Journal article
Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons
Neuropsychopharmacology (New York, N.Y.), Vol.41(5), pp.1404-1415
04/2016
DOI: 10.1038/npp.2015.293
PMCID: PMC4793125
PMID: 26383016
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.
Details
- Title: Subtitle
- Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons
- Creators
- Daniel J Urban - Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USAHu Zhu - Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USACatherine A Marcinkiewcz - Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USAMichael Michaelides - Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USAHidehiro Oshibuchi - Department of Psychiatry, University of California, San Francisco, CA, USADarren Rhea - Department of Psychiatry, University of California, San Francisco, CA, USADipendra K Aryal - Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Duke University Medical Center, Durham, NC, USAMartilias S Farrell - Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USAEmily Lowery-Gionta - Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USAReid H J Olsen - Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USAWilliam C Wetsel - Departments of Psychiatry and Behavioral Sciences, Cell Biology, and Neurobiology, Duke University Medical Center, Durham, NC, USAThomas L Kash - Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC, USAYasmin L Hurd - Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USALaurence H Tecott - Department of Psychiatry, University of California, San Francisco, CA, USABryan L Roth - Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program, Chapel Hill, NC, USA
- Resource Type
- Journal article
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), Vol.41(5), pp.1404-1415
- Publisher
- England
- DOI
- 10.1038/npp.2015.293
- PMID
- 26383016
- PMCID
- PMC4793125
- ISSN
- 0893-133X
- eISSN
- 1740-634X
- Grant note
- R01 MH061887 / NIMH NIH HHS R21 MH079145 / NIMH NIH HHS U19 MH082441 / NIMH NIH HHS P30 DK063720 / NIDDK NIH HHS AA11034 / NIAAA NIH HHS R01MH61887 / NIMH NIH HHS U54 HD079124 / NICHD NIH HHS DA030359 / NIDA NIH HHS DA015446 / NIDA NIH HHS U01 MH105892 / NIMH NIH HHS AA07574 / NIAAA NIH HHS U01MH105892 / NIMH NIH HHS T32 GM007040 / NIGMS NIH HHS U19MH82441 / NIMH NIH HHS DA007135 / NIDA NIH HHS AA07611 / NIAAA NIH HHS P30 HD03110 / NICHD NIH HHS
- Language
- English
- Date published
- 04/2016
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040337902771
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