Acquisition and extinction of second-order context conditioned fear: Role of the amygdala

Second-order fear conditioning has been demonstrated in protocols using discrete and simple stimuli, and much is now known about its behavioral and neural characteristics. In contrast, the mechanisms of second-order conditioning to more complex stimuli, such as contexts, are unknown. To address this gap in our knowledge, we conducted a series of experiments to investigate the neural and behavioral characteristics of second-order context fear conditioning in rats. We found that rats acquire fear to a context in which a first-order conditioned stimulus is presented (Experiment 1); neuronal activity in the basolateral amygdala (BLA) is required for the acquisition (Experiment 2) and extinction (Experiment 3) of second-order context fear; second-order context fear can be reduced by extinction of its first-order conditioned stimulus associate (Experiment 4); and that second-order fear reduced in this way is restored when fear of the first-order conditioned stimulus spontaneously recovers or is reconditioned (Experiment 5). Thus, second-order context fear requires neuronal activity in the BLA, and once established, tracks the level of fear to its first-order conditioned stimulus-associate. These results are discussed with respect to the substrates of second-order fear conditioning in other protocols, and the role of the amygdala in different forms of conditioning.