Compiled by BioPhotonics staff
CHAPEL HILL, N.C. – Scientists have used optogenetics to control reward-seeking behaviors such
as drug addiction in rodents, demonstrating the roles of specific connections in
the brain that control behavior.
Through combining genetic engineering and laser technology, scientists
at the University of North Carolina tweaked the microcircuitry of the brain so that
they could assess how those changes affect behavior. Their findings, which appeared
in the June 29 issue of Nature (doi: 10.1038/nature 10194), suggest that therapeutics
that target the path between two critical brain regions – the amygdala and
the nucleus accumbens, the regions that are associated with reward – could
act as treatments for neuropsychiatric diseases and addiction.
Nerve cells in the nucleus accumbens (red) receive input from amygdala fibers (green). Optogenetic stimulation of these nerve fibers produces a rewarding effect in mice. Courtesy
of Stuber Lab, UNC-Chapel Hill.
These regions are important for assessing clinical disorders,
but until now there were no proper tools to directly study the connections between
Using the new technique, scientists transferred light-sensitive
proteins called “opsins” – derived from algae or bacteria that
need light to grow – into mammalian brain cells they wished to study. Shining
a laser beam directly onto the genetically manipulated brain cells, they could either
excite or block the activity with millisecond precision.
Initial experiments targeted the nerve cells that connect the
amygdala and the nucleus accumbens. Using light to activate the connection between
the regions, the scientists “rewarded” the mice with laser stimulations
for performing mundane tasks, such as poking their nose into a hole in their cage.
The mice treated with opsins quickly learned how to obtain stimulation of the neural
pathway, while the genetically untouched mice in their experiment never caught on
to the task.
To study whether this brain wiring plays a role in more natural
behavioral processes, the scientists trained the mice to associate a cue –
in this case, a light bulb turning on in the cage – with a reward of sugar
water. This time, the opsin that was transferred into the brains of the mice was
one that shut down the activity of neural connections in response to light. While
delivering the cue to the control mice, they blocked the neuronal activity in the
genetically altered mice, and they observed that the control mice responded quickly
to the cue by licking the sugar-producing vessel, while the treated mice did not
exhibit the same response.
The researchers are exploring how changes to this segment of brain
wiring could render animals either sensitized or oblivious to rewards. Proving a
useful tool for studying brain function, the technique could one day provide an
alternative to electrical stimulation or pharmacotherapy for neuropsychiatric illnesses
like Parkinson’s disease.