Laser Probes for Brain Experiments

19 May 2009—Understanding how the brain works typically involves sticking sharp metal electrodes into an animal’s brain and zapping its neurons with electricity. But researchers at Case Western Reserve University, in Cleveland, are working on what could be a more benign, efficient, and effective way to study brain circuits: using light.

The researchers have created a new kind of brain probe by coating the inside of a tiny hollow glass needle with nanoparticles of lead selenide, a semiconductor commonly used in infrared detectors. They insert the needle tips into slices of rat brains and shine infrared light from an 830-nanometer-wavelength titanium-sapphire laser on the probes. The nanoparticles absorb photons and generate an electric field that stimulates neurons, whose signals are recorded using another electrode placed next to them.

Metal electrodes activate only brain cells that are in a tight cluster around the electrodes, which is not what happens when you naturally stimulate your gray matter. ”When you smell a rose, you’re activating many, many brain cells, but they’re dispersed all over your olfactory system,” says Ben Strowbridge, a Case Western neuroscience professor who took part in the research. ”Our technique can get much closer to activating lots of different areas instead of activating many axons that are close together,” he says.

Ordinary electrodes can damage tissue, and they need wires to connect to power sources outside the brain. The light probes, on the other hand, could be made with thin, flexible optical fibers, tiny polymer microcapsules, or nanoparticle-coated flexible patches, says Clemens Burda, a Case Western chemistry professor who collaborated with Strowbridge. Once the probes are embedded in a certain part of the brain, you could wirelessly trigger neurons by scanning a laser beam on that area. (The near-infrared light used in the experiments is good at penetrating brain tissue.)

Beyond their use in neuroscience research, the photoelectrodes could also play a role in medicine. ”If one has a spinal cord lesion or a brain defect, we could excite the remaining brain cells in a biologically realistic way to restore function,” says Strowbridge.

Activating neurons with light instead of electricity isn’t a new idea, but the Case Western researchers are the first to use real brain tissue instead of neuron cultures, says Spencer Smith, a neuroengineer at the University College London. Other groups have grown neurons on top of thin silicon films connected to electrodes. The setup uses photoconductivity: Shining light on a patch of the film increases its conductivity, increasing current flow and triggering neurons on that patch.

Michael Colicos, a physiology and biophysics professor at the University of Calgary, in Canada, has worked on the photoconductive approach but sees promise in the Case Western technology. ”The advantage of the new technique is that you don’t need the current pulse from the material,” he says. ”The fact that you can liberate yourself from having to be directly electrically coupled with the electrode is a big step forward.”

Colicos finds the trick of coating the inside of the glass tip innovative, since the nanoparticles don’t touch the brain cells directly, reducing toxicity concerns. Strowbridge says his team did not see any evidence of damage to neurons over a few hours of testing with the electrodes nestled right next to the neurons. But they still need to do extensive toxicity studies.

There’s a ways to go before the researchers will be able to implant and control the circuits in a living brain. For now, they plan to make a lead selenide–coated glass surface and test brain slices placed on top. ”From that we can create flexible substrates that we can place right over the surface of the brain,” Strowbridge says. ”We’re certainly not there yet, but that’s where the technology is headed.”