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，或者指着熟悉的位置。我们之所以能够做到这一点，是因为我们了解了这些地方不同地标之间的关系。例如，相对于爱丁堡城堡，爱丁堡的居民通常可以指向他们家的方向，即使它看不见。这项研究的目的是找出学习地标之间的空间关系在大脑中发生在哪里。我们所知道的关于哺乳动物大脑如何存储空间信息的大部分知识来自啮齿动物的工作。海马体是一种大脑结构，当大鼠处于环境中的特定位置时，它的神经元会被激发。这些是Place细胞。另一种类型的神经元，发现于海马体附近的大脑区域，当老鼠面对特定方向时会发出信号。这些是头部方向的细胞。据认为，当老鼠在熟悉的地方时，放置细胞和头部方向细胞一起让老鼠知道它在哪里。我们的问题是，位置细胞和头部方向细胞学习识别新环境的关键是大脑的哪个区域？许多形式的空间学习是通过海马区突触连接的变化来调节的。例如，通过阻止海马体突触的可塑性，学习奖赏在环境中的位置被阻止。然而，将信息发送到海马体的下丘后(Pos)似乎对快速学习和识别环境中的地标是必不可少的。这可能是因为POS是界标变得与位置单元和头部方向单元相关联的关键位置。然而，这也可能是因为POS仅仅是视觉信息通过其传递到位置单元和头部方向单元系统的场所。我们的目标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做到这一点，这种药物可以阻断突触的可塑性，但不会影响正常的突触传递。如果POS是标志性学习的场所，那么阻止那里的可塑性应该有两个效果：a)防止地标与位置细胞和头部方向细胞的激发之间形成新的联系，以及b)防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验证。如果阻止位置可塑性扰乱位置细胞、头部方向细胞和空间行为，我们就已经确定了大脑中发生里程碑式学习的位置之一。如果pos不是大脑中发生里程碑式学习的地方，我们将测试邻近的大脑区域，称为脾后皮质(Rspl)。RSPL向POS发送信息，拥有头部方向细胞，并接受来自大脑从眼睛接收输入的部分的输入。在我们看来，POS或RSPL极有可能是在大脑中进行里程碑式学习的场所。在任何一种情况下，表明里程碑式的学习需要海马体外的可塑性将是新颖和重要的，因为大多数快速空间学习被认为是由海马体本身调节的。因此，这个项目将导致对不同结构如何有助于空间学习和记忆的不同方面的更全面的理解。这项研究的好处是它应该提供关于空间认知的大脑区域的基本信息。我们知道，在日常生活中找到周围环境的路的能力很重要(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可能会减弱。了解正常空间认知背后的神经系统是大脑研究中比较容易处理的问题之一，可能会更好地理解衰老和疾病状态下问题的原因。

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.