Lateral Entorhinal Cortex (LEC) and episodic memory: examining LEC's impact on pattern separation and neurogenesis

外侧内嗅皮层 (LEC) 和情景记忆：检查 LEC 对模式分离和神经发生的影响

基本信息

批准号：
BB/X007197/1
负责人：
James Ainge
金额：
$ 70.53万
依托单位：
University of St Andrews
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FX007197%2F1
关键词：
Lateral Entorhinal Cortex LEC episodic

项目摘要

Episodic memory is a fundamental cognitive process. Our episodic memories include details of specific objects or people, spatial locations and contextual details that allow us to differentiate between one event and another. A key feature of episodic memory is that it integrates the features of events to help guide future behaviour. For example, an episodic memory of where we parked our car this morning will allow us to accurately locate the car when we need to go home. Damage to an area of the brain called the hippocampus produces an inability to form new episodic memories. Our own recent work has shown that one of the main inputs to the hippocampus from lateral entorhinal cortex (LEC) is also necessary to integrate the features of an event pointing towards a key role for this LEC-hippocampus network in episodic memory. However, the circuit mechanisms within this network that integrate this information are unknown. One of the main targets for LEC input to hippocampus is the dentate gyrus (DG) subfield. DG is one of a small number of regions in the brain where newborn neurons are generated every day in a process called neurogenesis. These newborn neurons have been shown to be important for simple forms of memory such as fear conditioning, specifically for a process called pattern separation which allows us to discriminate between similar stimuli. However, the role of these newborn neurons and pattern separation in distinguishing between different episodic memories for very similar events is unknown. As a critical next step we will test the hypothesis that neurogenesis mediates pattern separation of similar episodic memories in the hippocampus supported by input from LEC. We will test predictions from this hypothesis through 3 specific aims:Aim 1: To determine whether newborn neurons facilitate pattern separation in tests requiring integration of the features of episodic memory.Aim 2: To determine whether LEC inputs to DG mediate the number of newborn neurons and pattern separation in tests requiring integration of EM features. Aim 3: To determine whether neurogenesis affects pattern separation in hippocampal place cells during tests requiring integration of episodic memory features.We anticipate wide reaching impact of this research. Episodic memory is affected by lifestyle factors such as diet, exercise and cognitive stimulation and decline in episodic memory is the first symptom of Alzheimer's disease. Understanding the neural mechanisms that support episodic memory will give specific targets to researchers interested in maintaining healthy cognitive function through the lifespan as well as those attempting to develop therapeutic strategies for disorders of memory. We also anticipate impact in the reduction of the number of laboratory animals needed in memory studies. In the last 5 years an estimated 43000 animals were used in studies of object recognition, the basis of all of the behavioural tasks in the current application. The proposed research will examine how enriched environments could improve memory performance in these animals. Improved performance would increase statistical power and mean that fewer animals would be needed to study these types of memory. Given the number of animals involved uptake by only 5% of the research community could mean thousands fewer animals being used in research.

情节记忆是一个基本的认知过程。我们的情节记忆包括特定对象或人的详细信息，空间位置以及上下文细节，使我们能够区分一个事件和另一个事件。情节记忆的一个关键特征是它集成了事件的功能，以帮助指导未来的行为。例如，对我们今天早上停放汽车的偶发记忆将使我们在需要回家时准确地定位汽车。对大脑区域的损害称为海马会产生形成新的情节记忆。我们自己最近的工作表明，从外侧内嗅皮层（LEC）中海马的主要输入之一也是集成事件的特征，指向该LEC-Hippocampus网络在情节内存中的关键作用。但是，该网络中集成此信息的电路机制尚不清楚。 Hippocampus LEC输入的主要目标之一是齿状回（DG）子场。 DG是大脑中少数区域之一，在称为神经发生的过程中，每天都会产生新生神经元。这些新生神经元已被证明对于简单的记忆形式（例如恐惧调节）很重要，特别是对于一种称为模式分离的过程，该过程使我们能够区分相似的刺激。但是，这些新生神经元和模式分离在区分非常相似事件的不同情节记忆中的作用尚不清楚。作为下一步的关键，我们将检验以下假设：神经发生介导了LEC输入支持的海马中相似情节记忆的模式分离。我们将通过3个特定目的从该假设中测试预测：目标1：确定新生儿神经元是否促进了在需要整合情节内存特征的测试中分离的模式分离。IAM2：确定DG的LEC输入是否介导了新生神经元的数量和需要在需要EM特征集成的测试中的新生神经元的数量和模式分离。目标3：确定神经发生在需要集成情节记忆特征的测试过程中是否会影响海马放置细胞中的模式分离。我们预计这项研究会产生广泛的影响。情节记忆受到生活方式因素的影响，例如饮食，运动和认知刺激以及情节记忆的下降是阿尔茨海默氏病的第一个症状。了解支持情节记忆的神经机制将为有兴趣通过寿命维持健康的认知功能以及试图制定记忆障碍治疗策略的研究人员提供特定的目标。我们还期望对记忆研究中所需的实验动物数量减少产生影响。在过去的5年中，估计有43000只动物用于对象识别的研究，这是当前应用中所有行为任务的基础。拟议的研究将研究丰富的环境如何改善这些动物的记忆力。提高的性能将增加统计能力，这意味着研究这些类型的记忆将需要更少的动物。鉴于只有5％的研究界涉及的动物数量可能意味着在研究中使用的动物少数千。