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， 我们对学习和记忆的理解。这一目标将通过实施 高度协调、全面和综合的职业发展计划，包括 指导和培训，一个熟练的研究环境，和一个互补的研究项目。第一，职业生涯 制定了由一名导师、多名共同导师、课程和会议组成的发展计划， 为申请人提供过渡到独立职位的技能和指导。导师，博士。 Diego Restrepo是一位成功资助的研究人员，也是神经科学领域的领先专家， 博士杰米·彼得斯是控制习得行为的神经回路的公认领导者，主要是那些 控制药物寻求和恐惧，其中前额叶皮层起着重要作用。它们非常适合于 监督我的训练辅导小组将提供有关职业方面的重要指导和反馈 开发和技术组件使用Neuropixels进行高密度电极记录，数据分析， 嗅觉行为任务。指导委员会包括不同职业水平的成员， 从年轻到高级教师，他们将在与职业直接相关的部分专门帮助申请人 过渡此外，还包括MATLAB，Python和神经科学会议的课程，以促进 培训计划的这些组成部分。第二，一个熟练的研究环境-细胞系 和发育生物学在科罗拉多大学，沿着相关的资源，核心设施， 教师不直接参与申请人的咨询委员会-成立提供 确保申请人的成功。第三，一个研究项目已经提出，以促进我的培训， 令人兴奋的新领域对我的独立之路至关重要，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。这项研究测试了 改变局部和远程中间神经元耦联和CaMKIIα介导的可塑性的假说 介导PAC的变化，导致气味增加，引起高γ相的变化 参考能力和在进行中的学习期间解码气味剂身份的准确性的增加 执行任务。目的1将评估局部PV或SST中间神经元或长距离PV或SST中间神经元的闭环光遗传学刺激。 在theta峰或through中靶向海马或mPFC的中间神经元将引起 振荡耦合导致小鼠增加解码准确性。目标2将评估 局部SST中间神经元或靶向mPFC的长程中间神经元中的CaMKIIα表达导致 从CA 1到mPFC的信息传递破坏了这些小鼠学习的能力， 辨别气味。总的来说，这个全面的职业发展和研究计划将确保我的 成功地从一个依赖的研究位置转变为一个准备充分的独立。

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.