Functional dissection of neural circuitry using a genetic reporter for fMRI
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nihms-1805477.pdf
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Accepted version
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2.92 MB
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Author(s) • • • • • • • • •
Ghosh, Souparno
Li, Nan
Schwalm, Miriam
Bartelle, Benjamin B
Xie, Tianshu
Daher, Jade I
Singh, Urvashi D
Xie, Katherine
DiNapoli, Nicholas
Evans, Nicholas B
Date Issued
2022
Journal
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Citation
Ghosh, Souparno, Li, Nan, Schwalm, Miriam, Bartelle, Benjamin B, Xie, Tianshu et al. 2022. "Functional dissection of neural circuitry using a genetic reporter for fMRI." Nature Neuroscience, 25 (3).
Version
Author's final manuscript
Abstract
The complex connectivity of the mammalian brain underlies its function, but understanding how interconnected brain regions interact in neural processing remains a formidable challenge. Here we address this problem by introducing a genetic probe that permits selective functional imaging of distributed neural populations defined by viral labeling techniques. The probe is an engineered enzyme that transduces cytosolic calcium dynamics of probe-expressing cells into localized hemodynamic responses that can be specifically visualized by functional magnetic resonance imaging. Using a viral vector that undergoes retrograde transport, we apply the probe to characterize a brain-wide network of presynaptic inputs to the striatum activated in a deep brain stimulation paradigm in rats. The results reveal engagement of surprisingly diverse projection sources and inform an integrated model of striatal function relevant to reward behavior and therapeutic neurostimulation approaches. Our work thus establishes a strategy for mechanistic analysis of multiregional neural systems in the mammalian brain.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/S41593-022-01014-8