Positive Technology Journal

While scientists know something about the chemical imbalances underlying depression, it's still unclear exactly which cells, or networks of cells, are responsible for it. In order to identify the circuits involved in such diseases, scientists must be able to turn neurons on and off. Standard methods, such as electrodes that activate neurons with jolts of electricity, are not precise enough for this task, so Deisseroth, postdoc Ed Boyden (now an assistant professor at MIT; see "Engineering the Brain"), and graduate student Feng Zhang developed a neural controller that can activate specific sets of neurons.

They adapted a protein from a green alga to act as an "on switch" that neurons can be genetically engineered to produce (see "Artificially Firing Neurons," TR35, September/October 2006). When the neuron is exposed to light, the protein triggers electrical activity within the cell that spreads to the next neuron in the circuit. Researchers can thus use light to activate certain neurons and look for specific responses--a twitch of a muscle, increased energy, or a wave of activity in a different part of the brain.

Deisseroth is using this genetic light switch to study the biological basis of depression. Working with a group of rats that show symptoms similar to those seen in depressed humans, researchers in his lab have inserted the switch into neurons in different brain areas implicated in depression. They then use an optical fiber to shine light onto those cells, looking for activity patterns that alleviate the symptoms. Deisseroth says the findings should help scientists develop better antidepressants: if they know exactly which cells to target, they can look for molecules or delivery systems that affect only those cells. "Prozac goes to all the circuits in the brain, rather than just the relevant ones," he says. "That's part of the reason it has so many side effects."