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 language | English |
|---|---|
| Pages (from-to) | 390-398 |
| Number of pages | 9 |
| Journal | Nature Neuroscience |
| Volume | 25 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2022 Mar |
Bibliographical note
Funding Information:This research was funded by NIH grant numbers R01 DA038642, R24 MH109081, UF1 NS107712 and U01 NS103470 and a grant from the MIT Simons Center for the Social Brain to A.J. S.G. was supported by an HHMI International Student Research Fellowship and Sheldon Razin Fellowship from the McGovern Institute for Brain Research. N.L. was supported by a Stanley Fahn Research Fellowship from the Parkinson’s Disease Foundation. M.S. was the recipient of a Marie Curie Individual Fellowship from the European Commission. T.X. was a visiting student from the Beijing University of Chinese Medicine, funded by a scholarship from the China Scholarship Council. J.I.D. was supported by the Johnson & Johnson UROP Scholars Program at MIT. We are grateful to S. Lall and B. Sabatini for comments on the manuscript, and to A. Devor, I. Wickersham and H. Sullivan for conversations. We also thank L. McLain for providing CAD cells and T. Poulos of the University of California, Irvine and P. Ortiz de Montellano at the University of California, San Francisco for providing NOS constructs. R. Neve of the Massachusetts General Hospital is acknowledged for production of HSV vectors.
Funding Information:
This research was funded by NIH grant numbers R01 DA038642, R24 MH109081, UF1 NS107712 and U01 NS103470 and a grant from the MIT Simons Center for the Social Brain to A.J. S.G. was supported by an HHMI International Student Research Fellowship and Sheldon Razin Fellowship from the McGovern Institute for Brain Research. N.L. was supported by a Stanley Fahn Research Fellowship from the Parkinson?s Disease Foundation. M.S. was the recipient of a Marie Curie Individual Fellowship from the European Commission. T.X. was a visiting student from the Beijing University of Chinese Medicine, funded by a scholarship from the China Scholarship Council. J.I.D. was supported by the Johnson & Johnson UROP Scholars Program at MIT. We are grateful to S. Lall and B. Sabatini for comments on the manuscript, and to A. Devor, I. Wickersham and H. Sullivan for conversations. We also thank L. McLain for providing CAD cells and T. Poulos of the University of California, Irvine and P. Ortiz de Montellano at the University of California, San Francisco for providing NOS constructs. R. Neve of the Massachusetts General Hospital is acknowledged for production of HSV vectors.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
All Science Journal Classification (ASJC) codes
- Neuroscience(all)