Psychobiology of conditioned memory modulation

点击翻译按钮获取中文摘要

In classical conditioning, the conditioned stimulus ("CS" - an environment, sound, smell) is a relatively neutral stimulus that, after association with a biologically significant stimulus (the unconditioned stimulus; "US" - food, shock, various drugs), comes to trigger learned or "conditioned" responses. Conditioned responses are typically quite complex as they encompass motor, emotional, and physiological reactions. The research in this grant application will explore "conditioned memory modulation," focussing on how CSs modulate the strength of newly acquired memories. My laboratory has been the first to conduct a systematic empirical comparison of memory modulation by CSs paired with incentive and aversive USs. Because the modulatory effects of CSs appeared indistinguishable from those of their associated USs, and were observed in their absence, we suggested that learned CSs can gain the ability to independently modulate activity of memory systems in the brain. The overarching objective of the research proposed in this application is to identify key psychological and neurobiological mechanisms by which CSs modulate memory consolidation; a time-dependent neurobiological process of stabilization of newly formed memory traces. The proposed scientific approach will involve conditioning procedures in both male and female Sprague-Dawley laboratory rats, modulation of memory consolidation by post-training exposure to CSs/USs, memory testing (object identity/location recognition), pharmacology, as well as manipulations of neural activity by compounds infused directly in discrete brain regions. In the next five years, the aims are to explore the roles of cholinergic, noradrenergic, and dopaminergic mechanisms/pathways, as well as of the extended amygdala and its projections, in modulation of memory consolidation by CSs and their USs. We have also designed studies to elucidate how different psychological functions of CSs impact memory consolidation. This research will provide training opportunities for at least 6 PhD, 5 MSc, and 17 Undergraduate Thesis students. The proposed research program represents a novel integrative psychological and neurobiological investigation of memory modulation by conditioned stimuli. Conditioning processes play many roles in human and animal behavior, and the possibility that CSs impact the stability of newly formed memories suggests a ubiquitous involvement in normal learning functions. Moreover, conditioning factors play important roles in psychopathologies such as substance dependence and post-traumatic stress disorders. Therefore, a detailed understanding of how CSs impact memory can eventually spur alternative psychological and pharmacological approaches to improve the lives of many Canadians affected by these debilitating conditions.