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

多巴胺神经元是否通过对基底外侧杏仁核和中央杏仁核的不同投射来介导目标导向学习和习惯学习？

• 批准号: 10753405
• 负责人: Kate M Wassum
• 金额: $ 23.55万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753405
• 关键词: Address; Amygdaloid structure; Anxiety; Basic Science; Behavior; Behavior Control; Behavior assessment; Brain; Cell Nucleus; Cognitive; Coupled; Data; Decision Making; Desire for food; Disease; Dissection; Dopamine; Emotional; Equilibrium; Evaluation; Event; Exposure to; Foundations; Fright; Functional disorder; Future; Goals; Habits; Investigation; Knowledge; Lateral; Learning; Lesion; Mediating; Memory; Mental Depression; Mental disorders; Midbrain structure; Modeling; Modernization; Monitor; Motivation; Neurobehavioral Manifestations; Neuromodulator; Neurons; Neurosciences; Obesity; Obsessive-Compulsive Disorder; Operant Conditioning; Optics; Outcome; Pathologic; Pathway interactions; Policies; Psychological reinforcement; Rewards; Role; Schizophrenia; Signal Transduction; Substance Use Disorder; System; Testing; Ventral Tegmental Area; Work; autism spectrum disorder; cell type; comparative; dopaminergic neuron; flexibility; habit learning; innovation; learning outcome; neuronal circuitry; neurotransmission; novel; optogenetics; prospective; response; sensor; success; theories; tool

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.

项目概要 在做出决定时，我们可以利用对现有行动与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当前最有利的目标-。 因此，定向策略非常灵活，使我们能够在情况发生变化时随时调整我们的行为。 我们并不总是考虑我们行为的后果，这样的习惯对我们来说是一种很好的方式。 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、在适当的时候进行适应，但会破坏目标导向的学习和过度依赖。 对习惯的依赖可能会导致对后果考虑不足、缺乏灵活性、强迫性阈值较低，以及 这可能会导致许多疾病，包括药物滥用障碍。 （SUD）、强迫症、肥胖、精神分裂症、抑郁症、焦虑症和自闭症的障碍。 机械理解是缺乏支持行动结果的神经回路信息 因此，我们的总体目标是揭示调节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。 表明支持习惯学习的奖励预测错误，但新的证据表明中脑。 多巴胺在学习中的作用比最初想象的要广泛得多，包括对目标导向的贡献 多巴胺如何支持这两种通常相反的学习形式？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预测来实现的，我们将揭示其途径。 使多巴胺在习惯形成和行动结果学习中发挥作用。 多巴胺可能通过对杏仁核的投射来调节行动结果和习惯学习。 杏仁核 (BLA) 对于行动结果学习至关重要，相比之下，杏仁核 (CeA) 的中央核。 人们早就知道中脑多巴胺投射到 BLA 和 CeA 的存在，但是 我们对它们的功能知之甚少，我们将在这里揭示我们的工具学习中每个途径的功能。 假设中脑多巴胺投射到 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方法在两个目标上测试这一假设。 系统神经科学工具，包括基于荧光传感器的多巴胺监测以及细胞类型和通路- 特定的、双向的、光遗传学操作加上理论驱动的行为评估 通过针对具体结果的贬值和遗漏应急测试进行结果和习惯学习。 为我们从机械角度理解破坏原因的长期目标奠定了关键的基础科学基础 病理状态下的决策和适应不良习惯。