Treating Depression by Fine-Tuning Motivation in the Brain

A group of neuroscientists has found brain cells that control the
motivation of mice to perform tasks for rewards. When these cells are
activated, mice work harder and avoid becoming addicted to rewards. The
discovery could lead to new treatments for mental illnesses such as
depression that affect motivation.

*Neuroscientists have discovered a set of brain cells that influence the
motivation of mice to perform tasks for rewards. Increasing the cells’
activity makes a mouse work harder or more vigorously. The neurons come
with a feature that prevents the mouse from overdoing it and becoming
addicted to the reward. The findings reveal new possible therapeutic
strategies for treating mental illnesses like depression that impair
motivation.*

A characteristic of depression is a lack of motivation. Cold Spring Harbor
Laboratory (CSHL) Professor Bo Li, in collaboration with CSHL Adjunct
Professor Z. Josh Huang, discovered a group of neurons in the mouse brain
that influences the animal’s motivation to perform tasks for rewards.
Dialing up the activity of these neurons makes a mouse work faster or more
vigorously—up to a point. These neurons have a feature that prevents the
mouse from becoming addicted to the reward. The findings may point to new
therapeutic strategies for treating mental illnesses like depression that
affect motivation in humans.

The anterior insular cortex is a region of the brain that plays a critical
role in motivation. A set of neurons that activate a gene called *Fezf2*(
*Fezf2* neurons) in this area are active when mice are doing both physical
and cognitive tasks. Li and his lab hypothesized that these neurons do not
affect the mouse’s ability to do the task; rather, the brain cells
influence the mouse’s motivational drive.

Cold Spring Harbor Laboratory Professor Bo Li discovered a cluster of
neurons in the mouse brain that influence motivation. These cells activate
a gene called Fezf2 and are connected to and activate other neurons, which
are stained green in this image of a mouse brain. Credit: Li lab/CSHL, 2021

Mice were trained to lick a water bottle spout to receive a small sugar
reward. When researchers dialed up the activity of these *Fezf2* neurons,
mice would lick more vigorously. If the neuron activity was dialed down,
the mice would lick more slowly. The researchers saw a similar result in
another experiment in which the mice ran on a wheel to receive a reward.
The mice ran faster if the *Fezf2* neurons were stimulated. The same effect
occurred with other tasks.

Li and his team were surprised to discover a feature that prevents the mice
from becoming addicted to the tasks and their rewards. When mice drank
their fill of sugar water and were satiated, they would not lick or run
faster to get more sugar, even if the researchers dialed up the activity of

Bo Li, Professor, Ph.D., The University of British Columbia, 2003

Finding a way to fine-tune the human equivalent of these neurons might help
people struggling with motivation due to mental illnesses like depression.
Li says, “We want to selectively increase the motivation of the person so
that they can do the things that they need to do, but we don’t want to
create addictive drugs.”

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