Brain Activity Can Be Manipulated Using Multiple Colors of Light

Image courtesy of Brian Chow, Xue Han and Ed Boyden/MIT

Mouse neuron expressing the Arch gene.

By Ed Martinez

January 6, 2010

Neuroscientists have developed a powerful new class of tools to reversibly shut down brain activity using different colors of light. When targeted to specific brain neurons, these tools could potentially lead to new treatments for the abnormal brain activity associated with disorders such as chronic pain, epilepsy, brain injury, and Parkinson’s disease.

The tools work on the premise that such disorders might be best treated by silencing, rather than stimulating, brain activity. These “super silencers” exert exquisite control over the timing of the shutdown of overactive neural circuits—an effect that’s not possible with existing drugs or other conventional therapies.

Scientists loaded two genes knows as Arch and Mac into viruses that inserted their genetic cargo into mouse neurons. Optical fibers attached to lasers flashed light onto the neurons, and electrodes measured neural activity.

“Silencing different sets of neurons with different colors of light allows us to understand how they work together to implement brain functions,” explained Ed Boyden, senior MIT researcher of the study. “Using these new tools, we can look at two neural pathways and study how they compute together. These tools will help us understand how to control neural circuits, leading to new understandings and treatments for brain disorders—some of the biggest unmet medical needs in the world.”  

Boyden’s “super silencers” Arch and Mac genes can be found in various natural organisms such as bacteria and fungi. When neurons are engineered to express Arch and Mac genes, researchers can inhibit their activity by shining light on them. Light activates the proteins, which lowers the voltage in the neurons and safely and effectively prevents them from firing. Light can then bathe the entire brain and selectively affect only those neurons that are sensitive to specific colors of light. Neurons engineered to express Arch are specifically silenced by yellow light, while those expressing Mac are silenced by blue light.

Boyden’s team plans on using monkeys to determine if the genes are safe and effective. The next research study will be a critical next step toward the potential use of these optical silencing tools in humans. Boyden plans to use these “super silencers” to examine the neural circuits of cognition and emotion and to find targets in the brain that, when shut down, could relieve pain and treat epilepsy. His group continues to mine the natural world for new and even more powerful tools to manipulate brain cell activity–tools that, he hopes, will empower scientists to explore neural circuits in ways never before possible.