Alpha6* nAChRs in Dopamine Transmission and Nicotine Dependence

Alpha6* nAChR 在多巴胺传递和尼古丁依赖性中的作用

• 批准号: 8469847
• 负责人: Ryan Michael Drenan
• 金额: $ 22.04万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469847
• 关键词: Address; Adolescent; Adult; Agonist; Animals; Area; Behavior; Behavioral; Biogenesis; Biological; Biology; Birth; Brain; California; Cell physiology; Cells; Cellular Neurobiology; Cellular biology; Cholinergic Receptors; Chronic; Communities; Community Healthcare; Corpus striatum structure; Data; Data Set; Development; Disease; Dopamine; Drug Targeting; Electrophysiology (science); Environment; Event; Exhibits; Faculty; Future; Goals; Growth; Health; Health Services Research; Image; Imagery; Implant; Institutes; Institution; Knock-in Mouse; Knowledge; Label; Laboratories; Learning; Life; Measures; Mediating; Mediator of activation protein; Mentors; Methods; Microscopy; Midbrain structure; Mood Disorders; Mus; Neuraxis; Neurons; Neurosciences; Neurotransmitter Receptor; Neurotransmitters; Nicotine; Nicotine Dependence; Nicotinic Receptors; Occupations; Paper; Parkinson Disease; Pattern; Pharmacotherapy; Phase; Phenotype; Photons; Physiological; Physiology; Positioning Attribute; Predisposition; Presynaptic Receptors; Presynaptic Terminals; Proteins; Publishing; Regulation; Research; Research Personnel; Research Training; Resources; Role; Running; Schizophrenia; Scientist; Secure; Slice; Smoke; Smoker; Techniques; Technology; Testing; Training; Transgenic Mice; Universities; abstracting; cholinergic; design; dopamine system; dopaminergic neuron; drug reinforcement; early adolescence; gain of function; graduate student; multi-photon; mutant; neuronal cell body; neurotransmitter release; novel; osmotic minipump; phase 1 study; postsynaptic; presynaptic; programs; receptor; receptor expression; receptor function; relating to nervous system; research study; selective expression; smoking cessation; stoichiometry; success; trafficking; transmission process

Project Summary/Abstract CANDIDATE My immediate goals are to continue my research and training in electrophysiology, biological imaging and neuroscience. During the K99 phase (2 years), I will conduct experiments and be trained in electrochemical recording methods and multi-photon imaging. I will publish papers and search for a job as an independent faculty/investigator during the K99 phase, and will transition to the R00 independent phase (3 years) upon securing a faculty position. The total duration of the project is 5 years. ENVIRONMENT The K99 phase of this project will be conducted at the California Institute of Technology, which affords an excellent research and learning environment for postdoctoral scientists. Caltech has a strong neuroscience community, excellent faculty, and many highly productive and resourceful postdoctoral scholars and graduate students for one to collaborate with. Caltech also runs the Biological Imaging Center through the Beckman Institute, a resource that will be a very important part of my training plan. For the institution where I will conduct my R00 phase studies, I will choose an institute or university with excellent neuroscience resources and faculty that will put me in the best position for growth and success. RESEARCH This research program is designed to test the hypothesis that specific nicotinic ACh receptors are important for modulating release of neurotransmitters such as dopamine. In particular, I will test the idea that nicotinic receptors containing ¿6 subunits, which are found on dopamine presynaptic terminals, are important mediators of dopamine release. I will also test the idea that the ability of these receptors to mediate dopamine release is governed by their subcellular regulation by the neurons where they reside. Finally, I will test the idea that ¿6 receptor expression and function are significantly altered when animals are exposed to chronic nicotine. Thus, these experiments will determine whether these receptors are important in dopamine release and in disorders such as nicotine dependence. To carry out these experiments, I designed and built a set of novel transgenic mouse lines to particularly isolate aspects of ¿6 nAChR biology. For example, some experiments will utilize mice with hypersensitive ¿6 receptors that amplify and isolate ¿6 physiology and behavior, while other experiments will make use of mice expressing fluorescently-labeled ¿6 receptors that allow for direct visualization of these proteins in live neurons.

项目总结/摘要 候选 我的近期目标是继续我在电生理学，生物成像和 神经科学在K99阶段（2年），我将进行实验并接受电化学培训 记录方法和多光子成像。我将发表论文，并寻找一份独立的工作， 教师/研究员在K99阶段，并将过渡到R 00独立阶段（3年）， 争取教职项目总工期为5年。 环境 该项目的K99阶段将在加州理工学院进行，该学院提供 为博士后科学家提供良好的研究和学习环境。加州理工学院有很强的神经科学 社区，优秀的教师，和许多高生产力和足智多谋的博士后学者和研究生 学生们一起合作。加州理工学院还通过贝克曼运行生物成像中心 研究所，一个资源，这将是一个非常重要的一部分，我的培训计划。在那里我将 进行我的R 00阶段研究，我将选择一个具有优秀神经科学资源的研究所或大学 和教师，这将使我在最好的位置成长和成功。 研究 这项研究计划旨在验证特定的烟碱ACh受体对于 调节神经递质如多巴胺的释放。特别是，我将检验尼古丁 在多巴胺突触前末梢上发现的含有<$6个亚单位的受体是重要的介质 释放多巴胺的能力我还将测试这些受体介导多巴胺释放的能力是 由它们所在的神经元的亚细胞调节来控制。最后，我将测试以下想法： 当动物暴露于慢性尼古丁时，受体表达和功能显著改变。因此，在本发明中， 这些实验将确定这些受体是否在多巴胺释放和疾病中起重要作用。 例如尼古丁依赖。 为了进行这些实验，我设计并建立了一套新的转基因小鼠品系， nAChR生物学的孤立方面。例如，一些实验将利用具有超敏反应的小鼠。 放大和隔离生理和行为的受体，而其他实验将利用小鼠 表达荧光标记的p6受体，允许在活体中直接观察这些蛋白质， 神经元