In Optogenetics, Buttons for Neural Switchboards - NYTimes.com

Treating anxiety no longer requires years of pills or psychotherapy. At least, not for a certain set of bioengineered mice.

In a study recently published in the journal Nature, a team of neuroscientists turned these high-strung prey into bold explorers with the flip of a switch.

The group, led by Dr. Karl Deisseroth, a psychiatrist and researcher at Stanford, employed an emerging technology called optogenetics to control electrical activity in a few carefully selected neurons.

First they engineered these neurons to be sensitive to light. Then, using implanted optical fibers, they flashed blue light on a specific neural pathway in the amygdala, a brain region involved in processing emotions.

And the mice, which had been keeping to the sides of their enclosure, scampered freely across an open space.

While such tools are very far from being used or even tested in humans, scientists say optogenetics research is exciting because it gives them extraordinary control over specific brain circuits — and with it, new insights into an array of disorders, among them anxiety and Parkinson's disease.

Mice are very different from humans, as Dr. Deisseroth (pronounced DICE-er-roth) acknowledged. But he added that because "the mammalian brain has striking commonalities across species," the findings might lead to a better understanding of the neural mechanisms of human anxiety.

David Barlow, founder of the Center for Anxiety and Related Disorders at Boston University, cautions against pushing the analogy too far: "I am sure the investigators would agree that these complex syndromes can't be reduced to the firing of a single small neural circuit without considering other important brain circuits, including those involved in thinking and appraisal."

But a deeper insight is suggested by a follow-up experiment in which Dr. Deisseroth's team directed their light beam just a little more broadly, activating more pathways in the amygdala. This erased the effect entirely, leaving the mouse as skittish as ever.

This implies that current drug treatments, which are far less specific and often cause side effects, could also in part be working against themselves.

David Anderson, a professor of biology at the California Institute of Technology who also does research using optogenetics, compares the drugs' effects to a sloppy oil change. If you dump a gallon of oil over your car's engine, some of it will dribble into the right place, but a lot of it will end up doing more harm than good.

"Psychiatric disorders are probably not due only to chemical imbalances in the brain," Dr. Anderson said. "It's more than just a giant bag of serotonin or dopamine whose concentrations sometimes are too low or too high. Rather, they likely involve disorders of specific circuits within specific brain regions."

So optogenetics, which can focus on individual circuits with exceptional precision, may hold promise for psychiatric treatment. But Dr. Deisseroth and others caution that it will be years before these tools are used on humans, if ever.

For one, the procedure involves bioengineering that most people would think twice about. First, biologists identify an "opsin," a protein found in photosensitive organisms like pond scum that allows them to detect light. Next, they fish out the opsin's gene and insert it into a neuron within the brain, using viruses that have been engineered to be harmless —"disposable molecular syringes," as Dr. Anderson calls them.

There, the opsin DNA becomes part of the cell's genetic material, and the resulting opsin proteins conduct electric currents — the language of the brain — when they are exposed to light. (Some opsins, like channelrhodopsin, which responds to blue light, activate neurons; others, like halorhodopsin, activated by yellow light, silence them.)

Finally, researchers delicately thread thin optical fibers down through layers of nervous tissue and deliver light to just the right spot.

Thanks to optogenetics, neuroscientists can go beyond observing correlations between the activity of neurons and an animal's behavior; by turning particular neurons on or off at will, they can prove that those neurons actually govern the behavior.

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http://www.nytimes.com/2011/05/17/science/17optics.html?pagewanted=all