A neuronal model of memory - integrative processing in the retrosplenial head direction system

理解记忆是当今最重要的科学问题之一，因为记忆丧失的破坏性影响(例如，在阿尔茨海默病？S病中)。记忆生活事件与导航密切相关，因此记忆研究迄今主要集中在空间记忆上。然而，空间记忆是复杂的，进展缓慢。目前的建议旨在开发一个研究更简单版本的空间记忆的研究计划，空间记忆是对指示方向并可用于定向的地标的记忆(例如，当人们从皮卡迪利地下城出来时，可以使用爱神雕像进行定向)。为了在运动中保持定向，有必要将学习到的地标信息与有关自我运动的信息结合起来。里程碑式的学习及其与自我运动信号的结合都被认为发生在被称为脾后皮质(RSC)的大脑区域。与这一想法一致的是，当人们了解新的环境时，RSC变得活跃起来，而这种结构的破坏(例如，中风后)会导致定向障碍和健忘症。本项目将试图了解RSC中标志性记忆是如何形成的，以及它在自我运动过程中是如何更新的。当大鼠学习新的地标，或者当熟悉的地标移动时，将观察单个RSC神经元的活动，以试图确定细胞知道什么信息？关于地标(颜色、形状等)，以及他们是否也知道地标的空间位置，或者仅仅是知道它们的身份。对神经元组的研究将试图确定它们相互影响的程度，而不是受到感官(如视觉)的影响。我们的目标是尝试并确定记忆痕迹？因为新的里程碑式的学习位于RSC，以及它如何与关于运动的信息相互作用。如果该项目成功，RSC将是一个有价值的结构，可以用来研究关于记忆形成的更复杂的问题，比如涉及哪些化学信号，以及如何改善这些过程，例如使用药物。因此，这项工作不仅有助于阐明支持方向感的加工途径，还将有助于更广泛地理解记忆形成和存储的过程，以及如何治疗甚至预防健忘症。

Understanding memory is one of the most important scientific problems today, because of the devastating effects of memory loss (e.g., in Alzheimer?s disease). Remembering life events is closely linked to navigation, and so memory research has hitherto focused on spatial memory. Spatial memory is complex, however, and progress has been slow. The present proposal aims to develop a research programme studying a simpler version of spatial memory, memory for the landmarks that indicate directional heading and can be used to orient (such as one might orient using the statue of Eros, when emerging from the Piccadilly Underground). To remain oriented during movement, it is necessary to combine learned landmark information with information about self-motion. Both landmark learning and its combination with self-motion signals are thought to take place in a brain region known as retrosplenial cortex (RSC). Consistent with this idea, RSC becomes active when people learn about new environments, and damage to this structure (e.g., following stroke) causes both disorientation and amnesia. The present project will try to understand how landmark memory is formed in RSC, and how it is updated during self-motion. The activity of single RSC neurons will be observed while rats learn about new landmarks, or when familiar landmarks are moved, to try and determine what information the cells ?know? about the landmarks (colour, shape etc) and whether they also know about the spatial position of landmarks, or simply about their identity. Studies of groups of neurons will try to determine the extent to which they influence each other, as opposed to be influenced by the senses (such as vision). The goal is to try and determine whether the ?memory trace? for new landmark learning is located in RSC, and how this interacts with information about movement. If the project is successful, the RSC will be a valuable structure with which to pursue more complex questions about memory formation, such as what chemical signals are involved, and how these processes might be improved, for example with drugs. Thus, this work will not only help elucidate the processing pathways underpinning the sense of direction, but will also contribute more broadly to an understanding of the processes by which memories are formed and stored, and of how amnesia might be treated or even prevented.