Sensory and learning improvements elicited by oscillatory coupling through local and long-range interneurons

项目摘要 我的长期目标是成为一名成功资助的独立神经生物学家，从事旨在 改善我们对学习和记忆的理解。这一目标将通过实施来实现 高度协调、全面和综合的职业发展计划，包括 指导和培训、熟练的研究环境和补充研究项目。第一，事业 制定了由一名导师和共同导师、课程和会议组成的发展计划，以 为申请者提供过渡到独立职位的技能和指导。这位导师，Dr。 迭戈·雷斯特雷波是一位成功资助的神经科学研究人员和领先专家，也是他的共同导师， 杰米·彼得斯博士在控制学习行为的神经回路方面是公认的领导者，主要是 控制毒品寻求和恐惧，而前额叶皮质在其中起着至关重要的作用。他们非常适合 监督我的训练。指导团队将就职业方面提供批判性的指导和反馈 神经像素高密度电极记录、数据分析和 嗅觉行为任务。指导委员会包括职业生涯不同层次的成员 从年轻教师到高级教师，他们将在与职业直接相关的部分中为申请者提供专门的帮助 过渡。此外，还包括matlab、蟒蛇课程和神经科学会议，以促进 培训计划的这些组成部分。第二，娴熟的研究环境--细胞系 和发育生物学，以及相关的资源、核心设施和 不直接参与申请者咨询委员会的教职员工-成立的目的是提供 申请人成功的保证。第三，已经提出了一个研究项目，以促进我在 令人振奋的新领域对我的独立道路至关重要，同时保持以下关键目标 研究与学习和记忆有关的神经元信号网络。这项研究检验了重要的 改变局部和远程神经元间偶联与CaMKIIα介导可塑性的假说 导致气味增加的PAC的中介变化引发高伽马相的变化 参考功率和在Go-no学习期间解码气味识别的准确率的提高 去做任务吧。AIM 1将评估对局部PV或SST中间神经元或远程的闭环光遗传刺激 以海马或mPFC为靶点的中间神经元在theta峰或通过theta时会引起 振荡耦合使小鼠提高了解码的准确性。AIM 2将评估瞬时中断 靶向mPFC的局部海马区或远程海马区中间神经元CaMKIIα表达改变 从CA1到mPFC的信息传递扰乱了这些小鼠学习 有鉴别力的气味。总体而言，这一全面的职业发展和研究计划将确保我的 成功地从一个独立的研究岗位过渡到准备充分的独立研究岗位。

Project Summary My long-term goal is to become a successfully funded, independent neurobiologist, conducting research aimed at improving our understanding of learning and memory. This goal will be accomplished by the implementation of a highly coordinated, thorough, and integrated career development plan including components of mentored guidance and training, an adept research environment, and a complementary research project. First, a career development plan comprised of a mentor, and co mentors, courses and conferences has been established to provide the applicant with the skills and guidance to transition into a position of independence. The mentor, Dr. Diego Restrepo, is a successfully funded researcher and leading expert in neuroscience and the co-mentor, Dr. Jamie Peters, is a recognized leader in neural circuits controlling learned behaviors, primarily those controlling drug seeking and fear in which the prefrontal cortex plays an essential role. They are well suited to oversee my training. The mentoring team will provide critical guidance and feedback on aspects of career development and technical components high density electrode recording with Neuropixels, data analysis, and olfactory behavior tasks. The mentoring committee includes members at different levels of their career ranging from young to senior faculty who will specifically assist the applicant in components directly related to career transition. In addition, courses in MATLAB, python and conferences on neuroscience are included to facilitate these components of the training program. Second, an adept research environment – the Department of Cell and Developmental Biology at the University of Colorado, along with associated resources, core facilities, and faculty members not directly involved in the applicant’s advisory committee – is established to provide assurance of the applicant’s success. Third, a research project has been proposed to facilitate my training in exciting new areas essential for my path to independence while simultaneously maintaining the key goals of studying neuronal signaling networks as related to learning and memory. The research tests the important hypothesis that altering local and long-range interneuron coupling and CaMKIIα-mediated plasticity mediate changes in PAC that result in an increase in odor elicited change in high gamma phase reference power and an increase in accuracy for decoding odorant identity during learning in the go-no go task. Aim 1 will evaluate Closed loop optogenetic stimulation of local PV or SST interneurons or long-range interneurons targeting hippocampus or mPFC in the peak or through of theta will cause coherence of oscillatory coupling causing the mice to increase decoding accuracy. Aim 2 will evaluate transient disruption of CaMKIIα expression in local SST interneurons or long-range interneurons targeting mPFC causes a change in the transmission of information from the CA1 to mPFC disrupting the ability of these mice to learn to discriminate odorants. Collectively, this comprehensive career development and research plan will ensure my successful transition from a dependent research position into one of well-prepared independence.