This is a resubmission of an application for a FIRST Award. The applicant has recently begun to extend an extensive animal literature regarding the neurobiology of emotional memory storage to humans. The experiments to date confirm in human subjects the theory, anchored in animal studies that enhanced long-term memory for emotionally arousing events depends on the activity of, at minimum, two key nervous system elements: 1) endogenous stress hormones and 2) the Amygdaloid Complex (AC). The experiments proposed here are designed to build upon the initial results. Three general categories of experiments are proposed. The first are experiments involving stimulation of catecholamine receptors and long-term memory. These experiments will test in humans a critical prediction from the animal literature regarding neural mechanisms of emotional memory in humans, namely, that appropriate stimulation of catecholamine receptors enhances long-term memory formation. The second category of experiments involves blockade of catecholamine receptors. These experiments are designed to more fully investigate the applicants finding that beta-adrenergic receptor blockade selectively impairs emotional memory. Finally, PET scanning will be used to confirm and extend the applicants finding of a correlation between activity of the AC and long-term emotional memory. PET scanning will also be combined with beta adrenergic blockade to study the interaction between the AC and catecholamine receptors in emotional memory. Collectively, the proposed experiments will help provide a more detailed account of neurobiological mechanisms of emotional memory storage in humans. In so doing, they should also help bridge the gap between our understanding of the normal brain mechanisms subserving memory for emotionally negative events, and our understanding of how these mechanisms may underlie disorders associated with traumatic negative events, such as Post Traumatic Stress Disorder.
