Appetitive and aversive state interactions in the central amygdala during learning and memory

Project Summary The exact nature of how positive and negative affective stimuli reciprocally interact within the brain to influence learning and memory is not well resolved. Understanding how positive affective states impact discriminatory threat learning, memory retention, and extinction has broad implications for the effectiveness of cognitive behavioral therapies. Based on its connectivity to brain regions involved in threat responding, threat generalization, the negative affect of pain, and salience detection, we hypothesize that the central nucleus of the amygdala (CeA) is a key site for the integration positive and negative affective state information that is important for the regulation of threat learning and the influences of affective state. Our preliminary results demonstrate that co-presentation of a conditioned stimulus associated with positive valence with a conditioned stimulus associated with a negative valence can prevent, reverse, or facilitate the extinction of a generalized threat memory. We further show that this effect is dependent on the activation of neurons in the ventral tegmental area and the modification of fear encoding neurons of the CeA by dopamine release. In this proposal, we seek to resolve how positive stimuli influence fear encoding and threat discrimination at the level of activation of specific neurotransmitter receptors in the CeA to facilitate discriminatory threat memories. We further seek to resolve how positive and negative affective stimuli are differentially encoded in the CeA and how these cell types can influence each other’s activity during positive and negative valence learning. Resolving the basic brain mechanisms that allow positive affective stimuli to influence threat memories has important implications for improving cognitive behavioral therapies in the treatment of generalized anxiety disorders.