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.

项目摘要 做出决定时，我们可以利用对可用行动结果关系的理解 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，使我们能够在情况发生变化时很容易地适应我们的行为。 我们并不总是考虑行为的后果。通常这很好。这样的习惯是我们的一种方式 大脑有效执行常规行为。目标指导和习惯控制之间的平衡允许行为 需要在需要时进行自适应，但在适当的时候有效。但是被破坏的目标指导学习和过度依赖 习惯会导致对后果，僵化性，强迫性较低的阈值以及 破坏决策。这可能有助于多种疾病的方面，包括药物使用障碍 （SUD），强迫症，肥胖，精神分裂症，抑郁，焦虑和自闭症。一个障碍 机械理解是有关支持动作结果和的神经元电路信息的死亡 习惯学习。这是我们的广泛目标是揭露调节两种学习形式的神经元途径。 长期以来，中脑多巴胺神经元在学习中一直暗示。从规范上讲，他们被认为 向支持习惯学习的奖励预测错误发出信号。但是新兴的证据表明中脑 多巴胺在学习中的作用比最初想象的要广泛，包括对目标定向的贡献 学习。多巴胺如何支持这两种经常相反的学习形式？我们的解决方案很简单： 多巴胺在学习方面的不同功能是通过其不同的项目实现的。我们将揭示路径 这使多巴胺在习惯形成和行动结果学习中都可以发挥作用。 多巴胺可以通过项目向杏仁核调解行动结果和习惯学习。基础 杏仁核（BLA）对于行动结果学习至关重要。相比之下，杏仁核的中央核（CEA） 调解习惯学习。长期以来，已知存在于BLA和CEA的中脑多巴胺项目，但 对它们的功能知之甚少。我们将在这里揭示每种途径的功能。我们的工作 假设是中脑多巴胺向BLA支持动作结果学习和多巴胺 CEA的预测支持习惯学习。我们将使用一套现代的套件在两个目标中检验这一假设 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途径 - 特定的，双向的，光学遗传的操纵以及理论驱动的行为评估 结局和习惯学习，具有特定结果的定义和省略应急测试。这将提供一个 批判基础科学基金会是我们对破坏原因的机械理解的长期目标 病理状态的决策和适应不良习惯。