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Unexpected global impact of VTA dopamine neuron activation as measured by opto-fMRI

Molecular Psychiatry volume 22, pages 585–594 (2017)Cite this article

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Abstract

Dopamine neurons in the ventral tegmental area (VTA) are strongly implicated in cognitive and affective processing as well as in psychiatric disorders, including schizophrenia, depression, attention-deficit hyperactivity disorder and substance abuse disorders. In human studies, dopamine-related functions are routinely assessed using functional magnetic resonance imaging (fMRI) measures of blood oxygenation-level-dependent (BOLD) signals during the performance of dopamine-dependent tasks. There is, however, a critical void in our knowledge about whether and how activation of VTA dopamine neurons specifically influences regional or global fMRI signals. Here, we used optogenetics in Th::Cre rats to selectively stimulate VTA dopamine neurons while simultaneously measuring global hemodynamic changes using BOLD and cerebral blood volume-weighted (CBVw) fMRI. Phasic activation of VTA dopamine neurons increased BOLD and CBVw fMRI signals in VTA-innervated limbic regions, including the ventral striatum (nucleus accumbens). Surprisingly, basal ganglia regions that receive sparse or no VTA dopaminergic innervation, including the dorsal striatum and the globus pallidus, were also activated. In fact, the most prominent fMRI signal increase in the forebrain was observed in the dorsal striatum that is not traditionally associated with VTA dopamine neurotransmission. These data establish causation between phasic activation of VTA dopamine neurons and global fMRI signals. They further suggest that mesolimbic and non-limbic basal ganglia dopamine circuits are functionally connected and thus provide a potential novel framework for understanding dopamine-dependent functions and interpreting data obtained from human fMRI studies.

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Acknowledgements

This work was supported by the National Institutes of Health grants R01 (MH048404 and EB003324), R21 (EB018903), Multimodal Neuroimaging Training Fellowship (University of Pittsburgh) and the Institute for Basic Science (IBS-R015-D1).

Author contributions

SL and AJP performed the experiments and analyzed data. All authors designed the experiments. SL, AJP and BM wrote the paper.

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  1. S Lohani and A J Poplawsky: These two authors are co-first authors.

Authors and Affiliations

  1. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    S Lohani & B Moghaddam

  2. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA

    A J Poplawsky & S-G Kim

  3. Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea

    S-G Kim

  4. Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea

    S-G Kim

  5. Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea

    S-G Kim

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  1. S Lohani
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Correspondence to B Moghaddam.

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Lohani, S., Poplawsky, A., Kim, SG. et al. Unexpected global impact of VTA dopamine neuron activation as measured by opto-fMRI. Mol Psychiatry 22, 585–594 (2017). https://doi.org/10.1038/mp.2016.102

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