Psychobiology of conditioned memory modulation

在经典的条件反射中，条件刺激(“CS”--一种环境、声音、气味)是一种相对中性的刺激，在与具有生物学意义的刺激(非条件刺激；“美国”--食物、休克、各种药物)联系在一起后，就会触发习得的或“条件的”反应。条件性反应通常是相当复杂的，因为它们包括运动、情绪和生理反应。这项拨款申请的研究将探索“条件性记忆调制”，重点是CS如何调节新获得的记忆的强度。我的实验室是第一个对CS与激励性和厌恶性USS组合的记忆调制进行系统的经验比较的实验室。由于CS的调节作用似乎与它们相关的USS没有区别，并且在它们不存在的情况下被观察到，我们认为习得的CS可以获得独立调节大脑记忆系统活动的能力。在这项申请中提出的研究的首要目标是确定CS调节记忆巩固的关键心理和神经生物学机制；这是一个稳定新形成的记忆痕迹的依赖于时间的神经生物学过程。拟议的科学方法将涉及雄性和雌性Spraogue-Dawley实验室大鼠的条件反射程序，通过训练后暴露于CS/USS来调节记忆巩固，记忆测试(物体身份/位置识别)，药理学，以及通过直接注入离散大脑区域的化合物来操纵神经活动。在接下来的五年中，目标是探索胆碱能、去甲肾上腺素和多巴胺能机制/通路，以及扩展的杏仁核及其投射，在CS及其USS调节记忆巩固中的作用。我们还设计了一些研究，以阐明不同的CS心理功能如何影响记忆巩固。这项研究将为至少6名博士、5名硕士和17名本科生提供培训机会。提出的研究方案代表了一种新的心理学和神经生物学相结合的研究，即条件刺激对记忆的调节。条件反射过程在人类和动物行为中扮演着许多角色，而条件反射可能会影响新形成的记忆的稳定性，这表明人们普遍参与了正常的学习功能。此外，条件性因素在物质依赖和创伤后应激障碍等精神病理学中发挥着重要作用。因此，对CS如何影响记忆的详细了解最终可以刺激替代的心理和药理学方法，以改善许多受这些衰弱疾病影响的加拿大人的生活。

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.