“It is a myth to assume that the device goes in and the kid starts to figure out how to interpret the sounds,” agreed Nan Bernstein Ratner, EdD, a Professor in the Department of Hearing and Speech Sciences at the University of Maryland in College Park. “It is an awful lot of education and therapy that has to go along so that the child can reconcile the cues that they see on people’s faces with the noises that they’re hearing.”
In patients where ABIs work best, the device could provide a sound signal “that is enough to follow a conversation and even to speak on the telephone,” said Robert V. Shannon, PhD, a Research Professor of Otolaryngology and Biomedical Engineering at the University of Southern California.
Brains and Behavior Are Revealed by Light and CLARITY
Two techniques from the laboratory of Karl Deisseroth, MD, PhD, are helping investigators connect a complicated tangle of brain circuitry with behaviors like fear and addiction. Dr. Deisseroth is the D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University in California.
Dr. Deisseroth is investigating the potential of optogenetics, which uses flashes of light to probe and control brain cells, in mice. About two years ago, Dr. Deisseroth and colleagues began pairing optogenetics with CLARITY, a technique that turns dense tissues like those of the brain transparent.
Optogenetics began with basic research on bacterial and algal opsins, proteins that form channels or pumps in the cell membrane and can be activated by light. Dr. Deisseroth and his colleagues have developed ways to insert these opsins into the brain cells of a mouse and then to activate the proteins with a fiber optic cable attached to the mouse’s head.
In 2007, the researchers used flashes of blue light through the fiber optic cable as a kind of remote control on the mice, which had the opsins placed in a part of the brain that controls motor activity. They could make the mouse continually turn left by flicking on the light, returning the mouse to its own chosen pathway when the light went off. The experiment showed them which sets of neurons were activated during a particular behavior, and has implications for examining and potentially controlling other types of behaviors.
“That’s not the most complex behavior that you could imagine, but it was the beginning, and we’ve now gone from this moment in 2007 to where we can do complex tasks … We’ve been able to use it to come to an understanding of aspects of anxiety, depression, drug abuse, social function and dysfunction, and fear memory” in mice, Dr. Deisseroth said.
Soon after that, Dr. Deisseroth and his colleagues realized that they “were missing a key scientific piece, which is observing the natural patterns of activity in an animal during the course of its normal behavior,” he said. To remedy this gap, they developed a way to insert a fluorescing gene into brain cells that would light up when the cells became active during certain behaviors. This technique helped them distinguish pathways in the brain that control similar but distinct behaviors, such as encountering a new and interesting mouse in a cage or examining a new and interesting toy.
In the past three years, the researchers have gone further in using the techniques to trace some of the fragile connections between brain cells, and in finding ways to zero in on the activity of a single cell. But brain tissue is so dense, and the connections are so complex, that “to look at the detailed wiring, there’s really only one option, and that is to cut [the brain] into millions of thin slices, and then image each of those separately, and then try to reassemble them,” Dr. Deisseroth explained.
Making thin slices is a time-consuming and expensive technique, and Dr. Deisseroth and his colleagues wanted to find a better way to look at an intact brain. Their solution was to invent CLARITY, a technique that secures all of the important molecules in tissue cells—from DNA to proteins—with a special gel while removing the fat molecules that make the brain opaque.
Last year, the researchers used CLARITY to visualize the neural network activated in the mouse brain when it fears pain or anticipates a dose of cocaine. The fluorescent protein that lights up the brain cells involved in these behaviors shows up in distinct patterns that can be seen clearly in the brains once they are removed from the mice and washed clear with CLARITY.