A gut-brain interaction controlling reward learning

项目摘要/摘要 纹状体中脑多巴胺系统活性变化所支持的功能和计算是 这是现代神经科学中研究最多、争论最激烈的一些话题。主导性理论 建议它们通过广播预测误差信号来支持强化学习，编码刺激 显着性，或通常通过代表内部状态来激励奖励寻求。此外，它还被广泛接受 这些系统是由自然选择塑造的，以加强适应行为。吃，还是追求 营养，是生存的基础，以前的工作已经证明纹状体DA回路是关键 支持这种行为的神经生物系统的组成部分。重要的是，新兴研究支持 一个模型，通过该模型，中脑DA人群从肠道接收关于食物内容的信号，这些信号改变了他们的 活动，并有助于食物学习和动力。然而，这些肠子衍生的时间尺度 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，我们建议解决我们知识中的这些差距 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 它们被摄食后的信号招募来控制食物奖励。2)表征进食后的能力 通过影响纹状体亚区的多巴胺释放来改变奖赏学习的信号。3)检验因果关系 摄食后信号在多巴胺控制食物奖赏中的作用。为了实现这些目标，我们有 组建了一个团队，其中包括行为和系统神经学家，他们拥有现代技术方面的专业知识 记录和操纵基因定义的细胞群体，具有以下专业知识的翻译神经学家 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。这些研究的完成将提供一个整合的机会 中脑多巴胺系统对多巴胺控制奖赏学习的当前模型的外周调制 和动机，并为今后研究外周-中枢多巴胺对 多种适应功能和疾病状态。

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.