New rabies viral resources for multi-scale neural circuit mapping

Alexis Bouin; Ginny Wu; Orkide O Koyuncu; Qiao Ye; Keun-Young Kim; Michele Y Wu; Liqi Tong; Lujia Chen; Sebastien Phan; Mason R Mackey; Ranjan Ramachandra; Mark H Ellisman; Todd C Holmes; Bert L Semler; Xiangmin Xu

doi:10.1038/s41380-024-02451-6

New rabies viral resources for multi-scale neural circuit mapping

Mol Psychiatry. 2024 Feb 14. doi: 10.1038/s41380-024-02451-6. Online ahead of print.

Authors

Alexis Bouin^#¹, Ginny Wu^#², Orkide O Koyuncu¹, Qiao Ye^{2

3}, Keun-Young Kim⁴, Michele Y Wu¹, Liqi Tong², Lujia Chen^{2

3}, Sebastien Phan⁴, Mason R Mackey⁴, Ranjan Ramachandra⁴, Mark H Ellisman⁴, Todd C Holmes^{5

6}, Bert L Semler^{7

8}, Xiangmin Xu^{9

10

11

12}

Affiliations

¹ Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA, 92697, USA.
² Department Anatomy & Neurobiology, School of Medicine, University of California, Irvine, CA, 92697, USA.
³ Department Biomedical Engineering, University of California, Irvine, CA, 92697, USA.
⁴ The National Center for Microscopy and Imaging Research (NCMIR) and the Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
⁵ Physiology & Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA.
⁶ The Center for Neural Circuit Mapping, University of California, Irvine, CA, 92697, USA.
⁷ Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA, 92697, USA. blsemler@uci.edu.
⁸ The Center for Neural Circuit Mapping, University of California, Irvine, CA, 92697, USA. blsemler@uci.edu.
⁹ Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA, 92697, USA. xiangmix@uci.edu.
¹⁰ Department Anatomy & Neurobiology, School of Medicine, University of California, Irvine, CA, 92697, USA. xiangmix@uci.edu.
¹¹ Department Biomedical Engineering, University of California, Irvine, CA, 92697, USA. xiangmix@uci.edu.
¹² The Center for Neural Circuit Mapping, University of California, Irvine, CA, 92697, USA. xiangmix@uci.edu.

^# Contributed equally.

PMID: 38355784
DOI: 10.1038/s41380-024-02451-6

Abstract

Comparisons and linkage between multiple imaging scales are essential for neural circuit connectomics. Here, we report 20 new recombinant rabies virus (RV) vectors that we have developed for multi-scale and multi-modal neural circuit mapping tools. Our new RV tools for mesoscale imaging express a range of improved fluorescent proteins. Further refinements target specific neuronal subcellular locations of interest. We demonstrate the discovery power of these new tools including the detection of detailed microstructural changes of rabies-labeled neurons in aging and Alzheimer's disease mouse models, live imaging of neuronal activities using calcium indicators, and automated measurement of infected neurons. RVs that encode GFP and ferritin as electron microscopy (EM) and fluorescence microscopy reporters are used for dual EM and mesoscale imaging. These new viral variants significantly expand the scale and power of rabies virus-mediated neural labeling and circuit mapping across multiple imaging scales in health and disease.

Grants and funding

R01 FD007478/FD/FDA HHS/United States