title: Serotonergic versus nonserotonergic dorsal raphe projection neurons: differential participation in reward circuitry.
abstract: The dorsal raphe nucleus (DRN) contains the largest group of serotonin-producing neurons in the brain and projects to regions controlling reward. Although pharmacological studies suggest that serotonin inhibits reward seeking, electrical stimulation of the DRN strongly reinforces instrumental behavior. Here, we provide a targeted assessment of the behavioral, anatomical, and electrophysiological contributions of serotonergic and nonserotonergic DRN neurons to reward processes. To explore DRN heterogeneity, we used a simultaneous two-vector knockout/optogenetic stimulation strategy, as well as cre-induced and cre-silenced vectors in several cre-expressing transgenic mouse lines. We found that the DRN is capable of reinforcing behavior primarily via nonserotonergic neurons, for which the main projection target is the ventral tegmental area (VTA). Furthermore, these nonserotonergic projections provide glutamatergic excitation of VTA dopamine neurons and account for a large majority of the DRN-VTA pathway. These findings help to resolve apparent discrepancies between the roles of serotonin versus the DRN in behavioral reinforcement.
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Ross A
authors.initials: RA
authors.lastname: McDevitt
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; Départment de Biologie, Ecole Normale Supérieure, 69007 Lyon, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Tiran-Cappello
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, A.P. 70-253, México D.F. 04510, México.
authors.forename: Israela
authors.initials: I
authors.lastname: Balderas
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Britt
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Rosa A M
authors.initials: RAM
authors.lastname: Marino
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Chung
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Richie
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.affiliation: Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA; Solomon H. Snyder Neuroscience Institute, Johns Hopkins University School of Medicine, Baltimore MD 21205, USA. Electronic address: antonello.bonci@nih.gov.
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000378:metabolism*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D005277:Fenfluramine; D012701:Serotonin; D000661:Amphetamine; D004298:Dopamine