Vector Trace cells in the Subiculum of the hippocampal formation

众所周知，海马体支持空间记忆、导航、规划和想象力。了解海马体如何支持这些功能是全球密集、高调研究的主要目标。在这里，我们关注的是一种特殊的空间记忆：记住定义空间的线索位于多远和哪个方向。这被称为矢量记忆，我们认为它对海马体的功能至关重要。理论和经验研究表明，广义地说，空间映射依赖于两种感觉输入：一种来自自我运动线索，一种来自外部环境线索。关于自我运动，我们可以通过估计我们已经移动了多远以及朝着什么方向来了解我们所处的位置，例如，根据运动和感觉系统通知我们的活力、所走的步数和步幅的程度等线索。当然，我们周围的空间并不是空的，而是充满了各种外部线索，比如边界、物体和目标(就像主场一样)。为了有效导航，动物还必须编码这些定义空间的外部线索位于多远和哪个方向。路径规划和想象等认知过程需要记忆这种向量表征的能力，但缺乏证据表明有神经元可以提供这种向量记忆。重要的是，我们最近发现了正是这种向量记忆的证据：一种新的神经元类型，我们称之为矢量跟踪细胞(VTC)，位于海马结构的下丘脑区。VTC会在对象被移走后数小时内记住该对象的距离和方向。我们怀疑至少有一些VTC可以记住这一点几天，我们将对此进行测试。VTC似乎为计算动物和多个线索(或不同线索)之间的空间关系提供了记忆，摆脱了必须直接感知这些线索的限制。与不能记住这些空间关系的系统相比，这可以实现更强大的空间规划和想象力认知。事实上，我们推测可能有一些认知功能并不是明显的空间功能，但依赖于多个维度的矢量编码，如果输入的是语言信息，VTC可以支持这些功能。显然，如果我们想确切地了解海马体如何支持空间记忆、导航、规划和想象力，这是全球广泛研究的，那么我们需要了解海马体如何产生基于矢量的空间记忆。如果不了解下丘脑的特殊贡献，就不可能做到这一点。我们在下丘脑中发现了矢量追踪细胞，它是海马结构的关键输出区。至少在人类中，它可能是与大脑其他部分相互作用的最关键的海马区，这个网络被称为“默认模式网络”。自传式记忆、创造性思维、白日做梦、想象力以及面向未来的推测和计划都被认为高度依赖于这种“默认模式网络”。我们怀疑，基于矢量的认知和记忆支持这些更广泛的基于记忆的和创造性的功能。这项资助旨在通过深入了解以下内容来改变对海马体向量编码的理解：下丘如何在功能上组织成不同的部分，其中一个部分支持向量记忆；单个向量踪迹细胞如何产生向量编码以及形成和维持向量记忆的机制，以及这种记忆持续多长时间；以及外部线索的向量编码如何影响依赖于自我运动的时刻活动的空间映射。

It is well established that the hippocampus supports spatial memory, navigation, planning, and imagination. Understanding how the hippocampus supports these functions is a major goal of intense, high-profile research globally. Here, we focus on a particular kind of spatial memory: remembering how far away and in what direction space-defining cues are located. This is called vector memory, and we think it is crucial to hippocampal function.Theoretical and empirical work has indicated that spatial mapping relies, broadly speaking, on two kinds of sensory inputs: one derived from self-motion cues, one from external environmental cues. Regarding self-motion, we can get some idea of where we are by estimating how far we have moved and in what direction, for instance from clues such as the motor and sensory systems informing us of the vigour and number of strides taken, and the degree of stride extension. Of course, the spaces around us are not 'empty', but filled with various external cues such as boundaries, objects and goals (like home bases). To navigate effectively, an animal must also encode how far away and in what direction such space-defining external cues are located. Cognitive processes such as path-planning and imagination entail the ability to remember such vector representations, but evidence that there are neurons that can provide such vector memory has been lacking.Importantly, then, we have recently found exactly such evidence of vector memory: a novel neuron type, which we call the Vector Trace cell (VTC), located in a region of the hippocampal formation called the subiculum. VTCs remember the distance and direction to an object for hours after that object is removed. We suspect that at least some VTCs can remember this for days, which we will test. It seems likely that VTCs provide memories for computing the spatial relationships between an animal and multiple cues (or between different cues), freed from the constraints of having to directly perceive those cues. This enables more powerful spatial planning and imaginative cognition than would be the case for a system that could not remember these spatial relationships. Indeed we speculate there might be some cognitive functions that are not obviously spatial, but rely on vector coding in more than one dimension, that VTCs could support, if the input to them was for example verbal information.Clearly, if we want to understand exactly how hippocampus supports spatial memory, navigation, planning, and imagination, which is intensively researched globally, then we will need to understand how the hippocampus produces vector-based spatial memory. This cannot be achieved without appreciating the particular contribution of the subiculum, where we have discovered Vector Trace cells, and which is a key output region of the hippocampal formation. In humans at least, it may be the most crucial hippocampal region for interacting with the rest of the brain in a network called the 'default mode network'. Autobiographical memories, creative thought, daydreaming, imagination and future-oriented speculation and plans are all thought to be highly dependent upon this 'default mode network'. We suspect that vector-based cognition and memories support these wider memory-based and creative functions. This grant aims to deliver a step-change in the understanding of hippocampal vector coding by delivering insights into: how the subiculum is organised functionally into different divisions, with one of these divisions supporting vector memory; the mechanisms of how individual vector trace cells generate vector coding and form and maintain vector memories, and how long this memory lasts; and finally how vector coding of external cues influences spatial mapping that is reliant, for its moment-to-moment activity, on self-motion.