For a decade, the rabies virus, which claims some 59,000 human lives a year, has become an exceptional tool for neuroscientists, since its way of invading the brain – from neuron to neuron and between the different parts of these – allows you to draw a map of the connections or synapses that connect nerve cells. Often times, researchers insert a fluorescent protein into the pathogen to make its trail light. The problem lies precisely in that: in that it is a pathogenic agent and rapidly deteriorates the neurons of laboratory animals. The experiments have an expiration date of approximately two weeks .
But this serious limitation could have its days numbered. Researchers from the Massachusetts Institute of Technology (MIT) and the Allen Institute for Brain Science have just created a “harmless” version of the rabies virus: once it infects the nerve cell it does not reproduce , allowing it to release its cargo genetics – conveniently prepared by scientists – without the usual harmful effects.
This was explained by Ian Wickersham, from MIT’s McGovern Institute for the Study of the Brain and one of the main people responsible for the research, which is published in the journal Nature Neuroscience : “Before, viruses replicated like crazy in infected neurons , which was not exactly good for them. However, with second-generation viral microorganisms, the cells appear normal and behave normally for at least four months , as we have had the opportunity to verify. And perhaps throughout the life of the animal studied ”.
Illuminated neurons
This advance is the culmination of a work that Wickersham himself began in 2007, when by deleting one of the five genes of the virus, they managed to spread it only to neurons directly connected to the infected cell and thus trace the brain wiring. With the new technique, scientists could also manipulate groups of neurons thanks to optogenetics, that is, by inserting genes into cells that encode light-sensitive proteins. So they can turn entire groups of them on or off and find out what role they play .
Now, Wickersham and his colleagues have deactivated the viral gene responsible for the polymerase enzyme, which is essential for the microorganism’s DNA to be transcribed. That takes away, as they have observed, its ability to destroy neurons, although it has unwanted side effects: the rabies virus also loses its steam to express the genes that scientists introduce to it , such as those that generate the photosensitive proteins necessary for aforementioned optogenetic techniques.
The trick then consists of inserting into the viral microorganism the coding gene for another substance, called cre recombinase. This in turn activates another gene in transgenic mice with the ability to manufacture fluorescent proteins or another type of marker that makes it possible to visualize the functioning and interconnection of neurons. In short, pure biochemical engineering to illuminate the most intimate recesses of the brain .
