Researchers Develop High-Precision Dual-Color Optogenetic Brain Probe

Optogenetics promises to manipulate brain circuitry by exciting or inhibiting neurons with different wavelengths of light. Until now, neural probes have largely been limited to single colors, only capable of either excitation or inhibition. Probes with close-packed dual-color light sources have proved to be elusive due to difficulties in integrating the necessary technology.

Now, researchers at the University of Massachusetts Amherst have developed a dual-color optogenetic neural probe. Unlike previous, single-color probes, which often control brain activity in only one direction — either excitation or inhibition — this new design can enhance and silence the electrical activities of the same neurons within specific cortical layers of the brain. It promises to aid the investigation of tightly packed neural microcircuits within the cortex and deep brain regions and, in the longer term, add to the functional mapping of the brain.

The tip of the optogenetic probe is about 0.2 millimeters wide and 0.05 millimeters thick. The device uses closely packed micro-LEDs to enable bidirectional in vivo optogenetic stimulation. Courtesy of the University of Massachusetts.

The researchers created a monolithic neural probe integrated with close-packed dual-color micro-LEDs and microelectrodes to enable in vivo optogenetic stimulation within two layers of the somatosensory cortex of a mouse. The team demonstrated the ability to excite and inhibit layer-specific brain dynamics.

Guangyu Xu, associate professor of electrical and computer engineering, appointee of the Dev and Linda Gupta Professorship at UMass Amherst and principal investigator of the study, hopes the device can ultimately help researchers identify the origin of brain diseases.

“We are able to send one of two colors of light (red or blue) to the brain to let neurons within each cortical layer become more active or more silent, as you can tell from electrical neural recording signals,” Xu said. “This capability, namely bidirectional optogenetic electrophysiology, will lend itself to high-resolution interrogation of the brain circuitry and shed light on animal disease models.”

According to Xu, bidirectional control is a crucial feature for advancing the understanding of diseases such as epilepsy and Parkinson’s disease. “For instance, with epilepsy, you may need to silence certain regions of the brain, not to activate them,” he said. “That requirement is one of our motivations in building such dual-color devices. The second color on the probe adds flexibility in optical control over the brain.”

Building such devices is not trivial, requiring different optoelectronic materials to be packed into a small footprint — less than a millimeter in size — with low crosstalk to each other. “We developed a high-yield integration approach in this work,” Xu said.

The work marks the first preliminary test of this technology, showcasing the power of the device to provide a high spatial resolution and bidirectional control of the brain in mice. “What we did on mice is turn on those blue or red LEDs to shut off or turn on the same local brain circuits,” he said. “And this spatial resolution comes down to specific cortical layers, which has been suggested in the recording traces.”

Xu anticipates that future research will extend to testing the device on other parts of the body, possibly outside the brain. The current research relates to Xu’s work on a project funded by the National Science Foundation to develop two high-density integrated optoelectronic arrays to probe muscle contraction and regeneration processes at subcellular resolution.

The research was published in Cell Reports Physical Science (www.doi.org/10.1016/j.xcrp.2023.101702).