The neural basis of spatial cognition: does neural plasticity in the head direction cell system underlie spatial landmark learning?

当我们漫步在一个熟悉的城镇时，很容易认出我们在哪里，或者指向熟悉的地方。我们之所以能够这样做，是因为我们已经了解了这些地方不同地标之间的关系。例如，爱丁堡的居民通常可以指出他们家的方向，即使它是不可见的，相对于爱丁堡城堡。这项研究的目的是找出学习的地标之间的空间关系发生在大脑中。我们对哺乳动物大脑如何存储空间信息的了解，大部分来自啮齿动物的研究。其中一个大脑结构，海马体，有神经元，当老鼠在它的环境中的特定位置时，它会被激活。这些是定位细胞。另一种类型的神经元位于海马体附近的大脑区域，当老鼠面对一个特定的方向时，它会被激发。这些是头部方向细胞。人们认为，当老鼠在一个熟悉的地方时，位置细胞和头部方向细胞一起使老鼠知道它在哪里。我们的问题是，大脑中哪个区域对位置细胞和头部方向细胞学习识别新环境至关重要？许多形式的空间学习是由海马体中突触连接的变化介导的。例如，通过阻断海马突触可塑性来阻止学习环境中奖励的位置。然而，后下托（PoS），其中发送信息的海马，似乎是必不可少的快速学习和识别环境中的地标。这可能是因为PoS是地标与位置细胞和头部方向细胞相关联的关键部位。然而，这也可能是因为PoS只是一个网站，视觉信息通过它传递到位置细胞和头部方向细胞系统。我们的目的是区分这两种可能性。我们将通过使用一种药物暂时阻断PoS神经元中与学习相关的变化来实现这一目标，这种药物可以阻断突触可塑性，但不会影响正常的突触传递。如果PoS是地标学习的场所，那么在那里阻断可塑性应该有两个效果：a）阻止地标与位置细胞和头部方向细胞的放电之间形成新的关联，以及B）阻止大鼠使用新的地标信息来解决空间记忆任务。这些预测将在拟议的实验中得到检验。如果阻断PoS可塑性会破坏位置细胞、头部方向细胞和空间行为，我们将确定大脑中发生地标学习的部位之一。如果PoS不是大脑中发生里程碑学习的部位，我们将测试邻近的大脑区域，称为压后皮质（RSPL）。RSPL将信息发送到PoS，拥有头部方向细胞，并接收来自接收眼睛输入的大脑部分的输入。在我们看来，PoS或RSPL极有可能是大脑中发生里程碑式学习的部位。无论哪种情况，表明地标学习需要海马体外部的可塑性将是新颖而重要的，因为大多数快速空间学习被认为是由海马体本身介导的。因此，该项目将导致更全面地了解不同的结构如何有助于空间学习和记忆的不同方面。这项研究的好处是，它应该提供有关空间认知的大脑区域的基本信息。我们知道，在一个环境中找到一条路的能力在日常生活中很重要（通常被认为是理所当然的）。然而，这种能力在老年和阿尔茨海默病等疾病中会减弱。了解正常空间认知背后的神经系统是大脑研究中较易处理的问题之一，可能会更好地了解衰老和疾病状态问题的原因。

When we wander through a familiar town, it's easy to recognise where we are or to point in the direction of familiar locations. We are able to do so because we have learned the relationships between different landmarks within these places. For example, residents of Edinburgh can usually point in the direction of their home, even if it is not visible, relative to Edinburgh Castle. The aim of this research is to find out where learning about the spatial relations between landmarks occurs in the brain. Much of what we know about how mammalian brains store spatial information comes from work in rodents. One brain structure, the hippocampus, has neurons that fire when a rat is in a specific place in its environment. These are place cells. Another type of neuron, found in brain areas near the hippocampus, fires when the rat faces a specific direction. These are head direction cells. It is thought that, together, place cells and head direction cells allow the rat to know where it is when it's in a familiar place. Our question is, which brain area is critical for the place cells and head direction cells to learn to recognise new environments? Many forms of spatial learning are mediated by changes in synaptic connections in the hippocampus. For example, learning the location of a reward in the environment is blocked by blocking hippocampal synaptic plasticity. However, the postsubiculum (PoS), which sends information to the hippocampus, appears to be essential for the rapid learning and recognition of landmarks in the environment. This could be because the PoS is the critical site at which landmarks become associated with place cells and head direction cells. However, it could also be because the PoS is simply a site through which visual information passes on its way to the place cell and head direction cell systems. Our aim is to distinguish between these two possibilities. We will do so by temporarily blocking learning-related changes in PoS neurons using a drug that blocks synaptic plasticity, but does not affect normal synaptic transmission. If the PoS is the site of landmark learning, then blocking plasticity there should have two effects: a) to prevent new associations forming between landmarks and the firing of place cells and head direction cells, and b) to prevent the rat from using new landmark information to solve spatial memory tasks. These predictions will be tested in the proposed experiments. If blocking PoS plasticity disrupts place cells, head direction cells and spatial behaviour, we'll have identified one of the sites in the brain where landmark learning takes place. If the PoS is not the site in the brain where landmark learning takes place, we will test an adjacent brain area called the retrosplenial cortex (RSPL). RSPL sends information to the PoS, possesses head direction cells, and receives inputs from parts of the brain that receive inputs from the eyes. In our view, it is extremely likely that either the PoS or the RSPL is the site where landmark learning takes place in the brain. In either case, showing that landmark learning requires plasticity outside the hippocampus would be novel and important, as most rapid spatial learning is thought to be mediated by the hippocampus itself. Thus, this project will lead to a more comprehensive understanding of how different structures contribute to different aspects of spatial learning and memory. The benefit of this research is that it should provide basic information about the brain areas underlying spatial cognition. We know that ability to find one's way around an environment is important in everyday life (and is usually taken for granted). However, this ability can diminish in old age, and in conditions such as Alzheimer's Disease. Understanding the neural systems underlying normal spatial cognition is one of the more tractable questions in brain research, and may yield a better understanding of the cause of problems in aging and disease states.