A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine

Nat Commun. 2019 Jan 21;10(1):350. doi: 10.1038/s41467-018-08256-w.

Abstract

Central serotonin (5-HT) orchestrates myriad cognitive processes and lies at the core of many stress-related psychiatric illnesses. However, the basic relationship between its brain-wide axonal projections and functional dynamics is not known. Here we combine optogenetics and fMRI to produce a brain-wide 5-HT evoked functional map. We find that DRN photostimulation leads to an increase in the hemodynamic response in the DRN itself, while projection areas predominately exhibit a reduction of cerebral blood volume mirrored by suppression of cortical delta oscillations. We find that the regional distribution of post-synaptically expressed 5-HT receptors better correlates with DRN 5-HT functional connectivity than anatomical projections. Our work suggests that neuroarchitecture is not the primary determinant of function for the DRN 5-HT. With respect to two 5-HT elevating stimuli, we find that acute stress leads to circuit-wide blunting of the DRN output, while the SSRI fluoxetine noticeably enhances DRN functional connectivity. These data provide fundamental insight into the brain-wide functional dynamics of the 5-HT projection system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping / methods
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Cerebrovascular Circulation / drug effects
  • Dorsal Raphe Nucleus / diagnostic imaging*
  • Dorsal Raphe Nucleus / drug effects
  • Dorsal Raphe Nucleus / metabolism
  • Dorsal Raphe Nucleus / physiopathology
  • Evoked Potentials, Visual / drug effects
  • Female
  • Fluoxetine / pharmacology*
  • Immobilization
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Transgenic
  • Optogenetics
  • Photic Stimulation
  • Receptors, Serotonin / metabolism*
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / metabolism
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology

Substances

  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin