Neurons in the medial prefrontal cortex (green, left image) become hyperactive in depressed mice. In the close-up (right panel), yellow indicates activation / Bo Li, Cold Spring Harbor Laboratory

Does stress motivate you, or does it defeat you? Researchers have identified a group of neurons in the brain that determine whether a mouse will learn to cope with stress or become depressed.

Up to 20 percent of us will struggle with depression at some point in our lives. While some become spurred on with renewed vigor, others other paralyzed by hopelessness. By identifying the neuronal basis of depression, the new mouse study could help us understand how depression develops.

Previous work with brain imaging have shown that the medial prefrontal cortex (mPFC) region becomes hyperactive in depressed people. This area of the brain helps control emotions and behavior, linking our feelings with our actions. A team led by Bo Li from Cold Spring Harbor Laboratory wanted to see if this increased activity actually causes depression, or if it’s just a byproduct of changes to neurons.

The researchers used a mouse model for depression known as “learned helplessness.” That’s when random foot shocks are delivered to see how the mice respond: Some mice will keep trying to avoid the unpredictable jolts, while others just give up, sit in a corner, and don’t try to move away. “This helpless behavior is quite similar to what clinicians see in depressed individuals -- an inability to take action to avoid or correct a difficult situation,” Li tells the Washington Post.

Having already marked specific neurons that respond to stress (pictured above), the team discovered that brain cells in the mPFC become highly excited in “depressed” mice; these same neurons are weakened in “resilient” mice who aren’t deterred by the repeated stressful shocks.

Next, using chemical genetics, they engineered mice to mimic the neuronal conditions found in depressed mice, artificially enhancing their mPFC activity. “The results were remarkable,” Li explains in a news release. “Once-strong and resilient mice became helpless, showing all of the classic signs of depression.”

The team is now exploring how neurons in the mPFC become hyperactive in depressed mice. They hope their work will better target deep brain stimulation, which suppresses the activity of specific neurons.

The work was published in the Journal of Neuroscience last month.

[CSHL via Washington Post]

Image: Bo Li, Cold Spring Harbor Laboratory