Genetic Expression Technique Based on Light Switching Proteins Helps Uncover Function of Individual Neurons

At UC Berkeley, researchers have developed a light switch technique that can identify which neurons are responsible for a given activity. The scientists genetically engineered zebrafish to produce a light sensitive protein that can be used to activate neurons with a focused beam of colored light. By applying light to various neurons, they were able to see what activity they initiated.

Currently, scientists often determine a neuron’s function via correlation. If a group of neurons activates every time an animal performs a certain behavior, then chances are those neurons control that behavior. The same goes if the neurons are disrupted: if the behavior stops, then the affected neurons likely control it.
The key to the scientists’ success is an artificial, light-activated protein they developed a few years ago. The protein can be genetically engineered to express in a neuron or other type of cell and function as an optical switch. Zap the protein with one color of light, and it switches on and activates its host neuron. Zap it with another color of light, and it turns off and the neuron becomes dormant.
To test the light-activated protein, Isacoff [Ehud Isacoff, a UC Berkeley biophysicist] and colleagues used it to search for the cell that drives the neural circuit that mediates swimming in larval zebrafish.
First, they randomly expressed the protein in the genome of hundreds of larval zebrafish. Some light-activated switches popped up in muscle cells, some in bone cells, and some in the central nervous system.
Next, they chose only those fish in which the light-activated protein was expressed in neural cells in the spinal cord, some of which are known to control locomotion.
They then zapped these fish with light. Like dutiful servants, a handful of fish spontaneously flicked their tails side to side in a swimming motion. Further analysis led the scientists to the neural source of this behavior: all of the swimmers had the optical switch expressed in a cell called the Kolmer-Agduhr neuron, whose existence has been known for more than 75 years, but whose function had remained a mystery.
“Our technique allows us to identify previously unknown parts of neural circuits that control a behavior,” says Isacoff. “And this approach can be broadly used. What we have done with locomotion can be done with any behavior and in many biological systems. “

Here’s a larval zebrafish flicking its tail in a swimming motion after being exposed to UV light: