Stanford team induces mice to see specific things that aren’t there

By Bruce Goldman

"Hallucinations are spooky and, fortunately, fairly rare. But, a new study suggests, the real question isn't so much why some people occasionally experience them. It's why all of us aren't hallucinating all the time."

So begins my news release about a fascinating study by bioengineer, neuroscientist and practicing psychiatrist Karl Deisseroth, MD, PhD, and his Stanford colleagues, published in Science. Deisseroth is nothing if not inventive: Among other achievements, he's pioneered a world-class technology, optogenetics, enabling researchers to stimulate particular brain cells in freely moving animals with pulses of light, and to observe the resulting effects on the animals' brain function and behavior.

In the new study, an advanced combination of optogenetics and a method of imaging the activity of individual nerve cells (neurons, in science-speak) enabled the scientists to record the activity of several thousand individual neurons simultaneously in mice's brains as the animals were shown random series of horizontal and vertical bars displayed on a screen.

From my release:

The researchers observed and recorded which neurons in the exposed visual cortex [which in both mice and humans is responsible for processing information relayed from the retina] were preferentially activated by one or the other orientation. From these results, the scientists were able to identify dispersed populations of individual neurons that were 'tuned' to either horizontal or vertical visual displays. They were then able to 'play back' these recordings in the form of holograms that produced spots of infrared light on just neurons that were responsive to horizontal, or to vertical, bars.

Now the scientists trained the mice to lick the end of a nearby tube for water whenever they saw a vertical bar -- but not when they saw a horizontal one, or when they saw neither. Once the mice got really good at discriminating between horizontal and vertical bars, the scientists were able to induce tube-licking behavior in the mice simply by playing back the "vertical" program onto the mice's visual cortex. (But the mice wouldn't lick the tube if the "horizontal" program was played instead.)

"Not only is the animal doing the same thing, but the brain is, too," Deisseroth told me when I interviewed him about the study. "So we know we're either recreating the natural perception or creating something a whole lot like it."

Optogenetically stimulating about 20 neurons (fewer in some cases) selected only for being responsive to the right orientation was enough to produce the same neuronal activity and animal behavior that actually displaying the vertical or horizontal bar did.

"A mouse brain has millions of neurons; a human brain has many billions," Deisseroth said. "If just 20 or so can create a perception, then why are we not hallucinating all the time, due to spurious random activity?"

Deisseroth said his study's findings imply that the mammalian cortex is somehow poised to be responsive to an amazingly low number of cells without causing spurious perceptions in response to noise.

That's evidently true almost all the time in a healthy brain (plus or minus the odd UFO sighting). But more than 1 in 100 of us experiences all-too-frequent unwanted apparitions. The study's findings, and methodology, could lead to a better understanding of the hallucinations that afflict schizophrenics. And, one hopes, to better treatments for them.

Other potential applications, ranging from the frivolous to the profound, abound, although some of them may be several decades off if not entirely whimsical. Getting the brain to "see" a vertical bar that isn't really there may be a baby step, but wouldn't it be fun to record and play back the crazy dream you had last night?