Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Daniel J Urban, Hu Zhu, Catherine A Marcinkiewcz, Michael Michaelides, Hidehiro Oshibuchi, Darren Rhea, Dipendra K Aryal, Martilias S Farrell, Emily Lowery-Gionta, Reid H J Olsen, William C Wetsel, Thomas L Kash (+3 others)
2015 Neuropsychopharmacology  
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
more » ... ust 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.
doi:10.1038/npp.2015.293 pmid:26383016 pmcid:PMC4793125 fatcat:4fhcrsav5bhovlg7yztqfn5hpi