BRAIN EAGER: Novel Thermo-genetic Tools for Extrinsic Control of Neuronal Circuits

BRAIN EAGER：用于神经元回路外部控制的新型热遗传工具

• 批准号: 1535790
• 负责人: Troy Zars
• 金额: $ 30万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1535790&HistoricalAwards=false
• 关键词: BRAIN; EAGER; Novel; Thermo; genetic

Brains can be thought of as networks of circuits. The neurons that make up these circuits interact to control behavior, but how the neurons do this is currently an open question. New tools are needed to learn how neuron networks produce behavior. One promising strategy would be to construct molecular switches that could flip neurons between active and inactive states. This project will investigate the potential to engineer a special group of proteins to make them serve as molecular switches that respond to changes in temperature. The proteins will be put into specific brain neurons of flies, and the fly's behaviors will be monitored in response to temperature changes that activate and deactivate the neurons. The fly is an accessible experimental model for these studies, and, additionally, what is learned in the fly brain will have broad relevance to other animal brains. The project will involve undergraduate and graduate students in the research and will provide them with interdisciplinary training in biophysics, neurophysiology, and behavior. Tools developed in the project have the potential to be used to understand other organ systems and will be shared with the wider scientific community. Individual Gustatory Receptor (GR) gene family members will be examined for temperature-dependent effects on nerve cell function. In one set of experiments, these GRs will be expressed in both sensory and non-sensory neurons in Drosophila melanogaster and tested for temperature responsiveness in heat-box behavioral assays. In a second set of experiments, natural- and chimeric-GRs will be expressed in Xenopus oocytes and COS cells and tested for temperature- and voltage-dependent kinetics of ionic current. Finally, natural- and chimeric-GRs will be expressed in sensory neurons in Drosophila and cultured cells and examined for physiological effects using live calcium imaging analysis.

可以将大脑视为电路网络。 构成这些电路的神经元可以控制行为，但是神经元如何执行此操作是一个悬而未决的问题。 需要新的工具来了解神经元网络如何产生行为。 一种有希望的策略是构建可以在活性和无活性状态之间翻转神经元的分子开关。 该项目将调查设计一种特殊的蛋白质的潜力，以使它们充当分子开关，以响应温度的变化。蛋白质将被放入苍蝇的特定脑神经元中，苍蝇的行为将根据激活和失活神经元的温度变化而受到监测。 苍蝇是这些研究的无障碍实验模型，此外，苍蝇中所学的东西将与其他动物大脑具有广泛的相关性。 该项目将涉及本科生和研究生参与研究，并将为他们提供生物物理学，神经生理学和行为的跨学科培训。 项目中开发的工具有可能用于了解其他器官系统，并将与更广泛的科学界共享。 将检查单个味觉受体（GR）基因家族成员对温度依赖性对神经细胞功能的影响。 在一组实验中，这些GRS将在果蝇果蝇中的感觉和非感官神经元中表达，并在热盒行为测定中测试了温度响应性。 在第二组实验中，自然和嵌合-gr将在爪蟾卵母细胞和COS细胞中表达，并测试了离子电流的温度和电压依赖性动力学。 最后，自然和嵌合-gr将在果蝇和培养细胞中的感觉神经元中表达，并使用实时钙成像分析检查生理效应。

项目成果

Working Memory: It’s a Gas, Gas, Gas

工作记忆：它是气体、气体、气体

• DOI: 10.1016/j.cub.2017.01.005
• 发表时间: 2017
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Zars, Troy

Sex: The End Is All You Need

性：结束就是你所需要的

• DOI: 10.1016/j.cub.2018.04.013
• 发表时间: 2018
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Mishra, Aditi;Zars, Troy
• 通讯作者: Zars, Troy