Gallo Researchers Use Pulses of Light to Change Mouse Minds
Source: UCSF press release
Date: August 19, 2012
A Gallo Center research team led by Linda Wilbrecht, PhD, has
demonstrated that complex decision-making in mice can be biased
with pulses of light. The pulses directly stimulate neural pathways
in the dorsal medial striatium, a brain region involved in
decision-making and addiction.
In a study published on August 19, 2012 in
Nature Neuroscience,
co-authors Lung-Hao Tai, PhD and Moses Lee trained mice to seek a
water reward by making one of two choices. The mice indicated their
decision by poking their noses into a central port, and then moving
either to the left or right to obtain the water. To make the task
challenging for the mice, water was delivered with only 75 percent
probability after a correct choice, and the side that delivered water
was switched after a block of seven to 23 trials on each side. Based
on these complicated rules, the mice had to remember where they had
been and what had happened in the prior two to three trials in order
to correctly predict which side to choose.
Once mice learned the task, the scientists sought to alter how
they weighed the evidence provided by their memory of past trials.
The researchers did this by altering activity in the dorsal striatum.
The team focused on two circuits—the dopamine D1 receptor expressing
“direct pathway,” which is thought to facilitate action, and the
dopamine D2 receptor expressing “indirect pathway,” which is thought
to inhibit competing actions. “Previous studies have shown that
increased activity in the dorsal striatum can be seen just prior to
a choice, suggesting that the decision process may, in part, be
controlled by this brain region,” said Wilbrecht. The researchers
used a technique called optogenetics to stimulate the D1 or D2 pathway
with a few short pulses of blue light during a half-second period just
before the mouse made the decision to go left or right. These few pulses
caused the striatal neurons to fire a few extra action potentials in
response to the light, adding to the activity of the brain as it made
a decision.
Wilbrecht and her team found that stimulating the D1 pathway biased
choices toward the side opposite that of the side of the brain being
stimulated, while stimulating the D2 pathway biased choices toward the
same side as that being stimulated. The size of the effect varied in
direct proportion to the rate and number of light pulses that were
administered—the more pulses, the larger the effect on choice.
“The point of trying to shift the mouse’s decision-making patterns
with light was to learn how the mouse brain uses activity in these
different cell types to weigh the value of competing choices,” explained
Wilbrecht. “These data help us understand how a decision to make an
action occurs at the cellular level.”
Discussing the experiment’s relevance to addiction research, Wilbrecht
noted, “Addiction is a disease of decision-making. We can’t really
understand addiction if we don’t understand how the brain assesses value
and makes decisions. If it’s broken, we need to know how it works in
order to fix it.”
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