Corticoamygdalar regulation of stimulus-outcome memory

皮质杏仁核对刺激结果记忆的调节

• 批准号: 10676299
• 负责人: Alexander Lamparelli
• 金额: $ 4.22万
• 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/10676299
• 关键词: Adaptive Behaviors; Address; Amygdaloid structure; Anatomy; Appetitive Behavior; Association Learning; Award; Behavior; Behavioral; Behavioral Paradigm; Brain; Brain Diseases; Brain region; Calcium; Career Mobility; Characteristics; Chronic; Compulsive Behavior; Cues; Data Analyses; Decision Making; Desire for food; Development; Dissection; Drug usage; Ensure; Event; Exposure to; Feedback; Fiber; Food; Functional disorder; Future; Genetic; Goals; Human; Image; Immunohistochemistry; Individual; Investigation; Knowledge; Learning; Medial; Memory; Mental disorders; Methods; Monitor; Motivation; Neurobehavioral Manifestations; Neurosciences; Outcome; Overdose; Pathologic; Pathway interactions; Pattern; Pharmaceutical Preparations; Photometry; Play; Positioning Attribute; Procedures; Property; Psyche structure; Regulation; Relapse; Research; Retrieval; Rewards; Rodent; Role; Signal Transduction; Stimulus; Substance Use Disorder; Symptoms; System; Taste aversion; Testing; Training; Update; addiction; calcium indicator; career; combat; conditioning; craving; defined contribution; drug seeking behavior; emotional experience; experience; flexibility; genetic manipulation; insight; maladaptive behavior; memory retrieval; motivated behavior; neural circuit; outcome prediction; response; reward anticipation; sensory integration; simulation; skills; theories; tool

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.

项目摘要/摘要 药物使用障碍是一种慢性，复发的脑部疾病，其特征是决策不良，通常在 存在与药物相关线索的存在。确实，这样的提示可以引起渴望和寻求毒品，目的地已知 药物使用的负面后果（例如疾病，用药过量）。人们认为上瘾的物质劫持了大脑 通常支持自适应分子的系统，导致不良适应药物寻求药物的行为。 他们可能会通过在大脑检索能力中引起功能障碍而产生适应不良的药物。 刺激结果的关联记忆，对于可能的模拟（即表示）至关重要 未来的有益和厌恶结果。但是，对于使这些的神经回路知之甚少 刺激性结果记忆，甚至更少关于允许这些记忆适应后的系统 预测结果价值的转变。为了深入了解病理状态的出现并确定 可以采取什么措施来对抗它们，这项研究的目的是阐明支持的大脑机制 检索刺激结果的价值记忆和使用这种记忆来促进适应性行为 遵循预测奖励的负面经历。 最近对啮齿动物和人类的研究表明，基底外侧杏仁核是一个至关重要的大脑区域 对于刺激结果的关联记忆，但是通过它实现此功能的神经电路是 未知。我将对有关该贡献的批判性，深入和假设驱动的研究 基底外侧杏仁核及其与介质轨道额皮层的相互连接，这是一个至关重要的区域 在决策过程中考虑潜在的未来结果，以获取刺激结果记忆 并使用这些记忆来指导自适应行为时，一度令人愉悦的事件变得厌恶。 将接受投影特异性化学发生操作，投影特异性活动监测和 行为程序与人类精神疾病症状的转化相关性，以发现功能 基底外侧杏仁核 - 甲状腺甲状腺皮质循环在适应性动机的行为中。我选择了 发起人提供有关项目的每个技术和智力方面以及职业发展的培训 更广泛。此外，在加州大学洛杉矶分校完成此项目可确保我可以访问高度协作 领先的神经科学家网络将根据需要获得项目反馈和任何其他培训。这个奖项 将提供培训，以帮助我成为成瘾神经科学家的独立职业，研究如何 其他物质劫持了发展以支持适应性动机行为的大脑系统。