Biologists and engineers at the Massachusetts Institute of Technology (MIT) in Cambridge, have created a new device that can deliver precise points of light to a 3-D section of living brain tissue.
The work is a step forward for a relatively new but promising technique that uses gene therapy to turn individual brain cells on and off with light.
Scientists can use the new 3-D “light switch” to better understand how the brain works. It might also be used one day to create neural prostheses that could treat conditions such as Parkinson’s disease and epilepsy.
The technique of manipulating neurons with light is only a few years old, but the authors estimate that thousands of scientists are already using this technology, called optogenetics, to study the brain. In optogenetics, researchers first sensitize select cells in the brain to a particular color of light. Then, by illuminating precise areas of the brain, they are able to selectively activate or deactivate the individual neurons that have been sensitized.
Ed Boyden, a synthetic biologist at MIT and co-lead researcher on the paper, is a pioneer of this emerging field, which he says offers the ability to probe connections in the brain.
Unlike the previous, 1-D versions of this light-emitting device, the new tool delivers light to the brain in three dimensions, opening the potential to explore entire circuits within the brain. So far, the 3-D version has been tested in mice, although Boyden and colleagues have used earlier optogenetic technologies with non-human primates as well.
One of the advantages of optogenetics is that this technology allows scientists to focus on one particular type of neuron without affecting other types of neurons in the same area of cortex. Probes that deliver electricity to the brain can manipulate neurons, but they cannot target individual kinds of cell, Boyden said.
Drugs can turn neurons on or off as well, he added, but not on such a quick time scale or with such a high degree of control. In contrast, the new 3-D array is precise enough to activate a single kind of neuron, at a precise location, with a single beam of light.
In an earlier incarnation, Boyden’s device looked like a needle-thin probe with light-emitting ports along its length; this setup allowed scientists to manipulate neurons along a single line. The new tool contains up to a hundred of these probes in a square grid, which makes the device look like a series of fine-toothed combs laid next to each other with their teeth pointing in the same direction.
Each probe is just 150 microns across, a little thicker than a human hair, and thin enough so that the device can be implanted at any depth in the cortex without damaging it. The brain lacks pain receptors, so the implants do not cause any discomfort to the brain itself. As in the earlier model, several light-emitting ports are located along the length of each probe.
Scientists can illuminate and change the color of each light port independently from the others.
Adding a third dimension to the probe’s light-delivery capabilities has allowed researchers to make any pattern of light they want within the volume of a cubic centimeter of brain tissue, using a few hundred independently controllable illumination points.
“It’s turning out to be a very powerful and convenient tool,” said MIT professor of electrical engineering Clifton Fonstad, co-lead author of the paper.
Teams from around the world are currently using the technology developed by Boyden’s group to study some of the most profound questions neuroscience tries to answer, such as how memory works, the connections between memory and emotion, and the difference between being awake and being asleep.
A better understanding of the brain may lead to another benefit of this technology: therapy.
If a particular type of cell malfunctions in a particular disease, scientists may be able to use a modified 3-D array as a neural prosthesis that could help to treat neurological conditions.
Using light to stop overactive cells from firing might alleviate the uncontrollable muscle action of Parkinson’s disease. Cells that cause seizures in the brain could be quieted optically without the side effects of anti-seizure medications. Implants that correct hearing deficiencies are also being explored with this technology.
Although the new device is effective in bringing light to the brain, other challenges remain before optogenetics can be used for medical therapy, Boyden said.
Scientists do not yet know for certain whether the body will detect the opsin proteins as foreign molecules and reject them. Gene therapy will also have to prove itself if neurons are to be sensitized with opsin effectively.
“It’s a long road,” Boyden admitted.
The researchers described their device in a paper published today in the Optical Society’s (OSA) journal Optics Letters.