PROJECT 1-Neural encoding based on lateral and medial entorhinal information processing streams in behaviorally-characterized aged rats

海马体和内侧颞叶是大脑陈述性记忆系统的重要组成部分。 对这些结构的广泛破坏导致毁灭性和永久性地丧失形成新的能力， 对事实和个人经历的有意识的记忆。年龄与年龄的丧失或变化密切相关 记忆功能，在正常衰老和神经病理条件下都是如此。外侧内嗅觉皮质 内侧颞叶皮质(LEC)和内侧内嗅皮层(MEC)提供了内侧颞叶的绝大部分输入 海马体。MEC似乎向海马体提供了一个关于一个人的空间位置的信号 有机体。这种信号被认为是一个框架，允许海马体将 在空间和时间的某一时刻发生的体验的各个组成部分。此框架允许 海马体形成一个连贯的表征，它被存储起来，然后作为情节记忆被检索出来。这个 LEC在这一体系中的作用还鲜有人探讨。LEC可以表示以下各个组件 编造情节记忆的内容。然而，这个角色并没有得到那么多的试验性 调查和验证与MEC的作用相比较。因为LEC在 年龄相关性记忆障碍的早期阶段，包括阿尔茨海默病，了解这一点是非常必要的 详细地讲，LEC中表示的信息类型以及作为其基础的神经编码机制 申述。最近的研究为LEC神经表征提供了两个基本的见解：(1) LEC编码一个时间背景信号，允许大脑代表和区分事件的记忆 发生在不同的时间点；以及(2)LEC代表外部物品相对于 以自我为中心的参照系中的观察者。后一种观点与LEC提供的概念一致 海马体，具有关于一集内容的第一人称信息，经历和记忆 从自我中心的角度来看。我们假设，标志着早期年龄阶段的助记缺陷- 相关的认知功能下降和阿尔茨海默氏症可能是由于正常的时间编码和 LEC输入到海马区的以自我为中心的编码。为了检验这一假设，我们将确定 青年大鼠、无记忆障碍的老年大鼠和有记忆障碍的老年大鼠之间存在差异 LEC神经元这些特性的损害。这些实验承诺提供关键的新数据和 对内侧颞叶功能障碍如何导致轻度到严重的记忆损害的洞察 范围从老年人的轻微不便到严重的丧失工作能力。

The hippocampus and medial temporal lobe are crucial components of the brain’s declarative memory system. Extensive damage to these structures results in devastating and permanent loss of the ability to form new, conscious memories of facts and personal experience. Aging is strongly associated with loss or change of memory functions, in both normal aging and in neuropathological conditions. The lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) provide the large majority of medial temporal lobe input to the hippocampus. The MEC appears to provide the hippocampus with a signal about the spatial location of an organism. This signal is thought to act as a framework that allows the hippocampus to bind together the individual components of an experience that occur at a moment in space and time. This framework allows the hippocampus to form a coherent representation that is stored and later retrieved as an episodic memory. The role of the LEC in this system has been less explored. The LEC may represent the individual components that make up the content of an episodic memory. However, this role has not received as much experimental investigation and validation compared to the role of MEC. Because the LEC is particularly vulnerable in the early stages of age-related memory impairment, including Alzheimer’s Disease, it is imperative to understand in detail the types of information represented in LEC and the neural coding mechanisms that underlie these representations. Recent studies have provided two fundamental insights into LEC neural representations: (1) LEC encodes a temporal context signal that allows the brain to represent and distinguish memories of events that occur at different points in time; and (2) LEC represents the bearing of external items relative to the observer in an egocentric frame of reference. The latter insight is consistent with the notion that LEC provides the hippocampus with first-person information about the content of an episode, experienced and remembered from an egocentric perspective. We hypothesize that the mnemonic deficits that mark early stages of age- related cognitive decline and Alzheimer’s Dementia may result from the loss of normal temporal coding and egocentric coding of the LEC inputs to the hippocampus. To test this hypothesis, we will determine whether there are differences among young rats, aged rats without memory impairment, and aged rats with memory impairment in these properties of LEC neurons. These experiments promise to provide crucial new data and insights into how medial temporal lobe dysfunction produces the mild to severe memory impairments that can range from minor inconvenience to devastating incapacity in aged individuals.