Mechanisms of Neural Synchrony in the Medial Entorhinal Cortex

内侧内嗅皮层神经同步机制

• 批准号: 10751561
• 负责人: Brandon David Williams
• 金额: $ 3.98万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751561
• 关键词: Academic Training; Action Potentials; Animals; Biological Sciences; Boston; Brain; Cell model; Cells; Communication; Communities; Computer Models; Cortical Synchronization; Data; Development; Electrodes; Ensure; Excitatory Synapse; Exhibits; Feedback; Fostering; Foundations; Frequencies; Gap Junctions; Generations; Home; Image; Interneurons; Intracellular Membranes; Label; Learning; Maps; Measures; Medial; Memory; Mentorship; Modeling; Mus; Neurons; Neurosciences; Output; Pattern; Phase; Physiological; Play; Population; Positioning Attribute; Prevalence; Pyramidal Cells; Recurrence; Research; Research Personnel; Research Project Grants; Role; Slice; Spatial Behavior; Synapses; System; Technical Expertise; Techniques; Testing; Time; Universities; cell type; collaborative environment; entorhinal cortex; excitatory neuron; extracellular; inhibitory neuron; insight; multidisciplinary; neural circuit; neuromechanism; optogenetics; patch clamp; pharmacologic; postsynaptic; redshift; sensor; skills; standard measure; success; voltage; voltage clamp; way finding

Project Summary The medial entorhinal cortex (mEC) plays a vital role in spatial navigation, learning, and memory. Many neurons in layer II/III of the mEC exhibit spatially tuned firing rates that generate a grid-like (‘grid cells’) pattern when traversing an open field. Grid cell firing rates are modulated by a theta (4-12 Hz) frequency, network-wide oscillation generated via input from the medial septum. Further, higher frequency gamma (40-140 Hz) oscillations are nested within the slower- wave theta oscillation and are believed to help synchronize grid cell spike output. Several studies have demonstrated that grid cells are largely connected through a dense network of fast-spiking interneurons which are critical for the generation of gamma oscillations. However, the functional network connectivity between putative grid cells and fast-spiking interneurons in the mEC, which generate theta-nested oscillations during spatial navigation, are not fully understood. Whole-cell patch clamp recordings remain the standard for measuring intracellular membrane voltage and current, but this technique has relatively low throughput. Recent advances in fluorescent voltage indicators have enabled the imaging of both action potentials and subthreshold activity from tens of neurons during optogenetic stimulation. We propose utilizing the sensitivity of whole-cell voltage clamp recordings to capture network synaptic activity in stellate, pyramidal and fast-spiking interneurons during optogenetic stimulation of different local excitatory and inhibitory cell populations. Following this, we will determine the spike timing of excitatory and inhibitory neurons relative to theta-nested gamma oscillations in the local field potential by imaging intracellular voltage in a densely labeled population during optogenetic stimulation of local excitatory neurons. The combination of these techniques will establish the functional input/output of each cell type necessary for developing and testing potential canonical models of grid cell activity and network synchrony during spatial navigation. The proposed research will be conducted at Boston University in the Rajen Center for Integrated Life Sciences which is home to a multidisciplinary community of neuroscience investigators. This institute combines experts from the Center for Systems Neuroscience and the Neurophotonics Center which fosters a diverse collaborative environment to tackle challenging research projects. Further, the development of my academic training, technical skills, scientific communication, professional skills, and consistent mentorship will ensure the success of this project.

项目摘要 内侧肠道皮层（MEC）在空间导航，学习和 记忆。 MEC的II/III层中的许多神经元表现出生成空间调谐的射击率 横穿开放田时，网格样（“网格单元”）模式。网格电池发射率调制 通过theta（4-12 Hz）频率，通过介质输入生成网络范围的振荡 隔膜。此外，较高的频率γ（40-140 Hz）振荡嵌套在较慢的 波theta振荡，被认为有助于同步网格细胞尖峰输出。一些 研究表明，网格细胞在很大程度上通过密集的网络连接 快速刺激的中间神经元对于产生γ振荡至关重要。然而， 推定的网格单元与快速加速的中间神经元之间的功能网络连通性 MEC在空间导航过程中产生theta-nest-nest振荡，尚未完全 理解。全细胞贴片夹记录仍然是测量细胞内的标准 膜电压和电流，但是该技术的吞吐量相对较低。最近的 荧光电压指示器的进步使这两个动作电位都可以成像 在光遗传刺激期间，来自数十个神经元的亚阈值活性。我们建议 使用全细胞电压夹记录的灵敏度捕获网络突触 在光学遗传刺激期间，星状，锥体和快速刺激性的神经元中的活性 不同的局部兴奋性和抑制性细胞群体。之后，我们将确定 兴奋和抑制性神经元相对于theta-nest-nest gamma振荡的尖峰时机 通过在当地标记的人群中成像的局部田间潜力 局部兴奋性神经元的光遗传学模拟。这些技术的结合将 建立开发和测试所需的每种单元格的功能输入/输出 空间导航期间网格细胞活性和网络同步的潜在规范模型。 拟议的研究将在拉詹中心的波士顿大学进行 综合生活科学是神经科学多学科社区的家园 调查人员。该研究所结合了系统神经科学中心的专家 神经音调中心，促进了潜水员协作环境来解决 具有挑战性的研究项目。此外，我的学术培训，技术的发展 技能，科学沟通，专业技能和一致的精通能力将确保 这个项目的成功。