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

Neuropsychopharmacology. 2016 Apr;41(5):1404-15. doi: 10.1038/npp.2015.293. Epub 2015 Sep 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / physiopathology*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiology
  • Circadian Rhythm
  • Depression / physiopathology*
  • Designer Drugs / administration & dosage
  • Dorsal Raphe Nucleus / drug effects
  • Dorsal Raphe Nucleus / metabolism
  • Dorsal Raphe Nucleus / physiology*
  • Male
  • Mice
  • Mice, Transgenic
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / metabolism
  • Serotonergic Neurons / physiology*
  • Time Factors

Substances

  • Designer Drugs