Drug effects on learning and memory

University Of California-Irvine, Irvine CA

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Abstract

DESCRIPTION (provided by applicant): The overall long-term objective of this research program is to understand the neurobiological systems that mediate the influence of emotional arousal on long-term memory. The specific aims of the experiments are to determine: 1) whether noradrenergic activation of the basolateral amygdala (BLA), a brain region known to be activated by emotional arousal, is sufficient to enhance object- and context-recognition memory under training conditions that induce low levels of emotional arousal, 2) the interaction of the BLA with other brain regions, including the hippocampus and different cortical regions, in modulating the consolidation of object- and context-recognition memory, and 3) the influence of BLA activation on the consolidation of emotionally linked specific neuronal plasticity in the auditory cortex. The experiments will investigate the effects of posttraining intra-BLA infusions of norepinephrine or the 2-adrenoceptor antagonist propranolol on 24 hr retention of object- and context-recognition memory using training conditions that produce different levels of emotional arousal. Infusions of the muscarinic cholinergic agonist oxotremorine will be administered posttraining into the hippocampus, entorhinal cortex, insular cortex or rostral anterior cingulate cortex to investigate the differential effects of such cholinergic activation in enhancing memory for different types of information. Experiments will determine whether the effect, on memory, of activation of these other brain regions requires concurrent noradrenergic activation of the BLA. Electrical physiological studies of unit activity in the auditory cortex will provide novel information on BLA modulation of cortical plasticity, specifically of frequency tuning, sensitivity, and selectivity of auditory information induced by classical conditioning, thus determining the functional consequences of BLA influences on cortical functioning. PUBLIC HEALTH RELEVANCE These findings will significantly increase our understanding of the neurobiological processes that modulate the formation of lasting memories of emotionally significant experiences. The findings will thus be highly relevant for efforts to understand and develop effective treatments for attenuating or preventing emotionally induced disorders, such as posttraumatic stress disorder, that have strong emotional memories as a core component.