Manipulating nerve cells makes mice ‘see’ something that’s not there

For the first time, researchers have used optogenetics to create a specific visual perception

lab mouse

SNIFFING AROUND A laboratory mouse checks out a device that helps deliver light to specific nerve cells in the brain, activating them in a way that creates a perception. 

Sean Quirin, James Marshel, Cephra Raja and K. Deisseroth/Stanford Univ.

Aiming laser lights into mice’s brains can make them “see” lines that aren’t actually there. The results, described online July 18 in Science, represent the first time scientists have created a specific visual perception with laboratory trickery.

The work is “technically amazing,” says neuroscientist and psychiatrist Conor Liston at Weill Cornell Medicine in New York City. “I think every neuroscientist in this area will look at this with great interest.” The ability to monitor and control precise collections of nerve cells, or neurons, could help unravel big questions, including how certain groups of neurons create experiences.

The experiment used optogenetics, a technique in which laser light activates neurons in the brain (SN: 1/30/10, p. 18). The neurons are genetically tweaked to carry a protein that prompts them to send a signal in response to the light. 

When optogenetics first debuted about 15 years ago, everyone was hoping to achieve this level of precise control over perception, and the behaviors that follow, says Karl Deisseroth, a neuroscientist and psychiatrist who pioneered the technique. “It’s exciting to get to this point,” says Deisseroth, a Howard Hughes Medical Institute investigator at Stanford University. 

Deisseroth and his colleagues first monitored neurons in the brains of mice that were viewing either horizontal or vertical lines. Each mouse had been trained to lick water from a spout in front of it when it saw the orientation of lines it had been trained on. 

The researchers then set out to artificially evoke the same vision of the lines. Initially, the mice were shown very faint real lines. When the lines became so faint that the mice floundered, optogenetic stimulation improved their performance. Then the researchers tested the mice in total darkness, with no visual input whatsoever, and found that a perception of the lines could be created solely with lasers. Stimulating about 20 of the neurons that responded to the real sight caused mice to correctly “see” the right vision, and lick as a result. 

This progression of positive results created “a slowly building crescendo of, ‘Oh my gosh, this is actually working!’” Deisseroth says. 

These artificially stimulated neurons kicked off cascades of other neurons firing in a way that suggested the visual part of the brain was responding as it normally would to a real sight. 

A few key advances led to the experiment’s success, Deisseroth says: Precise lasers that were carefully controlled by liquid crystals, and the discovery of a new light-responsive protein, called ChRmine. Even dim light can activate this protein, a helpful trait because too much light can damage the brain. 

Similar approaches could let scientists create other sorts of perceptions, such as smells, touches and tastes, Deisseroth says. The method may also let researchers control ensembles of neurons that are involved in more complex brain tasks, too. “You could easily imagine using similar tools to study memory, for example,” Liston says.   

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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