Recombinant Rabies Virus Vectors Developed to Advance Neural Circuit Mapping

A team of researchers from the University of California, Irvine has engineered 20 novel recombinant rabies viral vectors for neural circuit mapping. According to the team, these new vectors offer a range of significant advantages over existing tools, including the ability to detect microstructural changes in models of aging and Alzheimer’s disease brain neurons.

The research, detailed in Molecular Psychiatry, presented proof-of-concept data demonstrating the power of these new vectors, which express a range of improved fluorescent proteins to provide expanded multi-scale multi-modal capabilities.

To create the new vectors, the team harnessed the tendency of rabies infections to target the nervous system and were able to engineer forms of the rabies virus that are coupled to sensors and other payloads—for example, some respond to light by turning bright green and act as tracers that map brain circuits.

“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 of the study. “These new variants significantly enhance the capability and reach of neural labeling and circuit mapping across microscopic and macroscopic imaging scales and modalities, including 3D light and X-ray microscopy.”

These new recombinant viral vectors are designed to target very specific components of neuron biology in order to analyze pathological changes that occur during Alzheimer’s disease and other brain diseases. They can be targeted to specific sub-cellular locations and organelles, as well as live imaging of neuronal activities using calcium indicators.