Behavioral control, the medial prefrontal cortex, and resilience

Maier, S.F., Amat, J., Baratta, M.V., Paul, E., & Watkins, L.R. (2006). Behavioral control, the medial prefrontal cortex, and resilience. Dialogues in Clinical Neuroscience, Vol. 8, No. 4, 397-406.

In a previous article reviewed, "Stressor controllability and learned helplessness: The roles of the dorsal raphe nucleus, serotonin, and corticotrophin-releasing factor", Maier et al showed that the degree of control an organism has over a stressor modulates the impact of this stressor. But how, exactly, controllability enters the equation neurobiologically was undiscussed. This article tackles that issue with some interesting conclusions drawn.

Although the dorsal raphe nucleus (DRN) plays a critical role in learned helplessness, it is unlikely that it is the brain structure responsible for detecting whether or not a stressor is under behavioral control or not. It has neither the processing power nor the appropriate inputs to make such an assessment. However, the ventral medial pre-frontal cortex (vmPFC) is thought to be that structure. Electrical stimulation of this area leads to inhibition of serotonin neurons in the DRN. And inactivating this region eliminates the differential effects of controllability -- that is, both inescapable and escapable shocks produce the same behavioral outcomes. Further, directly activating the vmPFC during inescapable and escapable shocks produces responses in the both groups equivalent to an escapable shock, eluding learned helplessness.

So-called 'immunization effects' are also interesting. Initial experiences with controllable shock appears to attenuate the typical behavioral response to a later exposure to uncontrollable shock. The article shows how the vmPFC becomes associated with the stressor during controllable shock trials and later becomes re-activating again during subsequent uncontrollable trials, thereby inhibiting the DRN.

Furthermore, this 'trained' vmPFC projects to other structures besides the DRN. One of particular importance is the amygdala which is known to play a critical role in classical fear conditioning. The article shows how the pathway from the vmPFC to the central nucleus of the amygdala (CE) can be used to inhibit CE function, thereby retarding fear conditioning. As has been shown, inescapable shock prior to fear conditioning exaggerates fear conditioning. But escapable shock, a stressful event in itself, before fear conditioning is actually shown to reduce the phenomena of fear (in comparison with never-before-shocked animals). The authors remarked, "We know of no other position that would predict, or even explain, how exposure to a highly stressful event could retard the later development of fear." In other words, repeated exposure to aversive stimuli hyper-sensitize the animal to fear. But, repeated exposure to aversive stimuli which the animal can exercise some control over actually helps to desensitize the animal to fear by involving the vmPFC. Still more encouraging, this mechanism of resilience may generalize broadly to quite different situations and circumstances.