Transformation of Neuronal Activity in the Entorhinal-hippocampal-neocortex Path

内嗅-海马-新皮质路径中神经元活动的转变

• 批准号: 10586043
• 负责人: GYORGY BUZSAKI
• 金额: $ 61.26万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-20 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586043
• 关键词: Affect; Alzheimer' s Disease; Area; Behavior; Brain; Cells; Communication; Coupling; Cytoplasmic Granules; Discrimination; Disease; Electrophysiology (science); Epilepsy; Goals; Hippocampus; Image; Individual; Interneurons; Lateral; Learning; Link; Maps; Maze Learning; Medial; Memory; Neocortex; Neurologic; Neurons; Neurosciences; Parietal Lobe; Pattern; Physiological; Population; Probability; Psyche structure; Pyramidal Cells; Reader; Research Personnel; Rodent; Route; Signal Transduction; Sleep; Stimulus; Structure; Synapses; Testing; Translating; cell assembly; dentate gyrus; entorhinal cortex; experience; experimental study; granule cell; insight; learned behavior; member; neocortical; neuronal circuitry; neuronal patterning; optical imaging; optogenetics; transmission process; vector

SUMMARY What is the right way to investigate neuronal circuits? The dominant strategy in neuroscience is to examine the relationships between stimuli, brain signals and behavior. In this framework, the investigator is in a privileged situation. Because s/he has access to both brain patterns and signals outside the brain, s/he can establish correlations between them. However, without further ‘grounding’, it remains unknown whether these experimenter-observed correlations are actually utilized by the brain. The present project will take an alternative approach by investigating how neuronal population patterns in an upstream circuit are ‘read out’ by a downstream observer circuit/mechanism in memory circuits. Using this strategy, we will investigate how neuronal activity is transformed at each stage in the entorhinal cortex (EC) – dentate gyrus (DG) – CA2/3 – CA1- neocortex loop, and relate such transformations to behavior. The projects will combine large-scale electrophysiology, optogenetics and imaging in behaving rodents. Project 1 will examine the distinct contributions of medial and lateral entorhinal cortex (MEC, LEC) to spatial versus object learning, and will link behavior to EC-DG transmission of theta-gamma oscillatory patterns. Project 2 will examine information transmission within the dentate gyrus and across EC-DG-CA3 synapses. We will first quantify changes in LFP and spike-LFP coupling to test the contributions of EC and DG granule cell input to the firing patterns of DG mossy and CA3 pyramidal cells. We will then test whether DG granule and mossy cell replay is coordinated with hippocampal sharp wave ripples or with EC cell assemblies during post-experience sleep. Finally, we will test whether optogenetic manipulation of dentate spikes affects memory and induces re-configuration of CA3 networks. Project 3 examines whether distinct neuronal trajectories, such as forward and reversed sequences, are read out differentially by target circuits in the CA3-CA1 and CA1-parietal cortical circuits. Finally, Project 4 will test whether different hippocampal patterns are translated to distinct neocortical functional maps and whether such maps are modified by learning. Our ‘reader-centric’ approach will establish how neuronal patterns are transformed in the entorhinal- hippocampal-entorhinal loop, providing critical insights into physiological mechanisms of learning and memory and relevant diseases.

总结 研究神经元回路的正确方法是什么？神经科学的主要策略是 研究刺激、大脑信号和行为之间的关系。在此框架内， 调查员处于特权地位。因为她/他可以接触到大脑模式， 大脑外部的信号，他/她可以建立它们之间的相关性。但如果没有 进一步的“基础”，仍然不知道这些实验观察到的相关性是否 实际上被大脑利用。本项目将采取另一种方法， 研究上游回路中的神经元群体模式是如何被一个 存储器电路中的下游观测器电路/机制。通过这一战略，我们将 研究神经元活动如何在内嗅皮层（EC）的每个阶段转化- 齿状回（DG）-CA 2/3 -CA 1-新皮质环，并将此类转换与 行为这些项目将联合收割机结合大规模电生理学、光遗传学和成像技术， 行为啮齿动物。项目1将检查内侧和外侧的不同贡献 内嗅皮层（MEC，LEC）的空间与对象的学习，并将链接行为EC-DG theta-gamma振荡模式的传输。项目2将审查信息 在齿状回内和跨EC-DG-CA 3突触的传递。我们将首先量化 LFP和尖峰-LFP偶联的变化，以测试EC和DG颗粒细胞的贡献 输入DG苔藓和CA 3锥体细胞的放电模式。然后我们将测试DG是否 颗粒和苔藓细胞的重放与海马尖波波纹或EC相协调 在经历后的睡眠中进行细胞组装。最后，我们将测试光遗传学是否 齿状棘波的操纵影响记忆并诱导CA 3网络的重新配置。 项目3检查不同的神经元轨迹，如向前和向后 序列，由CA 3-CA 1和CA 1-顶叶皮层中的靶回路区别地读出 电路.最后，项目4将测试不同的海马模式是否被翻译为 不同的新皮层功能图，以及这些图是否通过学习而被修改。我们 “以读者为中心”的方法将建立神经元模式是如何在内嗅- 的生理机制提供了重要的见解， 学习和记忆以及相关疾病。