Rabies viruses reveal wiring in transparent brains

Scientists under the leadership of the University of Bonn have harnessed rabies viruses for assessing the connectivity of nerve cell transplants: coupled with a green fluorescent protein, the viruses show where replacement cells engrafted into mouse brains have connected to the host neural network. 

A clearing procedure which turns the brain into a 'glass-like state' and light sheet fluorescence microscopy are used to visualize host-graft connections in a whole-brain preparation. The approach opens exciting prospects for predicting and optimizing the ability of neural transplants to functionally integrate into a host nervous system.

Many diseases and injuries result in a loss of nerve cells. Scientists are working on tackling this challenge by transplanting neurons. In Parkinson's disease, for instance, this is attempted with implanted dopamine-producing nerve cells. The key question for such techniques is whether the implanted cells actually connect with the existing neural network of the host brain and thus compensate the functional loss.

Team led by Prof. Brüstle developed a new technique: "This enables the connection of implanted cells in the entire brain to be visualized in high resolution." The basis of this technology is provided by genetically altered rabies viruses. The researchers are exploiting the fact that these viruses spread backwards via nerve cell junctions -- called synapses.

The genetically altered rabies virus, which is no longer dangerous to humans, carries a fluorescent protein. Upon infection of the graft, the transplanted neurons turn green. At the same time, the 'green' virus spreads backwards across established synapses to connected host neurons, which are also turning green.