Painting Neural Circuitry With a Viral Brush: Are the Neighbors Green?

Note: This is the second installment of a two-part series describing the use of engineered rabies viruses in the elucidation of neural circuits. These columns appear in the Psychiatric Times. Learn about Brain Rules here.

In last month’s column (“Painting Neural Circuitry With a Viral Brush,” Psychiatric Times, October 2008), I used Michelangelo’s famous fresco, “Hand of God Giving Life to Adam” on the ceiling of the Sistine Chapel as a metaphor to introduce a series of technologies that have allowed researchers to map the complex interactions of neural connections in continuously functioning neural tissues. This technology promises to deliver accurate synaptic associations—one finger to another—at a very high level of resolution.

These extraordinary cartographic techniques involve exploiting the natural ability of the rabies virus to set up productive infections in neural tissues. For simplicity’s sake, we are examining the genetic manipulation of hypothetical “Neuron A” and its reaction to a previously engineered rabies virus. Although the manipulations to the virus are complex, using the data obtained, researchers seek to answer a simple, seemingly innocuous question: Are the neighbors green?

In case you do not have last month’s column handy, let me briefly review the life cycle of the rabies virus and reexamine the reengineered virus and Neuron A. We can then turn directly to the data.

Rabies virus

As mentioned last month, the rabies virus has several biological aspects that make it an ideal delivery device for working with living neural tissues. Once inside a nerve cell, the virus sets up a manufacturing site to create more viruses, like any typical virus. At maturity, however, these progenies jump to neighboring neurons, which allows the virus to spread along specific neural routes. This life cycle is handy if you are interested in synaptic connections throughout the body.

The infection can start in the peripheral nervous system and then jump the stout molecular border that separates it from the CNS. (That is why a bite anywhere on the body can result in a catastrophic brain infection.) If one could find a way to follow the virus, one could identify the routes by which it travels.

Aspects of this jumping ability were exploited in the circuit-mapping experiments we are about to review. Both virus and cell had to be genetically manipulated in 3 different ways for the experiment to work.

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