Painting Neural Circuitry With a Viral Brush

The "Molecules of the Mind" column appears monthly in the Psychiatric Times. Learn more about "Brain Rules" at www.brainrules.net.

We often describe neural connections in the brain as if they were a cellular version of Michelangelo’s famous painting “Hand of God Giving Life to Adam,” on the ceiling of the Sistine Chapel. Like the painting, the neural explanations usually invoke 2 outstretched limbs nearly touching each other—one presynaptic,one postsynaptic—that are separated by their 20-nanometer synaptic cleft.

Such descriptions hardly depict the neurological reality of the brain, of course. A better metaphor for 2 neurons might be 2 trees that have been uprooted and turned 90 degrees so their root systems face each other. Then, some Paul Bunyan–type character jams both ends together. Thousands of connections from 1 tree now face thousands of connections from the other. Multiply those 2 neurons by thousands while all their root systems are still jammed together with the same Bunyanesque enthusiasm and you can visualize an approximation of the real world of brain wiring. Not as elegant as 2 limbs—and not as simple either.

How can we understand the way all those myriad connections work together to produce the various neurological abilities of the brain? Given its complexity, the task is enormous. Since we are only in the initial stages, it will take a long time before we will be able to map structure to function.

Like any exploration in its initial stages, we first need a good map—a schematic that shows how each slender dendritic branch interacts with a specific nerve cell. From Nissl and Weigert stains to the canonical Golgi stain, we have traditionally used dye technology to help us visualize these interactions. However, there are severe limitations to most of these staining technologies that center around their inability to make visible all the connections that actual neurons possess. We need something with far greater resolution and, perhaps, with a bit more elegance.

The topic of this column and the next is a technology that promises to deliver just such circuit diagrams at a very high level of resolution. The technology involves the exploration of viruses, which in their native form cause some pretty tough diseases (eg, rabies, cancer). Thoughtful genetic engineering has transformed these viruses’ job description from fearful disease inducer to doughty cartographer cartographer. We are going to follow how this transformation has occurred.

Download the full column (PDF), which appears in the October issue of Psychiatric Times.