Amygdala-cortical Circuitry in Reward Encoding, Expectation, and Decision Making

项目总结 越来越多的证据表明，许多精神障碍背后的认知症状，包括 上瘾，是由于未能适当地了解和/或预测潜在的未来事件造成的。的确， 在确诊的患者中发现在对潜在奖励事件的前瞻性考虑方面存在缺陷 与成瘾有关，这是他们不顾有害后果而无法限制使用的原因。类似的赤字也有 在被诊断为患有精神疾病和成瘾的患者中被发现，如抑郁，焦虑， 和精神分裂症。这些精神疾病在美国是主要的棘手的公共卫生问题， 与医疗保健、犯罪、监禁和执法相关的数千亿美元成本。 因此，迫切需要有效的方法来预防和/或治疗这些疾病。这样做的目的是 研究是揭示学习预测关系所需的神经回路，并使用这些信息来 产生对未来的预期，以便深入了解病理状态是如何产生和决定的 我们可以做些什么来对抗他们。 令人上瘾的物质被认为劫持了通常支持适应性决策的大脑系统， 导致了不适应的选择。适应性决策需要准确的前瞻性考虑 未来可能发生的事件。对特定刺激-奖赏联想记忆的预先编码使这种预期成为可能 通过允许对未来可能的奖励事件进行心理模拟(即，表征)来进行考虑。近期 对啮齿动物和人类的研究表明，基底外侧杏仁核(BLA)可能是大脑的一个区域 对于学习这些联系至关重要，但确切地说，它是如何实现这一点的，以及它通过神经回路实现这一点 功能都是未知的。建议的研究提供了关键的、深入的和假设驱动的调查 BLA的贡献及其与眶前皮质的相互联系，该区域涉及 决策，以刺激-奖赏编码和随后的信息提取来引导适应性 行为和选择。这将通过多方面和综合的神经记录和 操纵方法。我们将结合特定于投影的活动监视、标记和捕获技术 特定事件激活的神经元集合的操纵，以及翻译的行为程序 与人类精神疾病症状的相关性以揭示大脑皮质环在适应性中的功能 奖励导向的行为和决策。

PROJECT SUMMARY Growing evidence suggests that the cognitive symptoms underlying many psychiatric disorders, including addiction, result from a failure to appropriately learn about and/or anticipate potential future events. Indeed, deficits in the prospective consideration of potential rewarding events have been detected in patients diagnosed with addiction, accounting for their inability to limit use despite deleterious consequences. Similar deficits have been identified in patients diagnosed with mental illnesses comorbid with addiction, such as depression, anxiety, and schizophrenia. These mental illnesses are major intractable public health problems in the US, accounting for hundreds of billions of dollars in costs associated with health care, crime, incarceration and law enforcement. Effective approaches to prevent and/or treat these conditions are, therefore, badly needed. The goal of this research is to expose the neural circuits required to learn predictive relationships and to use this information to generate expectations about the future, in order to gain insight into how pathological states arise and determine what can be done to combat them. Addictive substances are thought to hijack the brain systems that normally support adaptive decision making, resulting in maladaptive choices. Adaptive decision making requires accurate prospective consideration of possible future events. Prior encoding of specific stimulus-reward associative memories enables this prospective consideration by allowing the mental simulation (i.e., representation) of possible future rewarding events. Recent studies in rodents and humans have indicated that the basolateral amygdala (BLA) might be a brain region crucial for learning these associations, but precisely how and the neural circuitry through which it achives this function are unknown. The proposed research provides a critical, in-depth, and hypothesis-driven investigation of the contribution of the BLA and its reciprocal connections with the orbitofrontal cortex, a region implicated in decision making, to stimulus-reward encoding and subsequent retrieval of this information to guide adaptive behavior and choice. This will be achieved through a multi-faceted and integrative neural recording and manipulation approach. We will combine projection-specific activity monitoring, tag and capture techniques for manipulation of specific event-activated neuronal ensembles, and behavioral procedures with translational relevance to symptoms of human mental illness to uncover the function of amgydala-cortical loops in adaptive reward-guided behavior and decision making.