CRCNS: US-Israel - The egocentric-allocentric transformation of the cognitive map

CRCNS：美国-以色列 - 认知地图的自我中心-非中心转变

• 批准号: 10227807
• 负责人: Vijay Balasubramanian
• 金额: $ 25.69万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227807
• 关键词: Anatomy; Animals; Area; Behavior; Brain; Cells; Clinical; Code; Cognition; Cognitive; Complex; Computer Models; Confusion; Data; Dementia; Echolocation; Environment; Episodic memory; Generations; Geometry; Head; Hippocampal Formation; Hippocampus (Brain); Impairment; Individual; Instruction; Investigation; Israel; Learning; Light; Location; Maps; Measures; Medial; Modeling; Neurons; Neurosciences; Output; Patients; Population; Research; Rest; Sensory; Synapses; System; Techniques; Temporal Lobe; Testing; Theoretical model; Touch sensation; Tracer; Trauma; Vibrissae; Vision; Weight; Work; anatomical tracing; base; cell cortex; entorhinal cortex; experience; experimental study; impaired capacity; insight; novel; relating to nervous system; response; sensory input; statistics; theories

Animals have the striking ability to know where they are, and to plan where to go and how to get there. These abilities are likely based on a cognitive map, the brain’s internal representation of space. For 50 years we have known that hippocampal place cells are a component of the cognitive map, responding when an animal is in specific locations. We also know about other components of the map – e.g., grid cells, head-direction cells, and border cells. But we do not understand how the responses of such cells are generated from sensory experience. One puzzle is that sensory inputs are “egocentric” (centered and oriented in relation to the individual), whereas the cognitive map is “allocentric” (centered and oriented in relation to an absolute reference frame in the world). This raises a key question: how does the brain transform egocentric reference frames into allocentric ones to guide behavior? We focus on the part of the cognitive map representing boundaries. Boundaries are experienced egocentrically by animals, but in the medial entorhinal cortex (MEC) and the subicular complex, borders are represented by allocentric boundary cells (ABCs). If ABCs can be generated from egocentric responses in upstream areas, their allocentricity could be propagated to the rest of the cognitive map via synaptic interactions. Recent work shows that the postrhinal cortex (POR), a principal area projecting to the MEC, contains cells with egocentric responses that may encode boundaries. In Aim 1, we propose that these are Egocentric Boundary Cells (EBCs) that efficiently encode orientations and distances to boundary segments, as subjectively experienced during navigation. We will test this idea by recording egocentric POR responses in environments of varying complexity, while testing the tuning of responses to spatial boundaries, and comparing to predictions of efficient coding theory. In Aim 2 we further propose a mechanism whereby EBC responses in POR are conjunctively and hierarchically combined with head-direction responses through Hebbian plasticity in the MEC, to produce ABC responses. We will test this mechanism through environmental manipulations and confusion experiments combined with neural recordings, for which we will have predictions from theoretical models. We will also perform anatomical studies and inactivation experiments to test how components of the network connect, and how functionality is modified when some parts of the network are inactivated. Our approach will achieve a significant milestone, uncovering circuits, brain areas, and mechanisms connecting sensory experience to the generation of the brain’s cognitive map, thus informing clinical approaches to deficits in navigation and episodicmemory. RELEVANCE (See instructions): This work will develop a systems-level understanding of circuits across brain areas that underpin spatial cognition, our ability to know where we are and to plan where we go. We must understand how the brain solves such spatial problems to treat impairment of the ability to navigate, a common deficit in patients with early stage dementia or temporal lobe trauma. As spatial cognition is closely tied to episodic memory and abstract navigation, this work will also help to guide clinical approaches to impairment of these capacities.

动物具有惊人的能力，知道它们在哪里，并计划去哪里以及如何到达那里。这些 能力可能基于认知图，即大脑对空间的内部表示。 50年来我们 我们知道海马位置细胞是认知图的一个组成部分，当动物 位于特定位置。我们还了解地图的其他组成部分——例如网格单元、头部方向 细胞和边界细胞。但我们不明白这些细胞的反应是如何从感觉产生的 经验。一个谜题是感觉输入是“以自我为中心的”（以自我为中心和导向） 个体），而认知地图是“异中心的”（以绝对的关系为中心和导向） 世界参考系）。这就提出了一个关键问题：大脑如何改变以自我为中心的参照 框架变成非中心框架来指导行为？我们关注认知地图中代表的部分 边界。动物以自我为中心体验边界，但位于内侧内嗅皮层 (MEC) 和下皮复合体，边界由异中心边界细胞（ABC）表示。如果 ABC 可以 由上游区域的自我中心反应产生，它们的非中心性可以传播到其他区域 通过突触相互作用来绘制认知图。最近的研究表明，鼻后皮质（POR）是一个主要的 投射到 MEC 的区域包含具有自我中心反应的细胞，这些反应可能编码边界。在目标 1 中， 我们认为这些是自我中心边界细胞（EBC），可以有效地编码方向和 到边界段的距离，如导航期间主观体验的那样。我们将通过以下方式测试这个想法 在不同复杂度的环境中记录以自我为中心的 POR 响应，同时测试 对空间边界的响应，并与有效编码理论的预测进行比较。在目标 2 中，我们进一步 提出一种机制，使 POR 中的 EBC 响应与 通过 MEC 中的 Hebbian 可塑性进行头部方向反应，产生 ABC 反应。我们将测试 这种机制通过环境操纵和混淆实验与神经网络相结合 记录，我们将从理论模型中进行预测。我们还将进行解剖学 研究和失活实验，以测试网络组件如何连接以及功能如何 当网络的某些部分被停用时会被修改。我们的方法将实现一个重要的里程碑， 揭示将感官体验与生成神经元联系起来的回路、大脑区域和机制 大脑的认知图，从而为导航和情景记忆缺陷的临床方法提供信息。 相关性（参见说明）： 这项工作将对跨大脑区域的电路形成系统级的理解，这些电路是空间的基础 认知，我们知道自己在哪里并计划去哪里的能力。我们必须了解大脑是如何 解决此类空间问题以治疗导航能力受损，这是患有以下疾病的患者的常见缺陷 早期痴呆或颞叶创伤。由于空间认知与情景记忆密切相关 抽象导航，这项工作还将有助于指导针对这些能力损伤的临床方法。