A gut-brain interaction controlling reward learning

控制奖励学习的肠脑相互作用

• 批准号: 10899004
• 负责人: William Matthew Howe
• 金额: $ 24.36万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10899004
• 关键词: Adaptive Behaviors; Address; Anatomy; Appetitive Behavior; Behavior; Behavioral; Big Data; Brain; Calories; Carbohydrates; Cells; Code; Collaborations; Consumption; Corpus striatum structure; Data; Data Analyses; Disease; Dissociation; Dopamine; Dorsal; Drug abuse; Eating; Event; Fatty acid glycerol esters; Fiber; Food; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Human; Immunohistochemistry; Individual; Infusion procedures; Knowledge; Label; Lead; Learning; Link; Macronutrients Nutrition; Measures; Mediating; Mental Depression; Midbrain structure; Modeling; Modernization; Monitor; Motivation; Mus; Natural Selections; Neurobiology; Neurons; Neurosciences; Nucleus Accumbens; Nutrient; Obesity; Optics; Oral cavity; Pathway interactions; Peripheral; Phenotype; Photometry; Play; Population; Proteins; Psychological reinforcement; Research; Research Support; Rewards; Role; Self Stimulation; Shapes; Signal Transduction; Statistical Models; Stimulus; Substantia nigra structure; Support System; System; Techniques; Technology; Testing; Time; Training; Ventral Tegmental Area; Viral Vector; Work; computational neuroscience; design; dopamine system; experimental study; genetic manipulation; gut-brain axis; human subject; neural; novel; recruit; reinforced behavior; response; stem; theories; translational potential

Project Summary/Abstract The functions and computations supported by changes in the activity of meso-striatal dopamine systems are some of the most heavily researched, and hotly debated, topics in modern neuroscience. Predominant theories propose that they support reinforcement learning by broadcasting prediction-error signals, encode stimulus salience, or generally motivate reward seeking by representing internal states. Furthermore, it is widely accepted that these systems have been shaped by natural selection to reinforce adaptive behaviors. Eating, or the pursuit of nutrients, is fundamental for survival, and previous work has demonstrated that striatal DA circuits are critical components of the neurobiological systems that support this behavior. Importantly, emerging research supports a model whereby midbrain DA populations receive signals from the gut about food content that modify their activity and contribute to food learning and motivation. However, the timescale over which these gut-derived signals modulate DA release, and how they interact with DA signals previously identified as critical for food reward learning and motivation, is largely unknown. Here, we propose to address these gaps in our knowledge by using state of the art techniques to 1) Identify the ensembles of neurons in midbrain dopamine populations that are recruited by post-ingestive signals to control food reward. 2) Characterize the ability of post-ingestive signals to modify reward learning via effects on dopamine release in subregions of the striatum. 3)Test the causal role of post-ingestive signals for dopamine control of food reward. To accomplish these aims, we have assembled a team including behavioral and systems neuroscientists with expertise in modern technologies for recording and manipulating genetically defined cell populations, translational neuroscientists with expertise in the neurobiology of appetitive behaviors, statisticians specializing in big-data analysis, as well as leaders in the field of computational neuroscience. Completion of these studies will provide an opportunity to integrate peripheral modulation of midbrain dopamine systems into current models of dopamine control of reward learning and motivation, and provide a foundation for future studies of peripheral-central dopamine contributions to multiple adaptive functions and disease states.

项目总结/摘要 中纹状体多巴胺系统活性变化所支持的功能和计算是 现代神经科学中一些研究最多、争论最激烈的话题。主流理论 我建议他们通过广播预测错误信号，编码刺激来支持强化学习。 显著性，或通常通过表示内部状态来激励奖励寻求。此外，它被广泛接受 这些系统是由自然选择塑造的，以加强适应性行为。吃，还是追求 是生存的基础，以前的工作已经证明纹状体DA回路是至关重要的， 支持这种行为的神经生物学系统的组成部分。重要的是，新兴研究支持 一个模型，中脑DA群体从肠道接收有关食物含量的信号， 活动，并有助于食物的学习和动机。然而，这些肠道衍生的 信号调节DA的释放，以及它们如何与先前被认为对食物至关重要的DA信号相互作用。 奖励学习和动机，在很大程度上是未知的。在这里，我们建议填补我们知识中的这些空白 通过使用最先进的技术来1）识别中脑多巴胺群体中的神经元集合 被摄食后信号招募来控制食物奖赏。2)描述摄食后 通过影响纹状体子区域的多巴胺释放来改变奖励学习的信号。3)测试因果关系 摄入后信号对多巴胺控制食物奖励的作用。为了实现这些目标，我们 组建了一个包括行为和系统神经科学家在内的团队，他们拥有现代技术的专业知识， 记录和操纵遗传定义的细胞群，具有以下专业知识的翻译神经科学家： 食欲行为的神经生物学，专门从事大数据分析的统计学家，以及 计算神经科学领域。完成这些研究将提供一个机会， 中脑多巴胺系统的外周调制进入奖赏学习的多巴胺控制的当前模型 和动机，并提供了一个基础，为未来的研究外周中枢多巴胺的贡献， 多种适应功能和疾病状态。