Mechanisms of Neural Synchrony in the Medial Entorhinal Cortex

项目摘要 内侧内嗅皮层（mEC）在空间导航、学习和认知中起着至关重要的作用。 记忆mEC的第II/III层中的许多神经元表现出空间调谐的放电率， 在穿越开阔地时形成的网格状图案。网格细胞的放电率被调制 通过theta（4-12 Hz）频率，通过来自媒体的输入产生的网络范围的振荡 隔膜此外，较高频率的伽马（40-140 Hz）振荡嵌套在较慢的伽马振荡中。 波θ振荡，并被认为有助于同步网格细胞尖峰输出。几 研究表明，网格单元在很大程度上通过密集的网络连接， 快速尖峰的中间神经元，这对产生伽马振荡至关重要。然而，在这方面， 假设的网格细胞和快速发放的中间神经元之间的功能网络连接， 在空间导航期间产生θ嵌套振荡mEC不完全 明白全细胞膜片钳记录仍然是测量细胞内 膜电压和电流，但这种技术具有相对低的通量。最近 荧光电压指示器的进步使得能够对两种动作电位成像 以及在光遗传学刺激期间来自数十个神经元的阈下活动。我们提出 利用全细胞电压钳记录的灵敏度捕获网络突触 在光遗传学刺激期间星状、锥体和快速尖峰中间神经元的活性 不同的局部兴奋性和抑制性细胞群。在此之后，我们将确定 兴奋性和抑制性神经元相对于θ-巢式γ振荡的发放时间 局部场电位通过成像细胞内电压在密集标记的人口， 局部兴奋性神经元的光遗传学刺激。这些技术的结合将 建立开发和测试所需的每种细胞类型的功能输入/输出 在空间导航过程中网格细胞活动和网络同步的潜在规范模型。 拟议的研究将在波士顿大学的Rajen中心进行， 综合生命科学，是神经科学多学科社区的所在地 investigators.该研究所结合了系统神经科学中心的专家， 神经光子学中心，它促进了一个多样化的合作环境，以解决 具有挑战性的研究项目。此外，我的学术培训，技术 技能、科学沟通、专业技能和始终如一的指导将确保 这个项目的成功。

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.