title: Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons.
abstract: Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes-hours) and long period of time (days-weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons.
authors.affiliation: Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Urban
authors.affiliation: Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Marcinkiewcz
authors.affiliation: Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Michaelides
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oshibuchi
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Rhea
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Dipendra K
authors.initials: DK
authors.lastname: Aryal
authors.affiliation: Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USA.
authors.forename: Martilias S
authors.initials: MS
authors.lastname: Farrell
authors.affiliation: Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Lowery-Gionta
authors.affiliation: Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USA.
authors.forename: Reid H J
authors.initials: RH
authors.lastname: Olsen
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.affiliation: Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
authors.affiliation: Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yasmin L
authors.initials: YL
authors.lastname: Hurd
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Tecott
authors.affiliation: Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002940:Circadian Rhythm; D003863:Depression / Q000503:physiopathology*; D015198:Designer Drugs / Q000008:administration & dosage; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
chemical_list: D015198:Designer Drugs