July 11, 2005
La Jolla, CA – For many years, scientists tried to glean information about the nervous system by recording the electrical activity of one brain cell at a time. Because even the simplest functions of the nervous system involve many thousands of neurons, recording the activity of individual or only a handful of nerve cells does not provide a full picture.
So, in collaboration with an international group of high-energy physicists, neurobiologists at the Salk Institute for Biological studies developed a microscopic electrode array that allows them to monitor the activity of hundreds of nerve cells simultaneously.
Their research lays the technological and biological groundwork for the development of visual prosthetic devices that, one day, could restore some degree of vision to people whose retina, a thin tissue lining the back of the eye, has been damaged by disease or trauma.
“Our device allows us to figure out what it takes to deliver the right kind of information to the brain. Hopefully, in five years, what we learn now will be integrated in visual prosthetic devices,” says E.J. Chichilnisky, an Associate Professor in the Systems Neurobiology Laboratories and senior author of the study, which is published in the July issue of the Journal of Neurophysiology.
In simplified terms, vision is generated when light entering the eye is converted by the retina into a set of highly processed electrical signals that are carried by the optic nerve to the brain’s visual cortex. When the retina is damaged, this circuit is interrupted and blindness results. Retinal implants are designed to bypass the damaged retina with the help of tiny electrode arrays that are used to induce electrical signals in nerve cells in the back of the eye.
During the past few years, the first prototypes of retinal prosthetic devices have been implanted in a handful of people. But the vision produced by these implants, which contain only 16 electrodes, is extremely crude and allows the patients only to discriminate between flashes of light.
In collaboration with the Salk researchers, Alan Litke, a particle physicist at the Santa Cruz Institute for Particle Physics at the University of California in Santa Cruz, and his team developed a microscopic electrode array that is 10 times smaller but is studded with more than 30 times the number of electrodes compared to current implants. Each of the 512 electrodes measures only 5 micrometers across or about 1/20 of the width of a human hair. While this array is not suitable for implantation in humans, it can be used to study how patterns of electrical stimulation affect neurons in excised retina.
Salk neurobiologists Eric S. Frechette and Chichilnisky used the 512-electrode array to study how precisely the retina conveys information about moving objects to the brain. They placed a tiny piece of retina on top of the array and stimulated the photoreceptors in the retina with dynamic visual images while the electrode array recorded the signals generated in response to the moving stimuli. By comparing the visual input with the electrical output of the retina, the researchers could study the neural code used by the retina to relay meaningful information to the brain.
“The retina communicates movement not through a single cell but through a pattern of activity involving many cells. As the stimulus, such as a moving car or running gazelle, moves a corresponding wave of activity crosses the retina,” explains Chichilnisky. He adds that “until we could record directly from hundreds of cells, it was impossible to tell how accurately the retina transmitted to the brain information about speed and direction of movement.”
Now they can. Based on the activity pattern generated by the retina, the neurobiologists were able to estimate the speed of the projected moving object with a surprising accuracy of 99 percent. “In everyday experience knowing how fast and in which direction things are moving is crucial, just think of cars on a five lane highway or a gazelle that tries to evade a predator,” says Chichilnisky.
In addition, the technology is potentially applicable to the study of other neural circuits in the brain.
Currently, Chichilnisky’s team is using the microscopic electrode array to induce electrical signals in retinal cells. Based on what they have learned from their recording studies, they will try to mimic the neural code used by the retina to transmit visual information to the brain in future studies.
“Hopefully, we will be able to recreate a meaningful pattern of activity in many nerve cells. This will lay the foundation for building devices that allow blind human subjects to do what they want to do, such as cross a street or simply not bump into things,” says Chichilnisky.
Scientists at the Santa Cruz Institute for Particle Physics who have contributed to the paper include physics graduate student Matthew Grivich, postgraduate researcher Dumitru Petrusca, and postdoctoral physicist Alexander Sher. Important contributions to the technology development were also made by Wladek Dabrowski and his integrated circuit design team at the AGH University of Science and Technology in Krakow, Poland.
The work was in part enabled by a Salk Institute Innovation grant, funded through contributions from private donors.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, founded the Institute in 1960 on land donated by the City of San Diego and with the financial support of the March of Dimes.
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