期刊
NEUROPSYCHOPHARMACOLOGY
卷 41, 期 5, 页码 1404-1415出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2015.293
关键词
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资金
- National Institute of Mental Health [R01MH61887, U19MH82441, U01MH105892, R21 MH079145]
- National Institute of Alcohol Abuse and Alcoholism [AA11034, AA07574, AA07611]
- National Institue on Drug Abuse (NIDA) [DA030359, DA015446]
- National Institute of Child Health and Human Development [P30 HD03110]
- NIDA Postdoctoral Training Program at Mount Sinai [DA007135]
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.
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