The Ionic Basis of Spatial Codes in Medial Entorhinal Cortex

内侧内嗅皮层空间编码的离子基础

基本信息

批准号：
9321962
负责人：
Lisa Giocomo
金额：
$ 39.35万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-25 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9321962
关键词：
Adult Algorithms Alzheimer&apos s Disease Behavior Behavioral Behavioral Paradigm Biophysics Brain Brain region Cardiovascular system Cells Code Computer Simulation Cyclic AMP Data Disease Dorsal Electrophysiology (science)Elements Environment Epilepsy Genes Geometry HCN1 channel HCN1 gene Impairment Ion Channel Kinetics Knock-out Lead Left Light Location Maps Medial Memory Mental Depression Methods Molecular Mood Disorders Mus Nervous system structure Neuraxis Neurodegenerative Disorders Neurons Neurophysiology - biologic function Output Pattern Performance Periodicity Plasticizers Primates Process Property Prosencephalon Resolution Rodent Role Scheme Shapes Signal Transduction Symptoms System Technology Testing Translating Travel Viral Work base biophysical properties cell cortex cognitive process entorhinal cortex experimental study genetic manipulation in vivo insight memory process memory recall neural circuit neuroregulation novel public health relevance relating to nervous system response scale up sensory input spatial memory way finding

Adult Algorithms Alzheimer&apos s Disease Behavior Behavioral Behavioral Paradigm Biophysics Brain Brain region Cardiovascular system Cells Code Computer Simulation Cyclic AMP Data Disease Dorsal Electrophysiology (science)Elements Environment Epilepsy Genes Geometry HCN1 channel HCN1 gene Impairment Ion Channel Kinetics Knock-out Lead Left Light Location Maps Medial Memory Mental Depression Methods Molecular Mood Disorders Mus Nervous system structure Neuraxis Neurodegenerative Disorders Neurons Neurophysiology - biologic function Output Pattern Performance Periodicity Plasticizers Primates Process Property Prosencephalon Resolution Rodent Role Scheme Shapes Signal Transduction Symptoms System Technology Testing Translating Travel Viral Work base biophysical properties cell cortex cognitive process entorhinal cortex experimental study genetic manipulation in vivo insight memory process memory recall neural circuit neuroregulation novel public health relevance relating to nervous system response scale up sensory input spatial memory way finding

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项目摘要

DESCRIPTION (provided by applicant): Throughout the nervous system, neural inputs and outputs are shaped, tuned and integrated by highly diversified sets of ion channels. Remarkably, how ion channels compose the algorithms of neural codes and how these codes translate into behavior remain central mysteries of neural processing. Here, we aim to determine how ion channels control the neural representation of external space, a representation essential to spatial memory and navigation, and impacted by neurodegenerative diseases such as Alzheimer's disease and depression. The neural basis for the representation of space depends, in part, on neural circuits in the medial entorhinal cortex, which translate the external environment into an internal map of space. Medial entorhinal grid cells provide the neural metric of this map, encoding distance traveled as a periodic pattern of firing activity that tiles the entire environment. My previous work explicitly demonstrated that spatially selective medial entorhinal neurons use ion channel kinetics for spatial scaling, giving my lab unprecedented access to a system ideal for studying the connections between ion channel substrates, coding and behavior. Here, we propose to combine in vivo electrophysiology with region specific gene manipulations to delete the set of ion channels that, when lost, modify medial entorhinal grid cell spatial representations. Our data is interpreted in the context of multiple computational models, which use different single-cell properties to generate grid coding properties. Subsequent behavioral paradigms will test the effects ion channel manipulations have on spatial memory and navigation. These studies will provide important insights into the molecular underpinnings of neural codes and computations in a high-order cortical region and elucidate how these computational codes impact the cognitive processes of spatial memory and self-localization.

描述（由适用提供）：通过神经系统，神经发射和输出由高度多样化的离子通道组成，调整和整合。值得注意的是，离子通道如何构成神经元代码的算法以及这些代码如何转化为行为仍然是神经元处理的核心奥秘。在这里，我们旨在确定离子通道如何控制外部空间的神经元表示，这是空间记忆和导航必不可少的代表，并受到神经退行性疾病（例如阿尔茨海默氏病和抑郁症）的影响。空间表示的神经元基础部分取决于内侧内嗅皮层中的神经信号，将外部环境转化为内部空间图。培养基网格细胞提供了该地图的神经计量学，编码距离的距离是发射活动的周期性模式瓷砖整个环境。我以前的工作明确表明，空间选择性培养基内嗅神经元使用离子通道动力学进行空间缩放，这使我的实验室前所未有地访问系统，非常适合研究离子通道基板，编码和行为之间连接的系统。在这里，我们建议将体内电生理学与区域特定基因操作相结合，以删除一组离子通道，这些离子通道会在丢失时会改变培养基内嗅网格细胞的空间表示。我们的数据是在多个计算模型的上下文中解释的，这些计算模型使用不同的单细胞属性来生成网格编码属性。随后的行为范式将测试离子通道操纵对空间内存和导航的影响。这些研究将为高阶皮质区域中神经代码和计算的分子基础提供重要的见解，并阐明这些计算代码如何影响空间记忆和自定位的认知过程。