Grid Cell Dynamics During Navigation In Virtual Reality

虚拟现实导航过程中的网格单元动态

基本信息

批准号：
8422165
负责人：
DAVID W TANK
金额：
$ 39.43万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-26 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8422165
关键词：
Address Alzheimer&apos s Disease Animals Behavior Behavioral Behavioral Paradigm Calcium Cell model Cells Characteristics Cues Degenerative Disorder Disease Employee Strikes Environment Episodic memory Excision Fire - disasters Frequencies Head Hippocampus (Brain)Histologic Image Information Theory Intracellular Membranes Length Link Location Maps Measurement Medial Membrane Membrane Potentials Mental disorders Methods Metric Modeling Motion Mus Neurons Optics Pattern Phase Population Positioning Attribute Property Ramp Reporting Resolution Rodent Role Schizophrenia Sensory Series Staining method Stains Surface System Techniques Technology Temporal Lobe Epilepsy Testing Thinking Time Training Visual awake base behavior measurement calcium indicator cell type cellular imaging cognitive function cytochrome c oxidase entorhinal cortex insight interest neural circuit neural model novel operation optical imaging patch clamp reconstruction relating to nervous system research study response two-photon virtual virtual reality voltage

项目摘要

DESCRIPTION (provided by applicant): The medial entorhinal cortex (MEC) contributes to navigation and episodic memory, essential cognitive functions degraded in many degenerative and psychiatric disorders. A key to MEC function was provided by the discovery of grid cells, which fire on the vertices of a set of hexagonal lattices tessellating space. The grid cell system has been hypothesized to perform path integration during navigation and to be a map of the spatial environment. Because of the striking regularity of their firing fields, grid cells have generated widespread theoretical interest, and numerous models have been proposed to explain how grids are formed, how they are organized in microcircuits, and how they might use idiothetic (self motion) information to path integrate. The grid cell system therefore offers the opportunity to study a cognitively meaningful neural computation at a mechanistic level. Here we leverage recent technical advances, including virtual reality methods for rodents previously developed in our lab, to examine the intracellular, microcircuit, and integrative properties of gri cells in three aims: 1.) Current grid cell models can reproduce hexagonal lattice firing patterns but they predict different intracellular membrane potential time courses that reflect different underlying cellular or network mechanisms. To test these predictions, in Aim 1, we will take advantage of head-fixed navigation enabled by our virtual reality system to make intracellular recordings from grid cells during behavior. Statistical analysis will be performed on the membrane voltage time series to examine if characteristic features such as ramps and theta oscillations are present and if they correlate with the location of the firing fields. For example,we will examine if theta oscillation amplitude is larger in firing fields, and if theta frequency increases with mouse velocity, as predicted by theta interference models of grid cells. 2.) Grid cells are not identical, but have different scales and phase shifts that may reflect distinct functional modules. Consistent with this idea, converging evidence points to the existence of anatomically defined clusters of cells in MEC. To delineate the link between functional modules and anatomical clusters, in Aim 2 we will use cellular-resolution two-photon calcium imaging during virtual navigation to provide the first measurements of spatial organization, at the microcircuit scale, of identified grid cells in MEC. In particular, we will map the relationship between grid cell properties (spatial scale and phase) and cytochrome oxidase rich patches, and determine whether there are sharp breaks in spatial scale along the dorsoventral axis. 3.) Grid cells are thought to perform path integration, an idea that dominates the current thinking about the functional role of the MEC. In Aim 3 we will use virtual reality to control all sensory cues providing information about position in order to rigorously test the path integration hypothesis. Together, these aims should advance our understanding of the single-cell, microcircuit, and computational properties of grid cells. PUBLIC HEALTH RELEVANCE: Using electrophysiological and behavioral methods, we will examine the mechanisms by which the medial entorhinal cortex establishes a metric representation of the environment. Many diseases are associated with functional disruption of the entorhinal cortex and hippocampus, such as Alzheimer's disease, schizophrenia, and temporal lobe epilepsy. The proposed experiments will address the fundamental mechanisms of neural circuit dynamics, generating insight into the normal operation of the entorhinal cortex and how it may be altered in disease.

描述（由申请人提供）：内侧内嗅皮层（MEC）有助于导航和情节记忆，基本认知功能在许多退化性和精神疾病中降低。通过发现网格单元，它在一组六角形晶格镶嵌空间的顶点上发射了MEC功能的关键。已经假设网格电池系统在导航过程中执行路径积分，并成为空间环境的地图。由于其射击场的显着规律性，网格细胞已经产生了广泛的理论兴趣，并提出了许多模型来解释网格的形成，如何在微电路中组织的方式以及如何使用惯用（自动运动）信息来集成路径。因此，网格细胞系统提供了在机械级别研究认知有意义的神经计算的机会。在这里，我们利用了最近的技术进步，包括以前在实验室中开发的啮齿动物的虚拟现实方法，以检查三个目标中GRI细胞的细胞内，微电路和整合性特性：1。）当前的网格细胞模型可以繁殖六角形的晶格触发模式，但它们可以预测不同细胞内膜的潜在时间的电池或网络中不同的网络机构，这些时间均不同。为了测试这些预测，在AIM 1中，我们将利用虚拟现实系统启用头部固定导航，以在行为过程中从网格单元中进行细胞内记录。统计分析将在膜电压时间序列上进行，以检查是否存在诸如坡道和theta振荡之类的特征，以及它们是否与射击场的位置相关。例如，我们将检查theta振荡幅度在射击场中是否较大，以及theta频率是否随着小鼠速度的增加而增加，如网格细胞的Theta干扰模型所预测的那样。 2.）网格细胞并不相同，但具有不同的尺度和相移可能反映了不同的功能模块。与这个想法一致，融合证据表明MEC中细胞的解剖簇存在。为了描述功能模块与解剖簇之间的联系，在AIM 2中，我们将在虚拟导航期间使用细胞分辨率的两光子钙成像，以在MEC中以微电路量表为单位组织进行空间组织的首次测量。特别是，我们将绘制网格细胞性质（空间尺度和相）与细胞色素氧化酶富含斑块之间的关系，并确定沿背腹轴的空间尺度上是否存在急剧断裂。 3.）网格细胞被认为执行路径积分，这一想法主导了当前对MEC功能作用的思维。在AIM 3中，我们将使用虚拟现实来控制提供有关位置信息的所有感官提示，以便严格检验路径集成假设。总之，这些目标应提高我们对网格细胞的单细胞，微电路和计算特性的理解。公共卫生相关性：使用电生理和行为方法，我们将检查内侧内hin骨皮质建立环境的度量表示的机制。许多疾病与内嗅皮层和海马的功能破坏有关，例如阿尔茨海默氏病，精神分裂症和颞叶癫痫。提出的实验将解决神经回路动力学的基本机制，从而深入了解内嗅皮层的正常运行以及如何改变疾病。