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A microscopic light-emitting diode device that controls the activity of neurons has given researchers wireless control over animal behavior. The tiny device, tested in mice, causes less damage than other methods used to deliver light into the brain, report researchers in Thursday’s issue of Science, and it does not tether mice to a light source, enabling scientists to study behaviors more naturally than is normally possible.

Many groups of neuroscientists have turned to light-based control of neurons to study the neuronal basis of behavior. To control the brain cells, researchers use optogenetics, a method for genetically modifying neurons that allows them to be activated or silenced with flashes of light (see “Brain Control”).

Optogenetics has been used to study sleep, depression, and epilepsy (see “Decoding the Brain with Light” and “Flipping on the Lights to Halt Seizures”) and it may one day even make it into patients (for example, see “Company Aims to Cure Blindness with Optogenetics”). Many of these studies have used optic fibers or relatively large LEDs to control brain activity, which requires the animal in the study to be tethered to a laser or power source.

When Michael Bruchas, a neuroscientist at Washington University in St. Louis, began using optogenetics to study stress-related behaviors in mice, he was frustrated by the limits that tethered devices put on studies involving complex environments or multiple mice. So he teamed up with John Rogers, a materials scientist at the University of Illinois at Urbana-Champaign, and others, to develop a “device that has a very small ultrathin profile, is noninvasive, and can be controlled wirelessly,” says Bruchas. “It gives you more power to study different circuits wired for specific behaviors. Animals can be in their home cage or interacting with another animal or running on a wheel.”

The flexible device is roughly one-fifth the width of a human hair and can be implanted deep inside the brain with the help of a microneedle. A biodegradable adhesive holds the micro-LED implant onto the needle, but that grip is lost as the silk-based adhesive dissolves within a matter of minutes. The device is then left in the brain when the needle is removed. A wire even thinner than the device connects the micro-LED to electronics, including a wireless transmitter, that sit on top of the mouse’s head. Altogether, the setup weighs less than one gram, says Bruchas (a mouse weighs about 30 grams).

The researchers used the implants to control the activity of reward-circuit neurons in mice. Mice with modified neurons were given free range of a Y-shaped enclosure in which some paths ended with a small hole. If the mice poked their nose in that hole, the LED implant would activate neurons in their reward circuit. The mice learned to “self-stimulate,” says co-first author Jordan McCall of Washington University School of Medicine.

After several weeks in the brain, the micro LED devices resulted in fewer lesions, fewer neurons dying, and less immune response than conventional methods caused over the same time frame. And after six months in the brain, the miniaturized device still worked, says McCall.

Furthermore, because the four LEDs used are much smaller than an optical fiber, the researchers could precisely activate only a handful of neurons in the rodent brains. “If you want to control a large volume of tissue, then fiber-coupled LEDs might be more efficient, but if you want to do precision targeting of just a few cells, what they’ve done is a great improvement,” says Christian Wentz, founder of Kendall Research, a startup also developing wireless optogenetic devices (see “Startup Makes ‘Wireless Router for the Brain’”).

The miniscule optogenetics device also contains sensors for light, heat, and electrical activity, all of which allowed the researchers to monitor how well the device was working, and to activate neurons without overheating the surrounding brain.

This kind of device could eventually be used to control brain activity in an automated fashion: communicating with neurons though flashes of light in response to chemical, temperature, or electrical changes in the brain.The ability to integrate sensors as well as LEDs could enable ‘closed-loop’ control of brain functions, which could be of use for applications in which information must be both observed and read,” says MIT’s Ed Boyden, one of the co-inventors of optogenetics.

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Credit: John Rogers and Michael Bruchas

Tagged: Biomedicine, optogenetics, LEDs, John Rogers, microfabrication, Ed Boyden, behavior

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