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

通过局部和远程中间神经元的振荡耦合引起感觉和学习的改善

• 批准号: 10640975
• 负责人: Daniel Ramirez-Gordillo
• 金额: $ 20.59万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640975
• 关键词: Acute; Address; Advisory Committees; Affect; Animals; Area; Association Learning; Axon; Behavior; Behavioral; Brain; Brain region; Ca(2+)-Calmodulin Dependent Protein Kinase; Calmodulin; Career Mobility; Caring; Cells; Cellular biology; Colorado; Communication; Core Facility; Coupling; Data; Data Analyses; Development Plans; Developmental Biology; Discrimination; Disease; Distant; Drug Controls; Electrodes; Ensure; Environment; Faculty; Feedback; Frequencies; Fright; Funding; Goals; Hippocampus; Individual; Interneuron function; Interneurons; Knockout Mice; Lead; Learning; Life; Link; Long-Term Depression; Long-Term Potentiation; Medial; Mediating; Memory; Mentors; Mus; Neurons; Neurosciences; Odors; Olfactory Learning; Parvalbumins; Performance; Phase; Phosphotransferases; Play; Population; Positioning Attribute; Prefrontal Cortex; Pythons; Research; Research Personnel; Research Project Grants; Resources; Respiration; Rewards; Role; Sensory; Signal Transduction; Somatostatin; Testing; Training; Training Programs; Universities; Virus; Wild Type Mouse; Work; awake; calmodulin-dependent protein kinase II; career; career development; density; experimental study; improved; learned behavior; mature animal; member; neural circuit; neurotransmission; olfactory bulb; optogenetics; research and development; senior faculty; sensory integration; skills; success; symposium; transmission process

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.

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，进行针对的研究 提高我们对学习和记忆的理解。实施将实现此目标 由高度协调，彻底且综合的职业发展计划，包括Mattered的组成部分 指导和培训，熟练的研究环境以及一个完整的研究项目。首先，职业 已经建立了精神和联合会，课程和会议的发展计划 为申请人提供过渡到独立立场的技能和指导。导师博士 迭戈·雷斯特雷普（Diego Restrepo）是一位成功的资助研究员，是神经科学和联合学者的领先专家， 杰米·彼得斯（Jamie Peters）博士是控制学习行为的神经回路的公认领导者，主要是 控制药物和恐惧，前额叶皮层起着至关重要的作用。他们非常适合 监督我的培训。心理团队将为职业方面提供关键的指导和反馈 开发和技术成分高密度电极记录，使用神经偶像，数据分析和 嗅觉行为任务。心理委员会包括其职业生涯不同级别的成员 从年轻的教师到高级教师，他们将专门为申请人提供与职业直接相关的组成部分 过渡。此外，包括Matlab，Python和关于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，熟练的研究环境 - 细胞系 以及科罗拉多大学的发展生物学，以及相关的资源，核心设施和 不直接参与申请人咨询委员会的教职员工旨在提供 保证申请人的成功。第三，提出了一个研究项目，以促进我的培训 令人兴奋的新领域对于我的独立道路至关重要，同时保持 研究与学习和记忆有关的神经元信号网络。研究测试重要 假设改变了局部和远距离的间神经元耦合以及CAMKIIα介导的可塑性 介导PAC的变化，从而导致气味升高引起高γ相变化 参考功率和在学习过程中解码异常身份的准确性提高 去任务。 AIM 1将评估局部PV或SST中间神经元或远距离的闭环光遗传学模拟 靶向海马或MPFC峰或theta的中间神经元将导致连贯性 振荡耦合导致小鼠提高解码精度。 AIM 2将评估瞬态中断 靶向MPFC的局部SST中间神经元或远程神经元中的CAMKIIα表达会导致变化 信息从CA1传输到MPFC，破坏了这些小鼠学会学会的能力 区分气味。总的来说，这个全面的职业发展和研究计划将确保我 从依赖的研究地位成功过渡到准备充分的独立性之一。