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Spatial Codes Across the Medial Entorhinal Cortex for Memory and Navigation

内侧内嗅皮层用于记忆和导航的空间代码

基本信息

批准号：
10120754
负责人：
Lisa Giocomo
金额：
$ 39.81万
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 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10120754
关键词：
Address Back Behavior Behavioral Brain Brain Diseases Brain region Breathing Cells Clinical Code Computer Models Cues Data Development Disease Dissociation Dorsal Electrophysiology (science)Elements Environment Future Goals Ion Channel Lead Learning Left Length Location Maps Medial Memory Mental Depression Mental disorders Modeling Monitor Moods Motor Mus Neurodegenerative Disorders Neurons Neurophysiology - biologic function Pattern Periodicity Play Positioning Attribute Psyche structure Psychiatric therapeutic procedure Resolution Rewards Role Sensory Silicon Spatial Behavior Stimulus Structure Symptoms Translating Visual Weight Work base cell cortex cognitive process computer framework entorhinal cortex experience experimental study improved in vivo insight memory process neural circuit novel public health relevance relating to nervous system response spatial memory virtual environment virtual reality way finding

项目摘要

A central function of the brain is to create internal representations of stimuli and experiences from the outside world to guide behavior. Here, we examine the circuit mechanisms underlying the neural representation of external space, a representation essential to spatial memory and navigation, and impacted by neurodegenerative and psychiatric diseases. The neural basis for the representation of space depends, in part, on circuits in the medial entorhinal cortex, which translate the external environment into an internal map of space. The resolution of the entorhinal neural map of space is topographically organized, with the firing rate tuning curves of spatial and directional neurons progressively increasing along the dorsal to ventral entorhinal axis. This topography has been proposed to allow dorsal versus ventral entorhinal neural codes to support different behaviors, with dorsal regions playing a larger role in spatial learning. While our previous work revealed that the dorsal to ventral gradient in the spatial scale of entorhinal representations impacts spatial memory, the degree to which dorsal versus ventral neural codes for spatial position act as discrete or coordinated circuits to support spatial memory or navigation remains incompletely understood. Here, we propose to combine electrophysiology using silicon probes with spatial and memory tasks in behaving mice. Until now, electrophysiological approaches had to contend with the difficulty of accessing ventral cortical regions and limited recording channel counts, resulting in a lack of studies in which the activity of entorhinal neurons were simultaneously considered across the dorsal- ventral axis. However, new versions of silicon probes have allowed us to record hundreds (>500) of neurons simultaneously along nearly the entire length of mouse entorhinal cortex. This, combined with virtual reality tasks that can rapidly incorporate a diverse set of sensory and non-metric (positive or negative stimuli) cues, will enable us to reveal how neural activity across the dorsal-ventral entorhinal axis is restructured after learning about important environmental features and how this information is then communicated across the entorhinal structure to drive behavior. Achieving significant insight along these fonts will provide a novel understanding of how entorhinal maps of space support spatial memory and navigation.

大脑的一个中心功能是创造来自外部的刺激和经验的内部表征世界引导行为。在这里，我们研究了神经表征的电路机制，外部空间，对空间记忆和导航至关重要的表征，并受到神经退行性疾病的影响，和精神疾病。空间表征的神经基础部分取决于大脑中的回路。内侧内嗅皮层，将外部环境转化为内部空间地图。该决议的内嗅神经地图的空间是地形组织，与放电率调谐曲线的空间定向神经元沿背腹内嗅轴沿着递增。这种地形被提议允许背侧与腹侧内嗅神经代码支持不同的行为，背侧在空间学习中发挥更大作用的区域。虽然我们之前的工作表明，背腹侧内嗅表征的空间尺度的梯度影响空间记忆，背侧表征的程度与腹侧神经编码的空间位置作为离散或协调的电路，以支持空间记忆或导航仍然不完全理解。在这里，我们建议使用硅联合收割机结合电生理学在行为正常的小鼠中进行空间和记忆任务的探测。到目前为止，电生理学方法必须与难以进入腹侧皮层区域和有限的记录通道计数相抗衡，导致缺乏研究，其中内嗅神经元的活动，同时考虑整个背- 腹轴然而，新版本的硅探针使我们能够记录数百（>500）个神经元同时沿着小鼠内嗅皮层的几乎整个长度。这与虚拟现实任务相结合能够快速整合各种感官和非度量（积极或消极刺激）线索，我们揭示了背腹内嗅轴的神经活动是如何重建后，学习重要的环境特征以及这些信息如何通过内嗅结构进行交流 to drive驱动behavior行为.沿着这些字体获得显著的洞察力将提供一种新颖的理解，空间的内嗅图支持空间记忆和导航。