Stress, Overactive Neurons, and Depression


The same level of stress motivates some individuals, spurring them into action, yet is overwhelming and paralyzing for others.

In Cold Springs Harbor Laboratory, scientists have gained insight into why this occurs—why stress affects people’s behavior differently. They have identified a group of neurons that, when over-activated by stress, trigger depressive behaviors.

This study, completed with the participation of laboratory mice, also helps explain why deep brain stimulation - electrically suppressing neuron activity in specific brain areas - relieves symptoms of depression in some people.

The Problem Neurons

The neurons studied at Cold Springs Harbor Labs (CSHL) are in the brain’s medial prefrontal cortex (mPFC). The mPFC is involved in emotion and behavior by associating our actions and feelings. For years, brain scans showed the mPFC to be hyperactive in depressed people but, it was impossible to tell whether this excess activity caused depression or was a side effect.

By genetically marking certain neurons, the CSHL research team found that:

  1. Stress caused the mPFC neurons to become excitable or overactive in depressed mice.
  2. Stress weakened the same mPFC neurons in non-depressed, resilient mice.

These results suggested to the investigators that the hyperactive neurons were a cause of depression, but they still were not sure.

Proving Cause

To investigate further, the researchers took some of the resilient mice and artificially excited the neurons in their mPFC through a process called chemical genetics. The once resilient mice, now with overactive neurons, began showing all the typical behaviors related to depression such as helplessness.

The findings suggest that deep brain stimulation may relieve depression by weakening overactive neurons that trigger depressive behaviors.

Next on the CSHL agenda is investigating why mPFC neurons become hyperactive in some individuals and not others.

“These active neurons are surrounded by inhibitory neurons,” said researcher Dr. Bo Li. “Are the inhibitory neurons failing? Or are the active neurons somehow able to bypass their controls? These are some of the many open questions we are pursuing to understand how depression develops.”

Source: CSH Laboratories
Photo credit: Andrew Mason


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