http://www.medgadget.com/archives/2009/03/fiber_optics_activate_neurons_axons_to_answer_parkinsons_questions.html
Thursday, March 19, 2009
Fiber Optics Activate Neurons, Axons to Answer Parkinson's Questions
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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