Stress is generally not a good thing. Most of us who live stressful lives (which, I suppose, would be all of us), are well aware of this. We try to reduce our stress, or even stress about how stressed we are. Traumatic stress increases the risk for all sorts of psychiatric disorders, including major depressive disorder, anxiety, and post traumatic stress disorder. But not all stresses are created equal, even the traumatic ones. And it turns out that it's not the stress itself that is's whether or not you have any control over it.

Varela et al. “Control over Stress, But Not Stress Per Se Increases Prefrontal Cortical Pyramidal Neuron Excitability” Journal of Neuroscience, 2012.

A stress that you can control is a very different one from a stress that you can’t. I usually think of a stress you cannot control as something like the illness of a family member, as compared to a stress you can control, say, the stress involved in training for and running a marathon (which is definitely a physical stressor). These are both stresses, but they aren’t alike. While the stress that you cannot control is often a very traumatic experience, and can predispose people to psychiatric disorders, a controllable stress is actually a good event. Not only does it blunt the impact of the stressor itself, it can be protective against the detriments of future uncontrolled stresses. Scientists call this “behavioral immunization” against future stress.

Behavioral immunization involves the recruitment of very specific brain regions, especially the medial prefrontal cortex of the brain.

After exposure to a controllable stress, there is increased activity in the medial prefrontal cortex, and it is thought that the increase in activity is important for the development of behavioral immunization. If you stop this increased activity from taking place during controllable stress, you can prevent behavioral immunization.

But the medial prefrontal cortex is not a single area. Instead, it is divided into the infralimbic cortex and the prelimbic cortex. Each of these areas plays a different role in emotionally processing and expression. But which one is involved in behavioral immunization?

To look at this, the authors of this study exposed rats to either escapable or inescapable stress. The rats are put in a chamber where they will receive a tail shock at random intervals. Half of them have no choice, but the other half have a little wheel. When they turn the wheel, the shock will stop, allowing them to escape the stress. They also had another groups of control rats that never got the shock at all.

After exposure to escapable or inescapable stress, the authors used electrophysiology to see how the neurons in the prelimbic cortex responded. Electrophysiology is a very widely used technique in neuroscience, and is a fascinating way to peer inside the electrical life of a cell. You take a cell (this study worked in slices, but you can also do it in the whole animals), and very, very carefully impale it with a small glass electrode. The electrode is hollow with a little hole in the tip, and by suctioning very carefully, you can merge your electrode in with the membrane of your cell. From there, you have access to all the electrical impulses that run across the cell membrane. You can then take a stimulating electrode, stimulate somewhere else, and watch the cell respond. How much and in what way the cell responds tells you not only what kind of cell it is, but how responsive it is following something like inescapable stress.

The authors found that rats exposed to escapable stress had the makings of behavioral immunization beginning in the prelimbic cortex. When rats were allowed to escape the stress, after the stress the neurons in the prelimbic cortex showed increased electrical activity. The neurons were more excitable. This is a state that has been linked to the development of behavioral immunization. In contrast, the animals that could not escape the stress showed no changes when compared to control, nonstressed rats. This would mean that the rats exposed to escapable stress would end up with more responsive neurons in the prelimbic cortex, which might help them adapt to further stressors.

The medial prefrontal cortex in general has a lot of potential in stress research. Just exciting this area is enough to create resilience to stress in animals. It appears that this effect may be particularly important in the prelimbic area. And this could have potential for work in human stress. Not all stresses are necessarily entirely bad. And work in this area could give us important information on ways to help people who are, or have been, exposed to trauma. If we could produce a behavioral immunization beforehand, for example, we may be able to help people who are likely to go into combat, or if we can target this area to promote stress resilience, we could help those who have already been exposed to traumatic stress.

Varela JA, Wang J, Christianson JP, Maier SF, & Cooper DC (2012). Control over Stress, But Not Stress Per Se Increases Prefrontal Cortical Pyramidal Neuron Excitability. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (37), 12848-53 PMID: 22973008