Amygdala-cortical circuitry in reward encoding, expectation, and decision making

项目摘要 越来越多的证据表明，许多精神疾病的认知症状，包括 成瘾是由于未能适当地了解和/或预测潜在的未来事件。的确， 在被诊断为患有抑郁症的患者中， 成瘾，解释他们无法限制使用，尽管有害的后果。类似的赤字 在被诊断患有与成瘾共病的精神疾病的患者中，如抑郁症，焦虑症， 和精神分裂症这些精神疾病是美国主要的棘手的公共卫生问题， 数千亿美元的成本与医疗保健，犯罪，监禁和执法。 因此，迫切需要预防和/或治疗这些病症的有效方法。这个目标 研究的目的是揭示学习预测关系所需的神经回路，并利用这些信息， 产生对未来的期望，以便深入了解病理状态如何产生和决定 我们可以做些什么来对抗它们。 成瘾物质被认为会劫持通常支持适应性决策的大脑系统， 导致不适应的选择。适应性决策需要准确的前瞻性考虑， 未来可能的事件。特定刺激-奖励关联记忆的先前编码使得这种前瞻性的 通过允许心理模拟（即，未来可能的奖励活动。最近 对啮齿动物和人类的研究表明，基底外侧杏仁核（BLA）可能是一个大脑区域， 这对学习这些联系至关重要，但确切地说，它是如何实现的，以及它通过什么神经回路来实现这一点， 功能未知。拟议的研究提供了一个关键的，深入的，假设驱动的调查 BLA的贡献及其与眶额皮质的相互联系，眶额皮质是一个涉及 决策，刺激奖励编码和随后的检索这一信息，以指导适应性 行为和选择。这将通过多方面和综合的神经记录来实现， 操纵方法。我们将结合联合收割机项目特定的活动监测，标签和捕获技术， 操纵特定的事件激活的神经元集合，和行为程序与翻译 与人类精神疾病症状的相关性，以揭示杏仁核-皮层回路在适应性 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.