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Spatial coding in the hippocampal formation: boundaries and grids

海马结构的空间编码：边界和网格

基本信息

批准号：
BB/M008975/1
负责人：
Colin Lever
金额：
$ 51.05万
依托单位：
Durham University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FM008975%2F1
关键词：
Spatial coding hippocampal formation boundaries

项目摘要

Memory is central to our everyday lives, and make us who we are. An area of the brain called the hippocampal formation (HF) is crucial to some of the most useful memories we have (those that tell us where to find the people we care about, the food we want to eat, the places that promise excitement, and where to avoid places we might be scared of); and crucial to our most treasured memories (those memories of the events of our lives, such as first kisses, weddings, births, and deaths, that give us our identity and humanity). It turns out that the HF is crucial for a kind of spatial memory called allocentric spatial memory. Allocentric refers to large-scale or 'map-like' space, which is defined with reference to the environment as opposed to egocentric space, which is defined in relation to sensory organs like your retina and skin, and in relation to motor effectors like your limbs. Briefly, egocentric representations are crucial for behaviours such as catching a ball or picking fruit from a tree; but behaviours such as remembering the location of water-sources, and navigating long distances over natural terrain also require allocentric, map-like, representations. The hippocampal formation is also crucial for memory that relies on a representation of a context, such as episodic memory (for the events of our lives). It may be that the hippocampus provides a spatiotemporal context to which the contents of a memory (a bride, a mother, their seat locations, the chicken, bad jokes) can be bound. We know that the HF is crucial for these kinds of memories from many types of evidence, notably that patients with damaged hippocampi don't find their way about well, and can't easily form new episodic memories. Our sense of location & context is likely driven by HF 'place cells', that is, neurons which fire in context-dependent, specific locations. This sense-of-place derives from: 1) self-motion cues, and; 2) external environmental cues. 'Grid cells', which fire in a very geometric tile-like way throughout all environments, represent self-motion information. Like human A-Z atlases, tiling out equal-sided squares over town streets & buildings, the mammalian brain tiles out broadly-equilateral triangles over environments. The recent discovery by our research team of boundary vector cells. which fire when an environmental boundary (e.g. walls, drop-offs) is located at a specific distance & allocentric direction from the subject, supplied the crucial missing piece in understanding the environmental cue contribution. So we seem to know about neurons which establish spatial location based on our own movements, and about neurons which establish our spatial location based on where we are in relation to our surroundings. What we now need is a broad, systems-level understanding of how the representation of environmental boundaries is organised in the HF, and how boundary cells interact with other spatial cells. We go about this by recording a lot of individual neurons and also local field potentials (informing us about brain waves). To help us further manipulate particular subsets of neurons, while we record, we beam laser light at neurons that have been genetically modified to be affected (excited, inactivated) by laser light at particular frequencies. To be able to manipulate external environmental cues in a controlled way, we also employ Virtual Reality. We want to explore particular anatomical circuits in the HF, focusing on regions called the subiculum, which may be an organizing centre for boundary representations, and the entorhinal cortex and CA1, which are both strongly connected to the subiculum. We want to test our new ideas about how the subiculum is organised, and how it might provide boundary-related information to the HF. Our work is focused on spatial cognition and memory, but we hope to reveal general principles of the neural representation and organization of episodic memory.

记忆是我们日常生活的核心，是记忆成就了我们。大脑中有一个叫做海马体形成（HF）的区域对我们拥有的一些最有用的记忆至关重要（这些记忆告诉我们在哪里可以找到我们关心的人，我们想吃的食物，哪里会让人兴奋，哪里会让我们害怕）；对我们最珍贵的记忆（那些关于我们生活中事件的记忆，比如初吻、婚礼、出生和死亡，这些赋予了我们身份和人性）至关重要。事实证明，高频对一种叫做非中心空间记忆的空间记忆至关重要。异中心空间指的是大尺度或“地图般的”空间，它是参照环境来定义的，而不是以自我为中心的空间，它是根据感觉器官（如视网膜和皮肤）以及运动效应器（如四肢）来定义的。简而言之，自我中心表征对于诸如接球或从树上摘水果等行为至关重要；但是，诸如记住水源的位置以及在自然地形上长距离导航等行为也需要非中心的、类似地图的表示。海马体的形成对于依赖于环境表征的记忆也至关重要，比如情景记忆（关于我们生活中的事件）。这可能是因为海马体提供了一个时空背景，记忆的内容（新娘、母亲、她们的座位位置、鸡、坏笑话）可以与之联系在一起。我们从许多证据中知道HF对这类记忆至关重要，特别是海马体受损的患者无法很好地找到自己的路，也不能轻易形成新的情景记忆。我们对位置和环境的感觉很可能是由HF“位置细胞”驱动的，即在依赖于环境的特定位置放电的神经元。这种空间感来源于：1)自我运动线索；2)外部环境线索。“网格细胞”在所有环境中以非常几何的瓷砖状方式发射，代表自我运动信息。就像人类的A-Z地图集，在城镇街道和建筑物上平铺出等边正方形，哺乳动物的大脑在环境上平铺出宽等边三角形。我们的研究小组最近发现了边界载体细胞。当环境边界（如墙壁，斜坡）位于特定距离和非中心方向时，它就会触发，这为理解环境线索的贡献提供了关键的缺失部分。所以我们似乎知道神经元根据我们自己的运动来确定空间位置，也知道神经元根据我们与周围环境的关系来确定空间位置。我们现在需要的是对高频中环境边界的表示是如何组织的，以及边界细胞如何与其他空间细胞相互作用有一个广泛的、系统级的理解。我们通过记录大量单个神经元和局部场电位（告诉我们脑电波）来做到这一点。为了帮助我们进一步操纵特定的神经元子集，在我们记录的同时，我们将激光照射到经过基因改造的神经元上，这些神经元会受到特定频率激光的影响（激发，灭活）。为了能够以可控的方式操纵外部环境线索，我们还采用了虚拟现实技术。我们想要探索HF中特定的解剖回路，重点关注被称为耻骨下的区域，这可能是边界表征的组织中心，以及内嗅皮层和CA1，它们都与耻骨下紧密相连。我们想测试我们关于下骨是如何组织的新想法，以及它如何为HF提供与边界相关的信息。我们的工作重点是空间认知和记忆，但我们希望揭示情景记忆的神经表征和组织的一般原理。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Frequency matters: how changes in hippocampal theta frequency can influence temporal coding, anxiety-reduction, and memory.

DOI：
10.3389/fnsys.2022.998116
发表时间：
2022
期刊：
FRONTIERS IN SYSTEMS NEUROSCIENCE
影响因子：
3
作者：
Hines, Miranda;Poulter, Steven;Douchamps, Vincent;Pibiri, Francesca;McGregor, Anthony;Lever, Colin
通讯作者：
Lever, Colin

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice

弥散张量 MRI 和 CLARITY 的受试者体内应用揭示了 Nrxn2 缺失小鼠的大脑结构变化