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

• 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
• 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' 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

 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（由申请人提供）：在整个神经系统中，神经输入和输出由高度多样化的离子通道集塑造、调节和整合。值得注意的是，离子通道如何组成神经代码的算法以及这些代码如何转化为行为仍然是神经处理的核心奥秘。在这里，我们的目标是确定离子通道如何控制外部空间的神经表征，这是空间记忆和导航所必需的表征，并受到阿尔茨海默病和抑郁症等神经退行性疾病的影响。空间表征的神经基础部分取决于内侧内嗅皮层的神经回路，它将外部环境转化为内部空间地图。内侧内嗅网格细胞提供了这张地图的神经度量，将行进的距离编码为放电活动的周期性模式， 将整个环境平铺。我以前的工作明确表明，空间选择性内侧内嗅神经元使用离子通道动力学进行空间缩放，使我的实验室前所未有地获得了一个理想的系统，用于研究离子通道底物，编码和行为之间的联系。在这里，我们建议联合收割机在体内电生理学与区域特异性基因操作删除一组离子通道，丢失时，修改内侧内嗅网格细胞的空间表示。我们的数据被解释在多个计算模型的上下文中，使用不同的单细胞属性生成网格编码属性。随后的行为范例将测试离子通道操纵对空间记忆和导航的影响。这些研究将提供重要的见解神经代码和计算的分子基础在高阶皮层区域，并阐明这些计算代码如何影响空间记忆和自我定位的认知过程。