"We now know that the mammalian brain can launch molecular machinery that promotes resilience to stress, and we know what several major components are. This is an excellent indicator that there are similar mechanisms in the human brain," said NIMH Director Thomas R. Insel, MD.2
Looking at a specific part of the brain, the researchers found differences in the rate of impulse-firing by cells that make the chemical messenger dopamine. Vulnerable mice had excessive rates of impulse-firing during stressful situations. But adaptive mice maintained normal rates of firing because of a protective mechanism — a boost in activity of channels that allow the mineral potassium to flow into the cells, dampening their firing rates.
Higher rates of impulse-firing in the vulnerable mice led to more activity of a protein called BDNF, which had been linked to vulnerability in previous studies by the same researchers. With their comparatively lower rates of impulse-firing, the resistant mice did not have this increase in BDNF activity, another factor that contributed to resistance.
The scientists found that these mechanisms occurred in the reward area of the brain, which promotes repetition of acts that ensure survival. The areas involved were the VTA (ventral tegmental area) and the NAc (nucleus accumbens).
In a series of experiments, the scientists extended their findings to provide a progressively larger picture of the vulnerability and resistance mechanisms. They used a variety of approaches to test the findings, strengthening their validity.
"The extensiveness and thoroughness of their research enabled these investigators to make a very strong case for their hypothesis," Insel said.2
For example, the researchers showed that the excess BDNF protein in vulnerable mice originated in the VTA, rather than in the NAc. Chemical signals the protein sent from the VTA to the NAc played an essential role in making the mice vulnerable. Blocking the signals with experimental compounds turned vulnerable mice into resistant mice.
