Functional diversity of the human dopamine system

人类多巴胺系统的功能多样性

• 批准号: 1634179
• 负责人: Samuel McClure
• 金额: $ 52.42万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1634179&HistoricalAwards=false
• 关键词: Functional; diversity; human; dopamine; system

Dopamine, a vital neuromodulator in the brain, is involved in many cognitive processes and behaviors, such as how people make decisions and form memories. Recent animal research suggests that dopamine function, namely how dopamine neuron influence brain activity, is more diverse than previously thought. These animal studies show that the diverse function of dopamine does not come just from the existence of different types of dopamine neurons; instead, it comes from variation in the anatomical structure of the dopamine system in the brain. Different dopamine pathways support different cognitive processes and behaviors, such as reward and punishment, which is significant because such pathways are large enough to study with non-invasive techniques such as magnetic resonance imaging (MRI). This project will use MRI in human participants to achieve two goals: (1) to map dopamine pathways in the human brain and (2) to measure activity from brain regions where dopamine neurons are and brain regions that receive dopamine input. This research is important because it employs non-invasive neuroimaging methods in humans to test and expand ideas from animal research. Studying humans has the promise to directly impact and improve understanding of dopamine-mediated behaviors, which are broadly relevant to many areas of psychology and social science. This research project therefore will contribute to an improved understanding of the brain basis of decision-making, enabling insight into how altered brain function, such as occurs with aging and mental health disorders, influences behavior. The dopamine system is involved in many fundamental cognitive and behavioral processes. To date, subclasses of dopamine neurons have been identified that respond to rewards, aversive stimuli, or equally to reward and aversive stimuli. Importantly, recent evidence from both rodent and nonhuman primate studies shows that certain dopaminergic pathways support reward learning and conditioned place preference, while other dopaminergic pathways support learned aversion and conditioned place avoidance. Collectively this body of animal work, which spans multiple labs and species, supports the idea that the dopamine system has anatomically defined heterogeneity. This project proposes to test the hypothesis that dopaminergic function itself is diverse and not consistent with uniform transmission of reward prediction errors. The PIs will use functional magnetic resonance imaging (fMRI) and diffusion-weighted images (DWI) combined with probabilistic tractography methods to study functional and white matter connectivity patterns of mesolimbic dopamine networks, which include the brainstem substantia nigra and ventral tegmental area (SN/VTA), during learning tasks mediated by rewarding and aversive outcomes. This endeavor is noteworthy because it extends neuroimaging of the brainstem to include DWI, which enables white matter connectivity measurements between the mesencephalon, striatum and cortex, and because it has the potential to make a fundamental contribution to how decision neuroscience understands dopamine-mediated behaviors. This research contributes to the central aims of neuroeconomics, an evolving interdisciplinary field that provides an exciting educational opportunity for undergraduate and graduate students interested in neuroscience, decision-making, or the social sciences. Education is a primary aim of the project; students will be directly involved in the conduct of the studies, and data will be made publicly available.

多巴胺是大脑中一种重要的神经调节剂，参与许多认知过程和行为，例如人们如何做出决定和形成记忆。最近的动物研究表明，多巴胺功能，即多巴胺神经元如何影响大脑活动，比以前认为的更加多样化。 这些动物研究表明，多巴胺的多样性功能不仅仅来自不同类型的多巴胺神经元的存在;相反，它来自大脑中多巴胺系统解剖结构的变化。 不同的多巴胺通路支持不同的认知过程和行为，例如奖励和惩罚，这一点很重要，因为这些通路足够大，可以使用磁共振成像（MRI）等非侵入性技术进行研究。 该项目将在人类参与者中使用MRI来实现两个目标：（1）绘制人类大脑中的多巴胺通路，以及（2）测量多巴胺神经元所在的大脑区域和接受多巴胺输入的大脑区域的活动。这项研究很重要，因为它采用了非侵入性的人类神经成像方法来测试和扩展动物研究的想法。研究人类有希望直接影响和改善对多巴胺介导的行为的理解，这与心理学和社会科学的许多领域广泛相关。因此，该研究项目将有助于更好地了解决策的大脑基础，使人们能够深入了解大脑功能的改变如何影响行为，例如衰老和心理健康障碍。 多巴胺系统参与许多基本的认知和行为过程。到目前为止，多巴胺神经元的子类已经被确定为对奖励，厌恶刺激或同样对奖励和厌恶刺激做出反应。重要的是，最近来自啮齿动物和非人类灵长类动物研究的证据表明，某些多巴胺能通路支持奖励学习和条件性位置偏好，而其他多巴胺能通路支持学习性厌恶和条件性位置回避。总的来说，这一跨越多个实验室和物种的动物研究支持多巴胺系统具有解剖学定义的异质性的观点。该项目旨在验证多巴胺能功能本身是多样的，并且与奖励预测错误的均匀传递不一致的假设。PI将使用功能性磁共振成像（fMRI）和扩散加权图像（DWI）结合概率纤维束成像方法来研究中边缘多巴胺网络的功能和白色物质连接模式，其中包括脑干黑质和腹侧被盖区（SN/VTA），在学习任务期间由奖励和厌恶结果介导。这一奋进值得注意，因为它扩展了脑干的神经成像，包括DWI，它使中脑，纹状体和皮质之间的白色物质连接测量，因为它有可能作出根本性的贡献，决策神经科学如何理解多巴胺介导的行为。这项研究有助于神经经济学的中心目标，这是一个不断发展的跨学科领域，为对神经科学，决策或社会科学感兴趣的本科生和研究生提供了令人兴奋的教育机会。教育是该项目的一个主要目标;学生将直接参与研究的进行，数据将公开提供。