Neuroscientists at the Massachusetts Institute of Technology have developed a powerful new class of tools to reversibly可逆地 shut down brain activity using different colors of light. When targeted to specific neurons神经原, they could potentially lead to new treatments for abnormal brain activity associated with disorders1 including chronic慢性的,长期的 pain, epilepsy癫痫, brain injury and Parkinson's disease. Such disorders could best be treated by silencing, rather than stimulating3 abnormal brain activity. These new tools, or 'super silencers,' exert运用,发挥 exquisite优美的,细致的 control over the timing5 in which overactive过于活跃的 neural6 circuits are shut down --an effect that is not possible with existing drugs or other conventional therapies.
The National Science Foundation's division of mathematical sciences supports the research through a grant to the Cognitive7 Rhythms Collaborative, which is comprised of four research groups in the Boston area focused on questions in neuroscience神经系统学. The collaborative brings together researchers with expertise8专门技术,专门知识 ranging from experimental design to mathematical modeling. The research paper, "High-Performance Genetically-Targetable Optical Neural Silencing by Light-Driven Proton Pumps," appears in the Jan. 7 issue of the journal Nature.
"Silencing different sets of neurons with different colors of light allows us to understand how they work together to implement9 brain functions," explains Ed Boyden, senior author of the study. "Using these new tools, we can look at two neural pathways and study how they compute10 together," he says.
The tools promise to help researchers understand how to control neural circuits, leading to new understandings and treatments for brain disorders. Boyden, the Benesse Career Development Professor in the MIT Media Lab and an associate member of the McGovern Institute for Brain Research at MIT, calls brain disorders "some of the biggest unmet未满足的,未应付的 medical needs in the world."
Boyden's 'super silencers' derive11 from来自,得自 two genes12 found in different natural organisms such as bacteria and fungi真菌. These genes, referred to as Arch and Mac, are light-activated14 proteins that help the organisms make energy. When Arch and Mac are placed within neurons, researchers can inhibit15 their activity by shining light on them. Light activates16 the proteins, which lowers the voltage in the neurons and safely and effectively prevents them from firing. Arch is specifically sensitive to yellow light, while Mac is activated with blue light.
"In this way the brain can be programmed with different colors of light to study and possibly correct the corrupted17 neural神经的 computations that lead to disease," explains co-author Brian Chow, postdoctoral associate in Boyden's lab.
"Multicolor silencing dramatically increases the complexity18 with which you can study neural circuits神经回路," says co-author Xue Han, another postdoctoral researcher in Boyden's lab. "We will use these tools to parse19解析,理解 out the neural mechanisms20 of cognition认知."
Determining whether Arch and Mac are safe and effective in monkeys will be a critical next step towards the potential use of these optical silencing tools in humans. Boyden plans to use these 'super silencers' to examine the neural circuits神经回路 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.