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

项目 1-基于行为特征老年大鼠的外侧和内侧内嗅信息处理流的神经编码

• 批准号: 10171060
• 负责人: JAMES J KNIERIM
• 金额: $ 44.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10171060
• 关键词: Age-associated memory impairment; Aging; Alzheimer' s Disease; Behavioral; Binding; Brain; Brain region; Cells; Code; Cognition; Cognitive; Conscious; Data; Episodic memory; Event; Functional disorder; Head; Hippocampus (Brain); Hour; Individual; Investigation; Lateral; Life; Location; Machine Learning; Medial; Memory; Memory impairment; Minor; Neurons; Organism; Paper; Persons; Population; Prevalence; Property; Rattus; Research Personnel; Role; Signal Transduction; Smell Perception; Speed; Stream; Structure; System; Techniques; Temporal Lobe; Testing; Time; Validation; Vision; age difference; age related; aged; base; cell cortex; entorhinal cortex; experience; experimental study; information processing; insight; neocortical; normal aging; relating to nervous system; remote location; sound

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.

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的和永久性的丧失形成新的， 对事实和个人经历的有意识记忆。衰老与失去或改变 记忆功能，在正常老化和神经病理条件下。外侧内嗅皮层 (LEC)和内侧内嗅皮层（MEC）提供了大部分的内侧颞叶输入到 海马体。MEC似乎为海马提供了一个关于神经元空间位置的信号。 有机体这种信号被认为是一种框架，允许海马体将神经元结合在一起。 在空间和时间的某个时刻发生的经验的各个组成部分。该框架允许 海马体形成连贯的表征，该表征被存储并随后作为情景记忆被检索。的 LEC在该系统中的作用较少被探索。LEC可以表示 构成情景记忆的内容。然而，这一作用并没有得到太多的实验 与MEC的作用相比，调查和验证。因为LEC在地球上特别脆弱， 与年龄有关的记忆障碍的早期阶段，包括阿尔茨海默病，必须了解 详细介绍了LEC中代表的信息类型以及这些信息的神经编码机制 表示。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，使大脑能够代表和区分事件的记忆 （2）LEC表示外部项目相对于 在一个自我中心的参照系中观察。后一种观点与LEC提供的概念一致， 海马体与第一人称信息的内容，一集，经验和记忆 从自我中心的角度来看。我们假设记忆力的缺陷标志着年龄的早期阶段- 相关的认知下降和阿尔茨海默氏痴呆症可能是由于正常时间编码的丧失， LEC输入到海马的自我中心编码。为了验证这一假设，我们将确定 青年大鼠、无记忆障碍老年大鼠和有记忆的老年大鼠之间存在差异 LEC神经元的这些特性的损害。这些实验有望提供关键的新数据， 了解内侧颞叶功能障碍如何产生轻度至严重的记忆障碍， 范围从轻微的不便到老年人的毁灭性丧失能力。