sendai, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamagata
authors.affiliation: The University of Tokyo, Institute of Molecular and Cellular Biosciences, Tokyo, Japan.
authors.forename: Makoto
authors.identifier: http://orcid.org/0000-0002-0136-5891
authors.initials: M
authors.lastname: Hiroi
authors.affiliation: National Institute of Genetics, Mishima, Japan.
authors.forename: Shu
authors.identifier: http://orcid.org/0000-0002-4625-8379
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Tohoku University Graduate School of Life Sciences, Sendai, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Abe
authors.affiliation: Tohoku University Graduate School of Life Sciences, Sendai, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Tanimoto
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D024521:Mushroom Bodies / Q000378:metabolism; D010455:Peptides / Q000502:physiology; D012201:Reward; D015398:Signal Transduction
chemical_list: D010455:Peptides; C000591159:allostatine