Psychobiology of conditioned memory modulation

在经典条件反射中，条件刺激（“CS”-环境，声音，气味）是一种相对中性的刺激，在与生物学上重要的刺激（无条件刺激;“US”-食物，休克，各种药物）相关联后，会触发习得或“条件”反应。条件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。这项研究将探索“条件记忆调制”，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进行系统的经验比较的记忆调制与激励和厌恶的美国配对CS。由于CSs的调节作用似乎与其相关的USs的调节作用难以区分，并且在它们不存在的情况下观察到，因此我们认为，学习的CSs可以获得独立调节大脑中记忆系统活动的能力。本申请中提出的研究的总体目标是确定关键的心理和神经生物学机制，CSs调节记忆巩固;新形成的记忆痕迹稳定的时间依赖性神经生物学过程。 拟定的科学方法将涉及雄性和雌性Sprague-Dawley实验室大鼠的条件反射程序、通过训练后暴露于CS/US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脑区的化合物操纵神经活动。在接下来的五年里，我们的目标是探索胆碱能，去甲肾上腺素能和多巴胺能的机制/途径，以及扩展杏仁核及其预测，在调制的记忆巩固的CS和他们的US的作用。我们还设计了研究，以阐明不同的心理功能的CSs影响记忆巩固。这项研究将为至少6名博士，5名硕士和17名本科论文学生提供培训机会。该研究计划代表了一种新的综合心理学和神经生物学研究的记忆调制的条件刺激。条件反射过程在人类和动物的行为中扮演着许多角色，而条件反射影响新形成的记忆的稳定性的可能性表明，条件反射普遍参与正常的学习功能。此外，条件反射因素在物质依赖和创伤后应激障碍等精神病理学中发挥重要作用。因此，详细了解CS如何影响记忆，最终可以刺激替代心理和药理学方法，以改善许多受这些衰弱状况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.