The findings could lead to novel therapeutic ways for addressing mental disorders that affect motivation in humans, such as depression.

A lack of motivation is a symptom of depression. Professor Bo Li of Cold Spring Harbor Laboratory (CSHL) and CSHL Adjunct Professor Z. Josh Huang uncovered a set of neurons in the mouse brain that regulate the animal’s motivation to undertake tasks for rewards.

Increasing the activity of these neurons causes the mouse to work quicker or more vigorously—to a point. These neurons contain a characteristic that protects the mouse from developing an addiction to the reward.

The findings could lead to novel therapeutic ways for addressing mental diseases that impair motivation in humans, such as depression.

The anterior insular cortex is a brain area that is important for motivation. A group of neurons in this area that activate a gene called Fezf2 (Fezf2 neurons) are active when mice perform both physical and cognitive tasks. Li and his colleagues reasoned that these neurons do not alter the mouse’s ability to complete the task, but rather influence the mouse’s motivational drive.

Mice were taught to lick the spout of a water bottle in order to earn a little sugar reward. Mice licked more furiously when researchers increased the activity of these Fezf2 neurons. The mice would lick more slowly if the neuron activity was reduced. Another experiment in which mice ran on a wheel to obtain a reward yielded a similar effect, according to the researchers. When the Fezf2 neurons were activated, the mice ran faster. The same thing happened with other chores.

Li and his colleagues were taken aback when they discovered a feature that stops mice from becoming addicted to the tasks and their rewards. Even when mice were satiated after drinking their fill of sugar water, they did not lick or run faster to receive more sugar, even when the researchers increased the activity of the Fezf2 neurons.

Finding a means to fine-tune the human analogue of these neurons could benefit patients suffering from mental diseases such as depression.

Li said, “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.”

Source: 10.1016/j.cell.2021.11.019

Image Credit: Getty

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