To fear or not to fear: The role of the amygdala and prefrontal cortex in the regulation of fear.

摘要

The regulation of fear requires a delicate balance. With too little fear we become reckless, endangering ourselves and others. With too much fear we become paralyzed, unable to function. How is fear regulated so that we have just enough? The lateral amygdala (LA) is a key structure in fear learning. However, its role in the regulation of fear well after initial learning is largely unexamined. Part I of this work examined the effect of local infusions of muscimol and pentagastrin into the LA on fear elicited by a familiar auditory conditioned stimulus (CS). Muscimol infusions, which inhibit neural activity, attenuated the fear elicited by the CS. Pentagastrin infusions, which increase neural excitation, resulted in persistence of fear elicited by the CS. Thus, the LA plays an essential role in fear triggered by a familiar CS in addition to its established role in fear learning. In part II behavior and neural activity were simultaneously monitored in rats during fear elicited by the CS. We found that neural activity in LA encoded changes in fear: activity increased just before the onset of fear and decreased before the offset of fear. Part III examined the role of the medial prefrontal cortex (mPFC) in fear regulation. Physiologically, the mPFC and the LA are mutually inhibitory. The offset of fear was preceded by a change in neural activity in mPFC suggesting that neural activity in the mPFC inhibited fear. Taken together, these data support the idea that the amygdala and mPFC play contrasting roles in the neural circuit of fear regulation. Moreover, the data provide new insight into the computation performed by individual neurons in this circuit. These results are clinically relevant since treatment for post-traumatic stress often takes place long after the initial trauma.