Functional dissection of neural circuitry using a genetic reporter for fMRI

Souparno Ghosh, Nan Li, Miriam Schwalm, Benjamin B. Bartelle, Tianshu Xie, Jade I. Daher, Urvashi D. Singh, Katherine Xie, Nicholas DiNapoli, Nicholas B. Evans, Kwanghun Chung, Alan Jasanoff

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)390-398
Number of pages9
JournalNature neuroscience
Volume25
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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