The use of metric and non metric cues in memory: an investigation using reversal learning in appetitive and non-appetitive tasks

在我们的环境中导航并记住环境中物体位置的能力对生存至关重要。长期以来，人们一直认为位置的变化与海马体中细胞活动的变化有关，海马体是大脑中一个对空间学习和导航很重要的区域。有证据表明，海马体细胞的这种活动受环境的距离和角度/方向特性（公制）以及其他特性（如墙壁颜色和照明）（非公制）的控制。从行为上讲，正是这些相同类型的线索让我们能够区分两种环境。我最近的研究使用了一种反应逆转范式（一只老鼠在t形迷宫中被训练向右转，然后再被训练向左转，这样老鼠就学会了产生记忆干扰的竞争性反应），结果表明，度量属性，尤其是方向，是区分两个位置并允许动物做出特定位置反应的最重要特征。本提案中描述的研究将使用大鼠模型继续研究方向在各种学习任务中的作用，并评估另一个度量属性——距离的作用。这些结果应该让我们了解我们如何利用空间信息来防止形成的记忆之间的干扰。更好地理解基本的记忆过程和干扰记忆提取的因素，使我们能够确定当记忆失败时，哪些过程受到了损害。为了治疗或减缓由阿尔茨海默病和痴呆症（影响海马体的疾病）等疾病引起的记忆衰竭的进展，我们首先需要知道海马体内的细胞如何受到环境线索的影响，以及这如何在行为改变中表现出来。

The ability to navigate in our environment and remember the location of objects in that environment is central to survival. Changes in location have long been correlated with changes in cell activity in the hippocampus, a brain region known to be important for spatial learning and navigation. Evidence suggests that this hippocampal cell activity is controlled by the distance and angle/direction properties of an environment (metric) and other properties such as wall color and lighting (non-metric). These are the same types of cues that allow us, behaviourally, to distinguish between two environments. My recent work, using a response reversal paradigm (a rat is trained to turn right on a T-maze and then subsequently trained to turn left, thus the rat learns competing responses that produce interference between memories), has shown that metric properties, particularly direction, are the most important feature in distinguishing between two locations and allowing an animal to make a location-specific response. The research described in the present proposal will use a rat model to continue to investigate the role of direction in a variety of learning tasks and also to assess the role of another metric property, distance. These results should allow us to understand how we use spatial information to prevent interference between memories that are formed. A better understanding of basic memory processes and factors that interfere with memory retrieval, allows us to determine what processes are compromised when memory fails. In order to treat or slow the progression of memory failure due to such disorders as Alzheimer's disease and dementia (disorders which affect the hippocampus), we first need to know how cells within the hippocampus are influenced by environmental cues and how this manifests itself in behavioral change.