Corticoamygdalar regulation of stimulus-outcome memory

皮质杏仁核对刺激结果记忆的调节

• 批准号: 10315218
• 负责人: Alexander Lamparelli
• 金额: $ 4.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-11 至 2024-09-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10315218
• 关键词: Corticoamygdalar; regulation; stimulus; outcome; memory

Project Summary/Abstract Substance use disorder is a chronic, relapsing brain disease characterized by poor decision making, often in the presence of drug-associated cues. Indeed, such cues can elicit cravings and drug seeking, despite known negative consequences of drug use (e.g., illness, overdose). Addictive substances are thought to hijack the brain systems that normally support adaptive motivated behavior, resulting in maladaptive drug-seeking behavior. Thus they may produce maladaptive drug seeking by causing dysfunction in the brain’s ability to retrieve the stimulus-outcome associative memories that are crucial for mentally simulating (i.e., representing) possible future rewarding and aversive outcomes. But very little is known of the neural circuitry that enables these stimulus-outcome memories and even less about the systems that allow these memories to adapt following a shift in the predicted outcome’s value. In order to gain insight into how pathological states arise and determine what can be done to combat them, the goal of this research is to elucidate the brain mechanisms that support the retrieval of stimulus-outcome value memories and the use of such memories to promote adaptive behavior following a negative experience with the predicted reward. Recent studies in rodents and humans have indicated that the basolateral amygdala is a brain region crucial for stimulus-outcome associative memories, but the neural circuitry through which it achieves this function is unknown. I will conduct a critical, in-depth, and hypothesis-driven investigation of the contribution of the basolateral amygdala and its reciprocal connections with the medial orbitofrontal cortex, a region critical for considering potential future outcomes during decision making, in the retrieval of stimulus-outcome memories and use of these memories to guide adaptive behavior when a once-pleasurable event has become aversive. I will receive training in projection-specific chemogenetic manipulation, projection-specific activity monitoring, and behavioral procedures with translational relevance to symptoms of human mental illness to uncover the function of basolateral amygdala-medial orbitofrontal cortex loops in adaptive motivated behavior. I have selected sponsors to provide training on each technical and intellectual aspect of the project, and on career advancement more broadly. Further, completing this project at UCLA ensures I will have access to a highly collaborative network of leading neuroscientists to receive project feedback and any additional training as needed. This award will provide training to help launch me into an independent career as an addiction neuroscientist studying how addictive substances hijack the brain systems that evolved to support adaptive motivated behavior.

项目概要/摘要 药物滥用障碍是一种慢性、复发性脑部疾病，其特征是决策失误，通常发生在 存在与药物相关的线索。事实上，尽管已知，此类线索可能会引起渴望和寻求药物 吸毒的负面后果（例如疾病、服药过量）。成瘾物质被认为会劫持大脑 通常支持适应性动机行为的系统，导致适应不良的药物寻求行为。 因此，它们可能会导致大脑检索药物的能力出现功能障碍，从而产生适应不良的药物寻求。 刺激-结果联想记忆对于心理模拟（即代表）可能至关重要 未来的奖励和厌恶结果。但我们对实现这些功能的神经回路知之甚少。 刺激结果记忆，更不用说让这些记忆适应以下的系统了 预测结果值的变化。为了深入了解病理状态如何产生并确定 可以采取什么措施来对抗它们，这项研究的目标是阐明支持这些现象的大脑机制 刺激结果价值记忆的检索以及使用此类记忆来促进适应性行为 在经历了预期奖励的负面经历之后。 最近对啮齿动物和人类的研究表明，基底外侧杏仁核是大脑中至关重要的区域 对于刺激-结果联想记忆，但它实现这一功能的神经回路是 未知。我将对科学的贡献进行批判性的、深入的、以假设为驱动的调查。 基底外侧杏仁核及其与内侧眶额皮质的相互联系，该区域对于 在决策过程中、在刺激结果记忆的检索过程中考虑潜在的未来结果 当曾经令人愉快的事件变得令人厌恶时，利用这些记忆来指导适应性行为。我 将接受特定于预测的化学遗传学操作、特定于预测的活动监测的培训，以及 与人类精神疾病症状具有转化相关性的行为程序以揭示其功能 适应性动机行为中基底外侧杏仁核-内侧眶额皮层环路的影响。我已选择 赞助商提供项目各个技术和智力方面以及职业发展的培训 更广泛地说。此外，在加州大学洛杉矶分校完成这个项目确保我能够获得高度协作的机会 领先的神经科学家网络，用于接收项目反馈和所需的任何额外培训。本次获奖 将提供培训，帮助我成为一名独立的职业成瘾神经科学家，研究如何 成瘾物质劫持了进化来支持适应性动机行为的大脑系统。