Could Light Energy Be the Next Wave of Neuromodulation?

Last year, the Albert Lasker Basic Medical Research Award was given to the researchers who discovered light-sensitive microbial proteins known as opsins and developed a technique known as optogenetics that uses these proteins to manipulate neurons. This award, considered one of the most prestigious in medicine and a common gateway to a future Nobel prize, shows how far optogenetics has come in 15 years—from an unconventional neuroscience tool in studies of animals to one being considered as a neuromodulation therapy for people.

Unlike existing neuromodulation treatments such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), “optogenetics is a form of gene therapy that requires you to deliver specially modified genes to the target neurons,” explained Ed Boyden, Ph.D., the Y. Eva Tan Professor in Neurotechnology at the Massachusetts Institute of Technology. (Boyden collaborated with Lasker Prize winner Karl Deisseroth, M.D., Ph.D., a professor of psychiatry at Stanford University, to pioneer this technique.) These modified genes include microbial opsin DNA and thus produce proteins that respond to optical energy at specific wavelengths. When exposed to the right wavelength of light, the opsin proteins trigger an electrical signal that either stimulates or inhibits the activity of the neurons. Most opsins react to specific colors on the visible light spectrum, so optogenetics does not expose brain tissue to more damaging energy such as ultraviolet or X-ray light.

The desired genes are packed into vectors that contain bits of viral DNA; when injected into a part of the body, these vectors will enter a cell and splice the selected gene into the host chromosomes, just as many viruses do.

While the need for a genetic intermediary adds a layer of complexity to optogenetic stimulation relative to ECT and TMS, optogenetic stimulation provides one critical benefit: specificity.

“We can engineer the vectors we use for gene insertion to be highly selective,” said Meaghan Creed, Ph.D., an associate professor of anesthesiology at Washington University, who is exploring the potential of optogenetics in the management of pain and addiction. Researchers can make as few or as many neurons optically sensitive as they want, which enables precise control of neural activity. Clinically speaking, this precision means optogenetic stimulation could produce fewer side effects compared with ECT or TMS, which target a whole area of the brain, sometimes leading to unintended effects.