A research team led by the University of California, Irvine has created 20 new recombinant rabies viral vectors for neural circuit mapping that offer several significant advantages over existing tools, including in brain neurons of aging models and Alzheimer’s disease. Ability to detect microstructural changes. .

The study was published online today in the journal Molecular psychiatry, presented proof-of-concept data demonstrating the power of these new vectors, which express a range of fluorescent proteins optimized to provide expanded multiscale multimodal capabilities. Naturally occurring rabies infections target the nervous system. Scientists have used this phenomenon to create engineered forms of the rabies virus that are attached to sensors and other payloads — for example, some that respond to light and turn bright green to map brain circuits. They act as tracers.

“Viral genetic tools are critical for improving anatomical mapping and functional studies of cell-type-specific and circuit-specific neural networks,” said Xiangmin Xu, co-corresponding author and UCI Chancellor’s Professor of Anatomy and Neurobiology. Director of the Center for Neural said. Circuit Mapping. “These new variants significantly increase the capacity and accessibility of neural labeling and circuit mapping at microscopic and macroscopic imaging scales and modalities, including 3D light and X-ray microscopy. We are making these new tools available to the neuroscience community through our established service. will be made readily available on the CNCM platform.”

These new recombinant viral vectors are designed to target very specific components of neuron biology to analyze the pathological changes that occur during Alzheimer’s disease and other brain diseases. They can be targeted to specific subcellular locations and organelles, as well as live imaging of neuronal activity using calcium indicators. The team performed imaging analysis of mouse brains to demonstrate the discovery power of these new devices.

“These advanced tools have enormous potential to understand neural circuitry in both normal and pathological conditions and offer the ability to target specific brain regions with precise peptides or proteins to modulate neuronal function for targeted therapeutic strategies. can be modulated,” said Bert Semler. – Corresponding author and UCI Distinguished Professor of Microbiology and Molecular Genetics.

Alexis Bouin, Ph.D. and Jane Wu are co-first authors who led and contributed to this project. Additional team members include Orkide Koyuncu, assistant professor of microbiology and molecular genetics. Qiao Ye, graduate student; Michelle Wu, Liqi Tong, Ph.D., and Lujia Chen, Ph.D., members of the Xu lab, and Todd Holmes, professor of physiology and biophysics. Leveraging the extensive collaborative network of the UCI Center for Neural Circuit Mapping, UCSD team members include Keun-Young Kim, Sebastien Phan, Mason R. Mackey, Ranjan Ramachandra, and Distinguished Professor Mark H. Ellisman.

This work was supported by National Institutes of Health Grants RF1MH120020, R01FD007478, R35GM127102, R24GM137200, U24NS120055, and R01DA038896; and National Science Foundation Grant NSF2014865-UTA20-00890.