Neurogenetic analysis of value-based decision making

基于价值的决策的神经遗传学分析

• 批准号: 9227202
• 负责人: SHAWN R LOCKERY
• 金额: $ 22.04万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9227202
• 关键词: Accounting; Adopted; Afferent Neurons; Animal Model; Bacteria; Behavior; Behavior Control; Behavioral; Behavioral Genetics; Biological Assay; Biological Models; Brain Injuries; Caenorhabditis elegans; Cognitive deficits; Collaborations; Comorbidity; Complex; Data; Decision Analysis; Decision Making; Disease; Economic Models; Economics; Etiology; Exhibits; Food; Foundations; Future; Genes; Genetic; Genetic Epistasis; Genetic Models; Health; Heritability; Human; Individual; Invertebrates; Investigation; Knowledge; Laboratories; Link; Mathematics; Measures; Mental disorders; Methodology; Methods; Microfluidic Microchips; Modeling; Nematoda; Neurodegenerative Disorders; Neurons; Organism; Orthologous Gene; Palate; Pathway interactions; Pattern; Personality; Persons; Population; Price; Procedures; Process; Psychology; Radial; Research; Research Proposals; Resolution; Rest; Social Welfare; Societies; Taste Perception; Testing; Time; Transgenic Organisms; Work; addiction; arm; base; biological systems; economic behavior; gene function; gene interaction; genetic analysis; genetic approach; genome annotation; genome wide association study; high throughput analysis; high throughput screening; improved; innovation; interest; mutant; neural circuit; neurogenetics; neuronal circuitry; neurophysiology; novel; pathogenic bacteria; preference; sensory integration; trait

PROJECT SUMMARY / ABSTRACT Dysfunctional decision making can have devastating impacts on individuals and on society. Many types of decision making are therefore under vigorous investigation. This proposal emphasizes value-based decisions, in which the chooser selects among options based on his subjective assessment of their value. A deeper understanding of this behavior will help to develop the best possible treatments for decision making disorders, including the many forms of addiction and the cognitive deficits that accompany mental illness, brain injury, and neurodegenerative disease. Consumer choice is one of the best studied forms of value-based decisions. Economists, in collaboration with geneticists, have found that our economic our personalities have a significant genetic basis, but it is difficult to trace causal links between genes and behavior in humans. To overcome this problem, many geneticists turn to simpler invertebrate organisms like the nematode worm C. elegans which has many of the same genes as humans and in which gene function is much easier, cheaper, and faster to study. But evidence that nematodes are capable of value-based decision making, in a scientifically meaningful sense, has been lacking. Economists have developed rigorous testing procedures for determining whether subjective value is the deciding factor in an organism's decisions. In preliminary research for this proposal, the PI's laboratory developed microfluidic devices that enable this test to be done on nematodes based on food choices. The tests show that nematodes are sensitive to the quality and price of food in a manner fully consistent with value-based decision making. The proposed research lays the cornerstone for a multiphase R01-level project that defines the neural circuit for value-based decision making in nematodes and exploits this knowledge to investigate the functional interactions of human genes known to be associated with economic decisions. The research begins by developing a new, high-throughput assay for measuring the subjective value of food options in populations of foraging nematodes. The proposed assay utilizes an innovative method for fabricating miniature radial arm mazes. Each arm of the maze will be baited with a unique food option defined in terms of the concentration of edible bacteria and a naturally occurring repellent secreted by pathogenic bacteria. We will use this approach to determine how information about food and repellents is represented by neuronal activity, and how these representations are combined to control behavior. Next, we will begin the processes of identifying the decision making circuit using a genetic approach to create nematode strains in which only one of the five food-detecting sensory neurons is functional. Sensory neurons sufficient to drive decision making will be considered to be the input neurons of the circuit. This knowledge will accelerate the search for the rest of the neurons in the circuit in future R01-level research.

项目概要/摘要 功能失调的决策可能会对个人和社会产生毁灭性影响。因此，许多类型的决策正在接受严格的调查。该提案强调基于价值的决策， 选择者根据其对价值的主观评估在选项中进行选择。更深入地了解这种行为将有助于开发治疗决策障碍的最佳疗法，包括多种形式的成瘾以及伴随精神疾病、脑损伤和 神经退行性疾病。 消费者选择是基于价值的决策中研究最充分的形式之一。经济学家与遗传学家合作发现，我们的经济和性格具有重要的遗传基础，但它是 很难追踪人类基因和行为之间的因果关系。为了克服这个问题，许多遗传学家转向更简单的无脊椎动物生物，例如线虫秀丽隐杆线虫，它具有许多相同的特征 基因就像人类一样，并且基因功能的研究更容易、更便宜、更快捷。但有证据表明 从科学意义上讲，线虫一直缺乏基于价值的决策能力。 经济学家已经制定了严格的测试程序来确定主观价值是否是有机体决策的决定因素。在该提案的初步研究中，PI 实验室开发了 微流体装置使该测试能够根据食物选择对线虫进行。测试表明 线虫对食物的质量和价格很敏感，其方式与基于价值的决策完全一致 制作。拟议的研究为定义神经网络的多阶段 R01 级项目奠定了基石 线虫基于价值的决策电路，并利用这些知识来研究功能 已知与经济决策相关的人类基因的相互作用。 该研究首先开发一种新的高通量测定法来测量主观价值 觅食线虫种群的食物选择。所提出的测定方法利用一种创新方法来制造微型径向臂迷宫。迷宫的每个臂都将用定义在中的独特食物选项作为诱饵 就可食用细菌的浓度和病原菌分泌的天然驱虫剂而言。我们将使用这种方法来确定有关食物和驱虫剂的信息如何通过神经元活动来表示，以及如何将这些表示结合起来来控制行为。接下来，我们将开始使用遗传方法识别决策电路的过程，以创建线虫菌株，其中 五个食物检测感觉神经元中只有一个是有功能的。感觉神经元足以驱动决策 将被视为电路的输入神经元。这些知识将加速寻找 电路中的其余神经元将在未来的 R01 级研究中进行。