Parkinson’s disease is often treated with deep brain
stimulation (DBS), which delivers electrical pulses to a deep-seated cluster of
neurons called the subthalamic nucleus. But while the technique is successful
in many patients, scientists have struggled to understand its mechanism.
“What’s been mysterious is we don’t know how those
stimulation treatments really work,” says Karl Deisseroth, a
bioengineer and psychiatrist at Stanford University and senior researcher on a
new project that sheds light–literally–on how DBS affects the Parkinsonian
brain.
Advertisement
Deisseroth and his colleagues engineered cells in the
subthalamic nucleus of mice with Parkinson’s to express proteins derived from
light-sensing bacteria. One protein triggers cells to fire in response to blue
light, while another quiets cells’ electrical activity in response to yellow
light. The researchers systematically marched through the circuit targeted by
DBS, piping in light through a fiber-optic cable to probe each cell type in
turn.
This story is only available to subscribers.
Don’t settle for half the story.
Get paywall-free access to technology news for the here and now.
“What we found was quite surprising,” says Deisseroth. None
of the cell types in the subthalamic nucleus, when stimulated or calmed by light,
had any effect on the mice’s symptoms. But when light was used to activate the
wire-like axons projecting to the subthalamic nucleus from other parts of the
brain, the mice’s symptoms were completely reversed. The results appeared
online yesterday in the advance online edition of Science.
“That showed that a big feature of disease pathology may not
always be misfiring of cells within a structure,” says Deisseroth, “but more
the flow of information between structures.”
The researchers hope that by tracing the axons back to their
source–nearer to the surface of the brain–they will uncover potential targets
for less invasive treatment of the disease. Deisseroth also believes that a newer incarnation
of his team’s light-based approach, which activates cells biochemically
rather than electrically, could reveal why some patients respond better than
others to the electrical activation DBS produces. “For some symptoms or some
disease states, biochemical modulation may be what should be the primary
target,” he says.