Alpha6* nAChRs in Dopamine Transmission and Nicotine Dependence

项目摘要/摘要 候选人 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方面的培训 记录方法和多光子成像。我会发表论文，找一份独立的工作 K99阶段的教员/研究人员，并将过渡到R00独立阶段(3年) 确保一个教员的职位。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了良好的研究和学习环境。加州理工大学拥有强大的神经科学 社区，优秀的教师，以及许多高生产率和足智多谋的博士后学者和研究生 学生作为一个合作伙伴。加州理工学院还通过Beckman运营生物成像中心 学院，这将是我培训计划中非常重要的一部分。对于我将在那里的机构 进行R00阶段的学习，我会选择拥有优秀神经科学资源的学院或大学 和教职员工，这将使我处于成长和成功的最佳位置。 研究 这项研究计划旨在检验以下假设：特定的尼古丁ACh受体对 调节神经递质的释放，如多巴胺。特别是，我将测试尼古丁的想法 在多巴胺突触前终末发现的含有6个亚单位的受体是重要的介体 多巴胺的释放。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进行亚细胞调控。最后，我将测试一下这个想法。 当动物长期接触尼古丁时，受体的表达和功能会发生显著变化。因此， 这些实验将确定这些受体是否在多巴胺释放和紊乱中起重要作用。 比如尼古丁依赖。 为了进行这些实验，我设计并建立了一套新的转基因小鼠系，以特别是 分离nAChR生物学的各个方面。例如，一些实验将利用患有过敏症的小鼠。 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6受体，允许在活体中直接观察这些蛋白质 神经元。

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.