With the flick of a precisely placed light switch, mice can be induced to cower in a corner in fear or bravely explore their environment. The study highlights the power of optogenetics technology—which allows neuroscientists to control genetically engineered neurons with light—to explore the functions of complex neural wiring and to control behavior.
In the study, Karl Deisseroth and collaborators at Stanford University identified a specific circuit in the amygdala, a part of the brain that is central to fear, aggression, and other basic emotions, that appears to regulate anxiety in rodents. They hope the findings, published today in the journal Nature, will shed light on the biological basis for human anxiety disorders and point toward new targets for treatment.
“We want to conceptualize psychiatric disease as real physical entities with physical substrates,” says Deisseroth. “Just like people who have asthma have reactive airways, people with anxiety disorders may have an underactive projection in the amygdala.”
The researchers engineered mice to express light-sensitive proteins in specific cells in the amygdala that send out neural wires, known as axons, to different substructures. Using a specially designed fiber-optic cable implanted in the animal’s brain, researchers found that aiming the light to activate one specific circuit had an immediate and potent effect on the animal’s behavior.
“I’ve never seen anything like it,” says Kay Tye, a postdoctoral researcher in Deisseroth’s lab and lead author on the study. Mice are naturally fearful of exploring open areas, she explains. Under normal circumstances, the animal “will poke its nose out and then scurry into a corner,” says Tye. “But when you turn on the light, the animal begins exploring the platform with no visible signs of anxiety. Then you turn the light off, and it scurries back in to the corner.”
The researchers could induce the opposite effect using a light-sensitive protein that silences the cells instead of activating them.
Shining light on the bodies of the cells, which in turn activates axons in multiple circuits, had no effect on the animals’ behavior, highlighting how important it is to be able to target individual circuits in the brain.