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.

项目摘要 /摘要 功能失调的决策可能会对个人和社会产生毁灭性的影响。因此，许多类型的决策都受到了积极的调查。该提议强调基于价值的决策， 选择者根据其对价值的主观评估在期权中选择。对这种行为的更深入了解将有助于开发决策障碍的最佳治疗方法，包括多种形式的成瘾和精神疾病，脑损伤和伴随的认知缺陷 神经退行性疾病。 消费者选择是研究最佳的基于价值的决策形式之一。经济学家与遗传学家合作发现，我们的经济性我们的个性具有重要的遗传基础，但这是 很难追踪人类基因与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，例如线虫蠕虫秀丽隐杆线虫，它具有许多相同的 基因作为人类，其中基因功能更容易，更便宜，更快。但是证明了这一点 在科学意义上，线虫具有基于价值的决策，缺乏基于价值的决策。 经济学家已经开发了严格的测试程序，以确定主观价值是否是生物决策中的决定因素。在该提案的初步研究中，PI的实验室开发了 可以根据食物选择对线虫进行此测试的微流体设备。测试表明 线虫以完全一致的方式对食物的质量和价格敏感 制作。拟议的研究为定义神经的多相R01级项目奠定了基石 线虫中基于价值的决策的电路，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。 该研究首先开发了一种新的高通量测定法，以测量 觅食线虫种群中的食物选择。拟议的测定法利用一种创新方法来制造微型径向臂迷宫。迷宫的每个手臂都将被定义的独特食物选择。 可食用细菌的浓度和致病细菌分泌的天然驱虫剂的术语。我们将使用这种方法来确定神经元活动如何代表有关食物和驱虫剂的信息，以及如何将这些表示形式组合为控制行为。接下来，我们将开始使用遗传方法来识别决策电路的过程，以创建线虫菌株，其中 五个食物检测的感觉神经元中只有一个功能性。感觉神经元足以推动决策 制造将被认为是电路的输入神经元。这些知识将加速搜索 未来R01级研究中电路中的其余神经元。