Scientists at Stanford’s lab of Dr. Karl Deisseroth developed a novel technology that not only sheds new light on pathophysiology of Parkinson’s, but may even one day become a therapeutic modality for this disease. The research involves deep brain stimulation of the brain’s subthalamic nucleus region, which is already a common therapy for people suffering from Parkinson’s. Until now the mechanism by which electrical signals lead to an improvement in symptoms has been a mystery in the medical community. So to understand what’s going on, Dr. Deisseroth et. al. developed thin, flexible fiber-optic cables, and compatible rodents with light sensitive neurons. By stimulating cells within the subthalamic nucleus using a fiber optic probe the researchers found little effect. Yet, when the axons that lead from the region to the outer regions of the brain were illuminated, the mice lost the symptoms of Parkinson’s.
To perform the research, Deisseroth’s team, which included students and faculty from bioengineering, neuroscience and neurosurgery, used a technique his lab has pioneered called “optogenetics.” They genetically engineered specific types of cells, or neurons, in the subthalamic nucleus regions of different rodents to become controllable with light. A blue-colored laser pulse makes the neurons more active, while a yellow laser light suppresses activity.
“Using the technology allowed us to separate the different circuit elements by placing them under optical control,” Deisseroth said. “It allowed us to systematically move through the circuit, turning on or off different elements and finding out which modifications of the circuit corrected the symptoms.”
This result also required a complementary method invented in the Deisseroth lab, namely delivering light via a thin, flexible fiber-optic cable deep into the brain of the animals, so that they can move and behave freely during the experiment.
The team tried every kind of neuron they could think of within the brain region itself, and found no effect. Out of persistence and desperation, like a person who has searched the whole house for the keys and finally finds them in the doorknob, the team decided to investigate the incoming axons. In rodents with cells that had been made light-sensitive, the researchers found dramatic results both with high-frequency and low-frequency pulses.
“The [high-frequency stimulation] effects were not subtle,” the researchers wrote in the Science Express paper. “In nearly every case these severely Parkinsonian animals were restored to behavior indistinguishable from normal, and in every case the therapeutic effect immediately and fully reversed…upon discontinuation of the light pulse.”
Low-frequency stimulation, meanwhile, caused the Parkinson’s symptoms to become worse.
Here’s more details about optogenetics from the New Scientist:
Called optogenetics, the technology relies on light-sensitive proteins called channel rhodopsins that are normally produced by algae.
Deisseroth’s team previously found that inserting a channel rhodopsin into neurons allows them to be activated with blue light. Similarly, an engineered protein called halo-rhodopsin can silence brain cells when flashed with yellow light.
The proteins do this by pumping charged ions into or out of cells in response to light, creating the electrical potential that is the native language of neurons.
Full story: Stanford study improves insights into Parkinson’s disease and possible treatments
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