Sunday, September 25, 2011

How Viruses Can Be Engineered to Trace Neural Connections

In looking for ways to map the connections of neurons, scientists are turning to viruses – in particular, those that have evolved to infect neurons and to spread from one to another through the synaptic connections between them. One of these is the deadly rabies virus – a specialist in infecting neurons. Rabies is typically transmitted from one infected animal to another through saliva, often via a bite, which releases viral particles that infect peripheral neurons. From there, it spreads backwards into the spinal cord and brain, passing from the initially infected neurons into every neuron that connects to them. This continues in the next neurons, resulting in the rapid spread of infection throughout the entire nervous system.

The fact that the virus can spread from an infected neuron to other neuronsconnected to it makes it an almost perfect vector for tracing these connections in the brains of experimental animals. To make it perfect required some modifications.

First, using the tools of molecular biology, researchers have modified the genomeof the rabies virus, so that, as well as its own genes, the virus now carries so-called marker proteins, like the well-known green fluorescent protein from jellyfish. When ultraviolet light is shone on this protein, it fluoresces, giving off avivid green light. Neurons infected with the virus (either directly or via synaptic connections) can thus be beautifully visualised.

A major problem, however, is the rabies virus is too efficient – it continues to spread to all the neurons connected to each of the neurons connected to the first neuron, obscuring the pattern we are interested in. To get around this, the virus had to be crippled by removing one of the genes it needs to spread.


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