Corticoamygdalar regulation of stimulus-outcome memory

项目总结/摘要 物质使用障碍是一种慢性、复发性脑部疾病，其特征是决策能力差，通常发生在 药物相关线索的存在。事实上，这些线索可以引起渴望和药物寻求，尽管已知的 吸毒的负面后果（例如，疾病，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，他们可能会产生适应不良的药物寻求造成功能障碍，在大脑的能力，以检索 刺激-结果关联记忆对于心理模拟至关重要（即，代表）可能的 未来的奖励和厌恶的结果。但我们对这些神经回路知之甚少， 刺激-结果记忆，甚至更少关于允许这些记忆在一个 预测结果值的变化。为了深入了解病理状态是如何产生和决定 我们可以做些什么来对抗它们，这项研究的目标是阐明支持这些疾病的大脑机制。 刺激-结果价值记忆的恢复以及使用这些记忆来促进适应行为 在预期奖励的负面体验之后。 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-结果关联记忆，但通过它实现这一功能的神经电路是 未知我将进行一个关键的，深入的，假设驱动的调查的贡献， 基底外侧杏仁核及其与内侧眶额皮质的相互联系，这是一个关键区域， 在决策过程中考虑潜在的未来结果，在刺激-结果记忆的检索中 当一个曾经令人愉快的事件变得令人厌恶时，这些记忆可以用来指导适应性行为。我 将接受特定项目化学遗传学操作、特定项目活动监测和 行为程序与人类精神疾病症状的翻译相关性，以揭示功能 基底外侧杏仁核-内侧眶额皮层环路的变化。我选择 赞助商提供项目的每个技术和知识方面的培训，以及职业发展 更广泛地说。此外，在加州大学洛杉矶分校完成这个项目，确保我将有机会获得一个高度合作的 领先的神经科学家网络，以接收项目反馈和任何额外的培训。这个奖项 我将提供培训，帮助我进入一个独立的职业生涯，作为一个成瘾神经学家，研究如何 成瘾物质劫持了大脑系统，而大脑系统的进化是为了支持适应性动机行为。

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.