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

Joanes Grandjean (), Alberto Corcoba, Martin C. Kahn, A. Louise Upton, Evan S. Deneris, Erich Seifritz, Fritjof Helmchen, Isabelle M. Mansuy, Edward O. Mann, Markus Rudin and Bechara J. Saab ()
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Joanes Grandjean: Agency for Science Technology and Research
Alberto Corcoba: University of Lausanne
Martin C. Kahn: University of Zurich Hospital for Psychiatry
A. Louise Upton: University of Oxford
Evan S. Deneris: Case Western Reserve University School of Medicine
Erich Seifritz: Neuroscience Center Zurich
Fritjof Helmchen: Neuroscience Center Zurich
Isabelle M. Mansuy: Department of Health Science and Technology of ETH Zürich
Edward O. Mann: University of Oxford
Markus Rudin: Neuroscience Center Zurich
Bechara J. Saab: Neuroscience Center Zurich

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08256-w

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