Mouse experiments
offer insights, potential for new treatment strategies in humans
Two research teams have
figured out how to flip a switch in the brain circuits of mice that compels the
animals to groom themselves with their paws over and over.
The findings may
yield new strategies for reducing compulsive behavior such as repetitive hand
washing in humans who have obsessive-compulsive disorder and other diseases
marked by the trait such as autism and Tourette syndrome.
In one set of
experiments, researchers stimulated a particular neural pathway, generating
repetitive, excessive grooming in the mice. A second set of experiments with
mutant mice used the same pathway to eliminate the compulsive behavior. The
studies are published in the June 7 Science.
“In tandem, this is really a leap forward towards a refined understanding of the circuitry underlying these behaviors,” says psychiatrist Scott Rauch of McLean Hospital in Belmont, Mass.
An uptick in the
activity of two brain regions, the orbitofrontal cortex and ventromedial striatum,
had previously been identified in brain scanning experiments of people with
obsessive-compulsive disorder, which afflicts roughly 1 percent of the
population worldwide.
People with OCD have obsessive thoughts, such as worrying
that they forgot to turn off the stove, and then perform compulsive behaviors
in response, such as repeatedly checking the stove’s dials.
While those general
brain regions had been implicated, there’s little understanding of the causal
relationship between faulty brain wiring and the behaviors. So scientists led
by psychiatric neuroscientist Susanne Ahmari of Columbia University targeted
the implicated brain regions in living mice by injecting a virus into nerves
that run between them, enabling the nerves to respond to light.
After five minutes of
laser stimulation per day for about five days, the mice started compulsively
grooming. Surprisingly, the repetitive grooming continued for two weeks after
the stimulation stopped.
“This is really
important,” says Ahmari. “If we can figure out triggers that make the brain
more likely to be hyperactive, we may be able to prevent OCD before it starts.”
Such triggers might include genetic factors predisposing the nerves to
hyperactivity or environmental factors such as traumatic events or stress, she
speculates.
Another study led by
Eric Burguière and Ann Graybiel at MIT examined the same circuitry in normal
mice and in mice genetically engineered to compulsively groom. Both sets of
mice were trained to groom when they heard a tone followed by a drop of water
on the nose. The water drop isn’t pleasant; the mice soon learned to groom when
they just heard the tone.
While the normal mice waited to groom until just
before the drop hit, the mutant mice groomed right at the tone.
“They get hooked on this
external stimulus,” says Graybiel. “It’s compulsive.”
But when the scientists
stimulated the designated brain circuit with light, it stopped the compulsive
behavior in the mutant mice and they groomed as the normal mice did.
Rauch notes that the two
studies not only offer promise for future research and treatments in humans,
but they validate that experiments with mice are a legitimate means of
investigating compulsive disorders.
