Investigating the regulation of mesolimbic dopamine during reward-guided action selection and inhibition

研究奖励引导的动作选择和抑制过程中中边缘多巴胺的调节

• 批准号: 2104945
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2104945
• 关键词: Investigating; regulation; mesolimbic; dopamine; during

A substantial body of work has implicated mesolimbic dopamine as an integral component of reward-guided decision-making. Midbrain dopamine activity and release in the nucleus accumbens (NAcc) scales with predictions of future reward, and manipulations of dopamine in the NAcc can change how animals respond to and approach reward-predicting cues. However, in certain contexts, it can actually be advantageous to refrain from responding in the presence of a reward opportunity in order to achieve the greater future benefits. Crucially, we (1) have recently shown that in exactly such situations of action restraint, dopamine reward value signals in the NAcc are suppressed compared to when they need to make a response to gain reward. This finding dovetails with a number of other studies that have shown that mesolimbic dopamine, and reward-guided behaviour, can be contextually regulated by afferent brain regions, in concert with local neuromodulatory control (e.g., 2). It also aligns with increasing interest, including from Lundbeck teams, in the idea that an imbalance in mesolimbic dopamine and dysfunctional reward processing may be a transdiagnostic hallmark of many neuropsychiatric disorders (3,4). The key unresolved questions now are where and under what circumstances this regulation of dopamine occurs, and how this regulation supports appropriate reward-guided behaviour. The project will address these critical issues by measuring and manipulating mesolimbic dopamine in rodents performing sophisticated reward-based behavioural tasks. The collaborative studentship brings together researchers in Experimental Psychology at the University of Oxford at the forefront of research into how neurochemistry influences reward-guided behaviours with scientists at Lundbeck who have expertise in translational research and extensive knowledge in dopamine pharmacology and alterations in neuropsychiatric disease states.

大量工作表明，中脑边缘多巴胺是奖励导向决策的一个组成部分。中脑多巴胺在伏隔核(NAcc)的活动和释放与对未来奖励的预测有关，而对NAcc中的多巴胺的操纵可以改变动物对奖励预测线索的反应和接近。然而，在某些情况下，为了获得更大的未来利益，避免在有奖励机会的情况下做出回应实际上可能是有利的。最重要的是，我们(1)最近证明，在这种行为约束的情况下，与需要做出反应以获得奖励时相比，NAcc中的多巴胺奖赏价值信号受到抑制。这一发现与其他一些研究相吻合，这些研究表明，中脑边缘多巴胺和奖赏引导行为可以受到大脑传入区域的上下文调节，与局部神经调节控制(例如，2)相一致。这也与包括Lundbeck团队在内的越来越多的人的兴趣一致，他们认为中脑边缘多巴胺的不平衡和功能失调的奖励处理可能是许多神经精神障碍的跨诊断特征(3，4)。目前关键的悬而未决的问题是，多巴胺的这种调控是在什么情况下以及在哪里发生的，以及这种调控如何支持适当的奖赏引导行为。该项目将通过测量和操纵执行复杂的基于奖励的行为任务的啮齿动物的中脑边缘多巴胺来解决这些关键问题。这个合作项目汇集了牛津大学实验心理学的研究人员和伦贝克大学的科学家，他们在神经化学如何影响奖励引导行为的研究中处于领先地位，他们在翻译研究方面拥有专业知识，在多巴胺药理学和神经精神疾病状态的改变方面拥有丰富的知识。