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Whole-Brain opto-fMRI Map of Mouse VTA Dopaminergic Activation Reflects Structural Projections with Small but Significant Deviations

View ORCID ProfileHorea-Ioan Ioanas, View ORCID ProfileBechara John Saab, View ORCID ProfileMarkus Rudin
doi: https://doi.org/10.1101/2020.04.03.023648
Horea-Ioan Ioanas
1Institute for Biomedical Engineering, ETH and University of Zurich
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  • For correspondence: horea@mit.edu
Bechara John Saab
2Preclinical Laboratory for Translational Research into Affective Disorders, DPPP, Psychiatric Hospital, University of Zurich
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Markus Rudin
1Institute for Biomedical Engineering, ETH and University of Zurich
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Abstract

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 evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signalling 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • formatting and background section improvement. Corrected source data link.

  • https://zenodo.org/record/3575149/files/opfvta_bidsdata-2.0.tar.xz

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 24, 2021.
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Whole-Brain opto-fMRI Map of Mouse VTA Dopaminergic Activation Reflects Structural Projections with Small but Significant Deviations
Horea-Ioan Ioanas, Bechara John Saab, Markus Rudin
bioRxiv 2020.04.03.023648; doi: https://doi.org/10.1101/2020.04.03.023648
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Whole-Brain opto-fMRI Map of Mouse VTA Dopaminergic Activation Reflects Structural Projections with Small but Significant Deviations
Horea-Ioan Ioanas, Bechara John Saab, Markus Rudin
bioRxiv 2020.04.03.023648; doi: https://doi.org/10.1101/2020.04.03.023648

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