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

动物有惊人的能力知道他们在哪里，并计划去哪里以及如何到达那里。这些 能力可能是基于认知地图，大脑的内部空间表示。50年来， 我已经知道海马位置细胞是认知地图的一个组成部分，当动物受到刺激时， 是在特定的地点。我们还知道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官产生的， 体验.一个难题是感觉输入是“自我中心的”（相对于 个体），而认知地图是“以他者为中心”的（相对于绝对的 世界的参照系）。这就提出了一个关键问题：大脑如何将自我中心的参照 将框架转化为以他为中心的框架来指导行为我们关注的是认知图中代表 边界边界感是动物以自我为中心的体验，但在内侧内嗅皮层（MEC） 和下托复合体，边界由异着丝粒边界细胞（ABC）代表。如果ABC可以 从上游区域的自我中心反应中产生，它们的分配中心性可以传播到其余区域。 通过突触相互作用的认知地图。最近的研究表明，后嗅皮层（POR），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，这些细胞可能编码边界。在目标1中， 我们认为这些是自我中心的边界细胞（EBC），有效地编码方向， 到边界段的距离，如在导航期间主观经历的。我们将测试这个想法， 在不同复杂性的环境中记录自我中心的POR反应，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 提出了一种机制，使POR中的EBC响应结合和分层结合， 头部方向的反应，通过Hebbian可塑性的MEC，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结合神经 录音，我们将从理论模型中得到预测。我们还将进行解剖 研究和失活实验，以测试网络的组件如何连接，以及功能如何 当网络的某些部分被停用时，它会被修改。我们的方法将实现一个重要的里程碑， 揭示电路，大脑区域，以及将感官体验与大脑产生联系起来的机制。 大脑的认知地图，从而为导航和情节记忆缺陷的临床方法提供信息。 相关性（参见说明）： 这项工作将发展一个系统级的理解电路跨大脑区域，支持空间 认知，我们知道我们在哪里和计划我们去哪里的能力。我们必须了解大脑 解决了这样的空间问题，以治疗导航能力的损伤，这是患者的常见缺陷， 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，这项工作也将有助于指导临床方法，这些能力的损害。

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.