Do dopamine neurons mediate both goal-directed and habit learning via distinct projections to basolateral versus central amygdala?

项目总结 在做出决策时，我们可以利用我们对可用行动-结果关系的理解来前瞻性地 评估我们潜在行动的后果，并选择目前最有益的行动。这个目标-- 因此，定向策略非常灵活，允许我们在环境变化时随时调整自己的行为。但 我们并不总是考虑我们行为的后果。通常这是很好的。这些习惯是我们的一种方式 大脑有效地执行日常行为。目标导向和习惯性控制之间的平衡允许行为 在需要时保持适应性，但在适当时保持效率。但扰乱了目标导向的学习和过度依赖 习惯会导致对后果的不充分考虑，缺乏灵活性，强制性的门槛较低，以及 打乱了决策。这可能导致多种疾病，包括物质使用障碍。 强迫症、肥胖症、精神分裂症、抑郁症、焦虑症和自闭症。对…的障碍 机械论理解是缺乏关于支持动作-结果和神经回路的信息 习惯学习。因此，我们的广泛目标是揭示控制这两种学习形式的神经通路。 中脑多巴胺神经元长期以来一直被认为与学习有关。经典地说，他们被认为 发出支持习惯学习的奖励预测错误的信号。但新出现的证据表明，中脑 多巴胺在学习中的作用比最初认为的要广泛得多，包括对目标导向的贡献。 学习。多巴胺如何支持这两种通常相互对立的学习形式？我们的解决方案很简单： 多巴胺在学习中的不同功能是通过其不同的投射来实现的。我们将揭示这些路径 这使得多巴胺在习惯形成和行动结果学习中都起到了作用。 多巴胺可能通过投射到杏仁核来调节行为结果和习惯学习。基底外侧 杏仁核(BLA)对动作-结果学习至关重要。相比之下，杏仁中央核(CEA) 调节习惯学习。中脑多巴胺对BLA和CEA的投射早已为人所知，但 人们对它们的功能知之甚少。我们将在这里揭示每条途径在工具性学习中的作用。我们的工作 假说是中脑多巴胺投射到BLA支持行动-结果学习和多巴胺 对CEA的预测支持习惯学习。我们将使用一套现代的 系统神经科学工具，包括基于荧光传感器的多巴胺监测和细胞类型和途径- 特定的、双向的、光遗传操作与理论驱动的行动行为评估相结合- 通过特定结果贬值和遗漏权变测试的结果和习惯学习。这将提供一个 重要的基础科学基础，为我们从机制上理解混乱原因的长期目标奠定基础 疾病状态下的决策和不适应习惯。

PROJECT SUMMARY When making a decision we can use our understanding of available action-outcome relationships to prospectively evaluate the consequences of our potential actions and choose the one that is currently most beneficial. This goal- directed strategy is, thus, quite flexible, allowing us to readily adapt our behavior when circumstances change. But we don’t always think about the consequences of our behavior. Usually this is fine. Such habits are a way for our brain to efficiently execute routine behaviors. A balance between goal-directed and habitual control allows behavior to be adaptive when needed, but efficient when appropriate. But disrupted goal-directed learning and overreliance on habit can cause inadequate consideration of consequences, inflexibility, a lower threshold for compulsivity, and disrupted decision making. This can contribute to aspects of numerous diseases, including substance use disorder (SUD), obsessive-compulsive disorder, obesity, schizophrenia, depression, anxiety, and autism. An obstacle to mechanistic understanding is the dearth of information on the neuronal circuits that support action-outcome and habit learning. Thus, our broad goal is to expose neuronal pathways regulating both forms of learning. Midbrain dopamine neurons have long been implicated in learning. Canonically, they have been thought to signal the reward prediction errors that support habit learning. But emerging evidence indicates that midbrain dopamine has a much broader role in learning than originally thought, including contributions to goal-directed learning. How can dopamine support both these, often opposing, forms of learning? Our solution is simple: dopamine’s different functions in learning are achieved through its different projections. We will reveal the pathways that enable dopamine function in both habit formation and action-outcome learning. Dopamine may mediate action-outcome and habit learning via projections to the amygdala. The basolateral amygdala (BLA) is critical for action-outcome learning. By contrast, the central nucleus of the amygdala (CeA) mediates habit learning. Midbrain dopamine projections to the BLA and CeA have long been known to exist, but little is known of their function. We will reveal a function for each pathway in instrumental learning here. Our working hypothesis is that midbrain dopamine projections to the BLA support action-outcome learning and dopamine projections to the CeA support habit learning. We will test this hypothesis in two aims using a suite of modern systems neuroscience tools including fluorescent sensor-based dopamine monitoring and cell-type and pathway- specific, bidirectional, optogenetic manipulation coupled with theory-driven behavioral assessment of action- outcome and habit learning with outcome-specific devaluation and omission contingency tests. This will provide a critical basic science foundation for our long-term goal of mechanistic understanding of the causes of disrupted decision making and maladaptive habits in pathological states.