The Basolateral Amygdala: The Core of a Network for Threat Conditioning, Extinction, and Second-Order Threat Conditioning

SIMPLE SUMMARY: Threat conditioning is a process by which animals learn about danger. As such, this process has been extensively studied as a model of how humans develop fears and anxiety, and their related disorders such as post-traumatic stress disorder (PTSD), which affects seven to eight percent of adults at some point in their life. Conversely, threat extinction is essentially the reverse of this process, by which animals adaptively learn that something is no longer dangerous. Threat extinction forms the basis of exposure therapy, a cornerstone in the treatment of such disorders, during which patients face their fears in order to overcome them. So-called higher-order forms of learning such as second-order threat conditioning add layers of complexity to threat conditioning and may thus more closely mimic processes underlying the development of such disorders. While the amygdala has long been thought to be at the center of such processes, being activated and suppressed during threat conditioning and extinction, respectively, in reality a complex network of structures governs these forms of learning. While such networks are not proposed to hold all the answers to our understanding of the development and treatment of such disorders, they are an important piece of the puzzle, and are thus reviewed here. Recent advances are presenting new areas of exploration into the brain-based mechanisms of such forms of learning and may ultimately inform the treatment of fear- and anxiety-related disorders. ABSTRACT: Threat conditioning, extinction, and second-order threat conditioning studied in animal models provide insight into the brain-based mechanisms of fear- and anxiety-related disorders and their treatment. Much attention has been paid to the role of the basolateral amygdala (BLA) in such processes, an overview of which is presented in this review. More recent evidence suggests that the BLA serves as the core of a greater network of structures in these forms of learning, including associative and sensory cortices. The BLA is importantly regulated by hippocampal and prefrontal inputs, as well as by the catecholaminergic neuromodulators, norepinephrine and dopamine, that may provide important prediction-error or learning signals for these forms of learning. The sensory cortices may be required for the long-term storage of threat memories. As such, future research may further investigate the potential of the sensory cortices for the long-term storage of extinction and second-order conditioning memories.