Controlling and Lighting Up Brain Activity
One of the most revolutionary advances in the field of the past decade is a technique called optogenetics. It involves delivering genes to produce the protein opsin, which is related to a protein found in the retina that can detect light. By inserting opsin genes into specific types of neurons, researchers can precisely control activity in the brain by activating or deactivating targeted cells.
“Once we can control these neurons, we can activate or inactivate them to study what they do,” Sommer explains.
A related technique uses the same principles but inserts genes for designer receptors that are not naturally found in neurons. With this chemogenetic approach, molecules instead of light can be used to turn on and off neurons of precisely selected types. Whereas optogenetics works at superfast time scales, chemogenetics has the staying power to influence circuits over many minutes, which can be crucial for studying impacts on behavior.
Both of these specialized genes, coding for light sensors or designer receptors, can be introduced to the brain using modified viruses. These viruses have been programmed so they don’t replicate like standard viruses, but instead act like a delivery system. While this method has been highly effective in small animal models, it doesn’t work as well in the primate brain, which is about 200 times larger than the rodent brain and equipped with stronger defenses.
“Primates have a much more sophisticated immune system, which can more effectively destroy these viral delivery methods,” says Sommer. “If we are going to make any advances in studying the primate brain, we need to tackle this problem head-on, so my lab is collaborating with experts in virology and human gene therapy to develop more effective delivery vectors.”
Since starting the project four years ago, the team—led by postdoctoral fellow Martin Bohlen—is optimizing several viruses identified as promising delivery candidates. They are also developing immunosuppressive approaches that help mitigate the primate immune response. Establishing this groundwork is a critical step for making optogenetics and chemogenetics routine methods for primate neuroscience, which could then translate directly to new clinical therapies.