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Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations

Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to the evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an...

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Autores principales: Ioanas, Horea-Ioan, Saab, Bechara John, Rudin, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844000/
https://www.ncbi.nlm.nih.gov/pubmed/35165257
http://dx.doi.org/10.1038/s41398-022-01812-5
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author Ioanas, Horea-Ioan
Saab, Bechara John
Rudin, Markus
author_facet Ioanas, Horea-Ioan
Saab, Bechara John
Rudin, Markus
author_sort Ioanas, Horea-Ioan
collection PubMed
description Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to the evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signaling in the mouse brain is crucial for the translational investigation of motivational control as well as of neuronal function phenotypes for diseases and interventions. In this article we use optogenetic stimulation directed at VTA dopaminergic neurons in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present a comprehensive assay producing the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with its structural VTA projections, diverging only in a few key aspects. While the activation map predominantly highlights target areas according to their relative projection densities (e.g., strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail the variability of the assay with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide evidence-based recommendations for assay reuse, publishing both reference results and a reference analysis workflow implementation.
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spelling pubmed-88440002022-03-02 Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations Ioanas, Horea-Ioan Saab, Bechara John Rudin, Markus Transl Psychiatry Article Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to the evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signaling in the mouse brain is crucial for the translational investigation of motivational control as well as of neuronal function phenotypes for diseases and interventions. In this article we use optogenetic stimulation directed at VTA dopaminergic neurons in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present a comprehensive assay producing the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with its structural VTA projections, diverging only in a few key aspects. While the activation map predominantly highlights target areas according to their relative projection densities (e.g., strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail the variability of the assay with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide evidence-based recommendations for assay reuse, publishing both reference results and a reference analysis workflow implementation. Nature Publishing Group UK 2022-02-14 /pmc/articles/PMC8844000/ /pubmed/35165257 http://dx.doi.org/10.1038/s41398-022-01812-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ioanas, Horea-Ioan
Saab, Bechara John
Rudin, Markus
Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
title Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
title_full Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
title_fullStr Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
title_full_unstemmed Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
title_short Whole-brain opto-fMRI map of mouse VTA dopaminergic activation reflects structural projections with small but significant deviations
title_sort whole-brain opto-fmri map of mouse vta dopaminergic activation reflects structural projections with small but significant deviations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844000/
https://www.ncbi.nlm.nih.gov/pubmed/35165257
http://dx.doi.org/10.1038/s41398-022-01812-5
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