Shedding Light on Parkinson's Treatment

The use of light-activated proteins and fiberoptics helps Parkinsonian animals move more easily and quickly, and provides insight into brain circuits affected by the condition.

Using a technique to systematically characterize circuits in the brain implicated in Parkinson ’s disease, a Stanford University research team has identified a specific group of cells to target with deep brain stimulation (DBS), a surgical treatment for the condition. The technique is a vast improvement over previous methods because it allows researchers to precisely stimulate neurons and simultaneously measure the effect of treatment in animals with Parkinson's-like symptoms.

Termed optogenetics, the technology uses light-activated proteins, originally isolated from bacteria, in combination with genetic methods to control specific parts of the brain.

“The optogenetic approach allows us to control stimulation of specific cells in the brain on the appropriate timescale, much like a conductor directs specific sections of an orchestra at the appropriate time," said Karl Deisseroth, a research physician in Stanford’s bioengineering department and leader of the study.

Deisseroth's team found they could reduce disease symptoms by preferentially activating neurons that link to the subthalamic nucleus region of the brain. First, these specific cells were treated in a way that made them sensitive to stimulation by blue light, then the team implanted an optical fiber in the brain.

When researchers rapidly flashed blue light inside the animals' brains the disease symptoms improved. In contrast, treating with slower flashes of light made the symptoms worse, and targeting other kinds of cells had no effect at all, indicating both proper cell type and stimulation frequency are crucial components of effective treatment.

"We need to understand the players before we can develop effective treatment strategies," Deisseroth said.
Flashing blue light on portions of the same neurons found closer to the outer surface of the brain had an effect similar to treatment deep within the brain, raising the possibility that researchers may be able to develop treatments that are less invasive than current options.

Approved as a medical treatment in 1997, DBS remains controversial because it doesn't work on all patients. Used to treat Parkinson's disease, depression and movement disorders, DBS involves surgical implantation of a brain pacemaker, which sends electrical impulses into the brain. Researchers have been unable to understand precisely how DBS works because the electrical signal emitted by DBS devices interferes with the ability to observe brain activity.

The study, which was published in the April 17 issue of the journal Science, was supported by the National Science Foundation.

—By Lisa Van Pay/NSF.