Putting episodic memory in context: cellular mechanisms of environmental processing

当我们被要求回忆一件事时，我们通常会描述一件重要的个人事件，如毕业、生日或新工作的第一天。在记忆研究中，对我们生活中特定事件或情节的这些类型的记忆被称为情节记忆。这些记忆影响着我们是什么样的人，以及我们看待自己的方式。我们中的许多人都曾不幸地经历过这种记忆的丧失会如何影响年迈的亲戚。在某些类型的痴呆症中，如阿尔茨海默病(AD)，患者失去了形成新的间歇性记忆的能力。阿尔茨海默病患者可以记住20年前的详细事件，但当被要求回忆当天早些时候发生的事情时，他们会遇到严重的问题。这对他们过独立生活的能力有重大影响。在英国，大约有465000人患有阿尔茨海默病，随着我们社会中老年人比例的增加，这个数字还会增加。据估计，全世界每年花费3380亿英镑为痴呆症患者提供护理和治疗。显然，这是一个需要尽快解决的问题，以减轻NHS和英国纳税人的负担。解决这种疾病的一种方法是检查大脑通常是如何处理情景记忆的，因为这将使我们能够看到在疾病中大脑中的哪些区域和机制出了问题。情节记忆是通过结合事件的特征而形成的。这些包括我们在哪里，我们当时在做什么，以及环境的特点(例如，它是在里面还是外面？)大脑中一个叫做海马体的区域对于整合这些信息非常重要。海马体受损的人在创造新的情节记忆方面存在问题。然而，我们不知道这些不同类型的信息是如何到达海马体的。如果我们能找到大脑中为海马体提供形成情景记忆所需信息的路径，那么我们就可以开始进一步研究这些信息在AD中是如何受到影响的。目前，我们对大脑如何处理空间位置了解很多。在过去的40年里，让我们知道自己所在位置的大脑部分已经被详细描述过了。然而，我们不知道情节记忆的其他部分是如何处理的，比如我们所处的环境的细节。这个应用程序中的实验将通过检查当环境特征发生变化时大脑的哪些部分被激活来解决这个问题。我们将继续观察大脑这些区域的单个细胞对环境变化的反应。我们的具体目标是：1.确定大脑中哪些区域对语境特征的操纵反应活跃，并对提取语境信息的记忆起关键作用。2.确定这些大脑区域中的哪些机制用于处理上下文信息。通过解决这些目标，我们可以更好地理解大脑中处理情景记忆的机制。这将为生产这些疾病的治疗方法的公司提供一个工具，通过在疾病模型中检查这些过程来有效地测试他们的治疗方法。最终，它可能有助于通过帮助为AD提供针对疾病早期阶段的治疗，从而帮助减轻NHS的负担，从而防止发生重大的脑损伤。

When we are asked to think of a memory we will often describe an important personal event such as a graduation, birthday or the first day of a new job. In memory research these types of memories for specific events or episodes from our lives are called episodic memories. These memories influence the kind of people we are and the way that we think about ourselves. Many of us have had the misfortune to experience how the loss of this type of memory can affect an elderly relative. In some types of dementia like Alzheimer's disease (AD) sufferers lose the ability to form new episodic memories. Patients with AD can remember detailed events from 20 years ago but have severe problems when asked to remember what happened to them earlier that day. This has a major impact on their ability to lead independent lives. In the UK approximately 465000 people have AD and this number will increase as the proportion of older people in our society increases. It is estimated that £338 billion pounds each year is spent across the world in providing care and treatment for people with dementia. Clearly this is a problem that needs addressing soon to reduce the burden on the NHS and the UK tax payer. One way to go about tackling the disease is to examine how the brain usually processes episodic memory as this will allow us to see which areas and mechanisms within the brain go wrong in the disease. Episodic memories are formed by combining the features of an event. These include where we were, what we were doing at the time and the features of the environment (e.g. was it inside or outside?). An area of the brain called the hippocampus is important for combining these pieces of information. People who have damage to their hippocampus have problems creating new episodic memories. However, we do not know how these different types of information reach the hippocampus. If we can find out the pathways in the brain that provide the hippocampus with the information that it needs to form episodic memories then we can start to examine further how these are affected in AD. At the moment we know a lot about how the brain processes spatial locations. The parts of the brain that allow us to know where we are have been described in the last 40 years in a lot of detail. However, we do not know how the other parts of episodic memory like the details of the environment in which we were are processed. The experiments in this application will address this problem by examining which parts of the brain are activated when changes to the features of an environment are experienced. We will go on to see how individual cells in these areas of the brain react to changes in the environment. Our specific aims are: 1. To determine which areas of the brain are active in response to the manipulation of contextual features and critical for the retrieval of memory for contextual information. 2. To determine which mechanisms within these brain areas are used to process contextual information. By addressing these aims we well gain a much better understanding of the mechanisms in the brain that process episodic memory. This will provide a tool for companies that produce treatments for these diseases to test their treatments effectively by examining these processes in models of the diseases. Ultimately it may help to reduce the burden on the NHS by helping to provide treatments for AD that target the early stages of the disease and so prevent significant brain damage from occurring.