For years, the human brain has been compared to a computer—but it is a computer without a wiring diagram. Researchers simply do not know how the billions of neurons in the brain are connected to one another, and without this information they cannot fully understand how the brain’s structure gives rise to perception and behavior. Now, for the first time, scientists have found a way to track the connections between a single neuron and other cells—a discovery that could eventually lead to a 3-D map of the brain’s wiring.
A team led by Edward M. Callaway of the Salk Institute for Biological Studies in San Diego illuminated neuronal links by modifying the rabies virus. The investigators remove the gene for a protein that allows the virus to move between cells and let the crippled virus infect each nerve cell they want to study. Then, by inserting the viral gene into these neurons, they cause each brain cell to manufacture the missing protein, thereby restoring the virus’s ability to move into directly connected cells. From there, the virus cannot spread any farther because its new neuronal hosts do not make the vital protein. Within a few days, the fluorescent-dyed virus creates a glowing map of a single neuron’s every connection.
“Circuitry is the basis for all complex neural function,” Callaway says. “Without knowing the circuit, there is no way to know how the brain works.” Although every brain has different synaptic connections resulting from individual experiences, the researchers believe they will be able to identify common circuits and eventually figure out the function of specific neuronal pathways. The team hopes to work with live animals within months and to begin to construct “a precise wiring diagram of the mouse brain.”
A team led by Edward M. Callaway of the Salk Institute for Biological Studies in San Diego illuminated neuronal links by modifying the rabies virus. The investigators remove the gene for a protein that allows the virus to move between cells and let the crippled virus infect each nerve cell they want to study. Then, by inserting the viral gene into these neurons, they cause each brain cell to manufacture the missing protein, thereby restoring the virus’s ability to move into directly connected cells. From there, the virus cannot spread any farther because its new neuronal hosts do not make the vital protein. Within a few days, the fluorescent-dyed virus creates a glowing map of a single neuron’s every connection.
“Circuitry is the basis for all complex neural function,” Callaway says. “Without knowing the circuit, there is no way to know how the brain works.” Although every brain has different synaptic connections resulting from individual experiences, the researchers believe they will be able to identify common circuits and eventually figure out the function of specific neuronal pathways. The team hopes to work with live animals within months and to begin to construct “a precise wiring diagram of the mouse brain.”
