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

基本信息

批准号：
10819013
负责人：
GYORGY BUZSAKI
金额：
$ 6.09万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/10819013
关键词：
Affect Anatomy Area Automobile Driving Axon Behavior Behavioral Biotechnology Brain Cells Code Cognitive deficits Coupling Cues Cytoplasmic Granules Data Data Analyses Dendrites Disease Disinhibition Distal Electroencephalography Electrophysiology (science)Episodic memory Fiber Foundations Frequencies Glutamates Goals Hippocampus Image Individual Interneurons Knowledge Lateral Learning Link Location Maps Medial Mediating Memory Mental Depression Mental disorders Monitor Mus Neocortex Neurons Neurosciences Neurosciences Research Optics Output Parents Parietal Lobe Pathway interactions Patients Pattern Performance Phase Photometry Physiological Play Population Post-Traumatic Stress Disorders Pyramidal Cells Reader Research Personnel Rodent Role Schizophrenia Sensory Signal Transduction Sleep Stimulus Structure Synapses Techniques Testing Time Training Translating Viral Work career cell assembly dentate gyrus entorhinal cortex experience field study granule cell hippocampal pyramidal neuron in vivo insight memory encoding memory recall multisensory neocortical neural neuronal circuitry neuronal patterning optogenetics recruit segregation skill acquisition transmission process

项目摘要

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 entorhinalhippocampal-entorhinal loop, providing critical insights into physiological mechanisms of learning and memory and relevant diseases.

调查神经元电路的正确方法是什么？神经科学的主要策略是检查刺激，大脑信号和行为之间的关系。在这个框架中，调查人员处于特权状况。因为他/她可以访问这两种大脑模式和大脑外的信号可以建立它们之间的相关性。但是，没有进一步的“基础”，这些专家观察到的相关性是否是未知的实际上是由大脑使用的。本项目将采用另一种方法调查上游电路中的神经元种群模式是如何通过内存电路中的下游观察者电路/机制。使用此策略，我们将研究如何在内嗅皮层（EC）的每个阶段转化神经元活性 - 齿状回（DG） - Ca2/3 - Ca1-新皮层环，并将此类转换与行为。这些项目将结合大规模的电生理学，光遗传学和成像行为啮齿动物。项目1将研究媒体的不同贡献和后来的贡献 entorhinal Cortex（MEC，LEC）到空间与对象学习，并将行为链接到EC-DG theta-gamma振荡模式的传播。项目2将检查信息齿状回和EC-DG-CA3突触内的传播。我们将首先量化 LFP和SPIKE-LFP耦合的变化以测试EC和DG颗粒细胞的贡献输入DG苔藓和CA3锥体细胞的发射模式。然后，我们将测试是否DG 颗粒和苔藓细胞重放与海马尖锐波浪或EC协调体验后睡眠期间的细胞组件。最后，我们将测试是否光学遗传齿状尖峰的操作会影响记忆并引起CA3网络的重新配置。项目3检查了明显的神经元轨迹，例如向前和反转序列是由CA3-CA1和CA1-顶皮质中的目标电路差异读取的界。最后，项目4将测试是否将不同的海马模式转化为独特的新皮层功能图以及是否通过学习修改了此类地图。我们的 “以读者为中心”的方法将确定神经元模式如何在 intorhinalhinalhimpocampal- entorhinal循环，为生理机制提供了关键的见解学习，记忆和相关疾病。