A drug-like molecule has been found to let researchers control movements in mice and fish with flashes of light. Unlike similar experiments using a light-based technique known as optogenetics, the new method doesn’t require researchers to genetically engineer animals in order to achieve the neural control.
A study published online in today’s Nature Chemical Biology describes a novel approach for controlling neurons and behaviors with light. Such techniques are powerful research tools for understanding the brain, and may one day be used therapeutically. Today’s report describes a method for using light to control neuronal activity in unmodified animals. Fish given a small molecule called “optovin” will move around very quickly in response to a flash of light, report Massachusetts General Hospital’s David Kokel and colleagues.
The response is not dependent on the fish perceiving the light—embryonic fish treated with the chemical react to light even before their eyes develop, and decapitated adults respond as well. The compound instead binds to pain sensation receptors on the fish’s body, and when activated by light, it elicits fast movements.
The team screened through 10,000 different compounds—each dissolved in a small well with not-yet-hatched zebrafish—before they found one that drastically changed the animals’ behavior in response to light. The compound also works on mice—if optovin is rubbed onto the ears of mice, a flash of light will cause the mice to shake their heads.
The team determined that optovin docks onto a specific kind of protein channel that sits in the membrane of nerve cells that are the first to respond to pain. Researchers could use optovin in experiments to study pain; they also think it could be useful in treating pain, says Kokel. “If you over-activate these channels, they become desensitized,” he says.
But optovin cannot control the behavior of other kinds of neurons, which is a disadvantage compared to optogenetics. Ed Boyden, a neuroscientist at MIT who has developed optogenetics tools, points out that the genetic engineering-based method gives researchers more flexibility. “A chief utility of our … optogenetic tools is that we can target them to practically any class of neurons, enabling them specifically to be activated and silenced by light,” Boyden says.
However, it’s possible, says Kokel, that researchers could identify compounds other than optovin that could regulate the protein channels that control neuron behavior. “You could have a whole tool box of compounds that activate different channels,” he says.