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

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...

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Autores principales: Grandjean, Joanes, Corcoba, Alberto, Kahn, Martin C., Upton, A. Louise, Deneris, Evan S., Seifritz, Erich, Helmchen, Fritjof, Mann, Edward O., Rudin, Markus, Saab, Bechara J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341094/
https://www.ncbi.nlm.nih.gov/pubmed/30664643
http://dx.doi.org/10.1038/s41467-018-08256-w
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author Grandjean, Joanes
Corcoba, Alberto
Kahn, Martin C.
Upton, A. Louise
Deneris, Evan S.
Seifritz, Erich
Helmchen, Fritjof
Mann, Edward O.
Rudin, Markus
Saab, Bechara J.
author_facet Grandjean, Joanes
Corcoba, Alberto
Kahn, Martin C.
Upton, A. Louise
Deneris, Evan S.
Seifritz, Erich
Helmchen, Fritjof
Mann, Edward O.
Rudin, Markus
Saab, Bechara J.
author_sort Grandjean, Joanes
collection PubMed
description 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.
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spelling pubmed-63410942019-01-23 A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine Grandjean, Joanes Corcoba, Alberto Kahn, Martin C. Upton, A. Louise Deneris, Evan S. Seifritz, Erich Helmchen, Fritjof Mann, Edward O. Rudin, Markus Saab, Bechara J. Nat Commun Article 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. Nature Publishing Group UK 2019-01-21 /pmc/articles/PMC6341094/ /pubmed/30664643 http://dx.doi.org/10.1038/s41467-018-08256-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Grandjean, Joanes
Corcoba, Alberto
Kahn, Martin C.
Upton, A. Louise
Deneris, Evan S.
Seifritz, Erich
Helmchen, Fritjof
Mann, Edward O.
Rudin, Markus
Saab, Bechara J.
A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
title A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
title_full A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
title_fullStr A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
title_full_unstemmed A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
title_short A brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
title_sort brain-wide functional map of the serotonergic responses to acute stress and fluoxetine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341094/
https://www.ncbi.nlm.nih.gov/pubmed/30664643
http://dx.doi.org/10.1038/s41467-018-08256-w
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