Neurogenetic analysis of value-based decision making

项目总结/摘要 功能失调的决策可能对个人和社会产生破坏性影响。因此，许多类型的决策正在受到积极的调查。该提案强调基于价值的决策， 决策者基于他对选项价值的主观评估在选项中选择哪个选项。对这种行为的深入了解将有助于开发出最好的治疗决策障碍的方法，包括多种形式的成瘾和伴随精神疾病，脑损伤和 神经退行性疾病 消费者选择是基于价值的决策的最佳研究形式之一。经济学家与遗传学家合作发现，我们的经济和性格有着重要的遗传基础， 很难追踪基因和人类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生物，如线虫C。有许多相同的 基因作为人类的基因，基因功能更容易，更便宜，更快地研究。但有证据表明 线虫能够基于价值的决策，在科学意义上，一直缺乏。 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有机体决策的决定因素。在这项提案的初步研究中，PI的实验室开发了 微流控设备，使这项测试能够在线虫上进行，基于食物的选择。试验表明 线虫对食物的质量和价格非常敏感，完全符合基于价值的决策 制作。拟议的研究奠定了多阶段R 01级项目的基石，该项目定义了神经网络。 电路的价值为基础的决策，在线虫，并利用这一知识来调查的功能 人类基因的相互作用与经济决策有关。 该研究首先开发了一种新的高通量测定方法，用于测量 觅食线虫种群的食物选择所提出的测定利用了一种创新的方法，用于制造微型径向臂迷宫。迷宫的每一个分支都将被一个独特的食物选择所吸引， 根据食用菌的浓度和病原菌分泌的天然存在的驱避剂。我们将使用这种方法来确定有关食物和驱虫剂的信息是如何由神经元活动表示的，以及这些表示如何结合起来控制行为。接下来，我们将开始使用遗传方法来鉴定决策电路的过程，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有功能。足以驱动决策的感觉神经元 将被认为是电路的输入神经元。这些知识将加速寻找 在未来的R 01级研究中，电路中的其余神经元。

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.