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: 8935170
• 负责人: JAMES J KNIERIM
• 金额: $ 36.02万
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8935170
• 关键词: Address; Affect; Aging; Animals; Antiepileptic Agents; Behavior; Cell Aging; Cells; Characteristics; Chemosensitization; Cognition; Conflict (Psychology); Consensus; Cues; Elderly; Environment; Episodic memory; Event; Exploratory Behavior; Fire - disasters; Functional disorder; Geometry; Head; Hippocampus (Brain); Impaired cognition; Impairment; Incidence; Individual; Lateral; Learning; Levetiracetam; Link; Location; Maintenance; Medial; Memory; Memory Loss; Memory impairment; Motion; Neuronal Plasticity; Pattern; Physiological; Play; Process; Property; Rattus; Relative (related person); Role; Rotation; Scanning; Sensory; Signal Transduction; Site; Specificity; Stream; Structure; System; Temporal Lobe; Testing; Work; age related; aged; aging hippocampus; base; cell age; entorhinal cortex; experience; information gathering; information processing; juvenile animal; neurophysiology; normal aging; novel; pathological aging; place fields; relating to nervous system; research study; response; spatiotemporal

The hippocampus and medial temporal lobe structures play critical roles in the formation and maintenance of declarative memories. A consensus is emerging that the hippocampus receives a self-motion-based, spatial signal from the medial entorhinal cortex (MEC) and an external sensory signal about objects and items in the world from the lateral entorhinal cortex (LEC). It combines these inputs to create conjunctive representations of discrete experiences within their spatiotemporal contexts. Because memory loss is one of the hallmark characteristics of both normal and pathological aging, a key challenge is to understand the physiological changes that occur in the hippocampus with aging. Recent results suggest that the LEC is particularly susceptible to age-related dysfunction. Moreover, treatment with the antiepileptic drug, levetiracetam, can ameliorate some of the physiological and cognitive impairments associated with aging. This project proposes a number of experiments to test specific hypotheses about how LEC and MEC inputs affect hippocampal function with aging. Place cells of aged rats with impaired memory show a reduced control by local sensory cues (associated with neural representations of the LEC), whereas they continue to be controlled by global spatial cues (associated with representations of the MEC). Place cells of the CA3 region will be recorded from young rats and from aged rats (with and without memory impairments) in the following experiments. (a) Local and global spatial reference frames will be placed in conflict. It is hypothesized that aged impaired rats will show an abnormal lack of control by the local reference frame, and that this abnormal condition will be ameliorated by treatment with levetiracetam. (b) The geometry and location of a recording chamber will be altered. It is hypothesized that aged impaired rats will show an abnormal stability of their place fields when only the geometry is altered (due to a hypothesized loss of LEC input) but will show normal place field changes when the location is altered (due to a hypothesized normal MEC input). The abnormal stability patterns will be ameliorated with levetiracetam treatment. (c) The formation of new place fields associated with an investigatory behavior known as head-scanning will be investigated It is hypothesized that aged impaired rats will show a reduction in the formation of new place fields associated with this behavior. Treatment with levetiracetam will restore this neural plasticity phenomenon. (d) Recordings from the MEC and LEC will test the hypothesis that grid cells, border/boundary cells, and nonspatial cells of aged impaired rats will be normal, compared to young and aged unimpaired rats. These experiments will provide robust tests of the general hypothesis that LEC neural processing is particularly susceptible to age-related dysfunction, and that levetiracetam treatment is a potential therapy to restore hippocampal function in aged-impaired animals.

海马体和内侧颞叶结构在形成和维持中起着关键作用。 陈述性记忆。一种共识正在出现，即海马体接受基于自我运动的空间 来自内侧内嗅皮层(MEC)的信号和关于物体和物品的外部感觉信号 来自外侧内嗅皮层(LEC)的世界。它组合这些输入以创建合取表示 在他们的时空背景下的离散经验。因为记忆力减退是 正常衰老和病理性衰老的特点，一个关键的挑战是理解生理学上的 随着年龄的增长，海马体发生的变化。最近的结果表明，LEC特别是 容易患上与年龄相关的功能障碍。此外，使用抗癫痫药物左乙拉西坦治疗可以 改善一些与衰老相关的生理和认知障碍。 这个项目提出了一些实验来检验关于LEC和MEC如何输入的特定假设 随着年龄的增长影响海马区的功能。记忆受损的老年大鼠的放置细胞显示对照组减少 通过局部感觉线索(与LEC的神经表示相关联)，而它们继续是 由全局空间线索(与MEC的表示相关联)控制。放置CA3区的单元 将从幼年大鼠和老年大鼠(有和没有记忆障碍)中记录如下 实验。(A)地方空间参照系和全球空间参照系将发生冲突。据推测， 衰老受损的大鼠会表现出局部参照系的异常缺乏控制，这种异常 使用左乙拉西坦治疗后，病情会有所改善。(B)录音的几何形状和位置 密室将被更改。据推测，衰老受损的大鼠将表现出其位置的异常稳定性 仅几何图形更改(由于LEC输入的假设丢失)但将显示正常位置时的字段 当位置改变时(由于假设的正常MEC输入)，字段也会改变。反常的稳定性 左乙拉西坦治疗将改善患者的症状。(C)与以下方面有关的新地点区的形成 一种被称为扫头的调查行为将被调查，假设老年人受损 老鼠会表现出与这一行为相关的新位置区域的形成减少。通过以下方式治疗 左乙拉西坦将恢复这种神经可塑性现象。(D)MEC和LEC的录音将测试 假设老年受损大鼠的网格细胞、边缘/边界细胞和非空间细胞将是正常的， 与年轻的和年老的未受损的大鼠相比。这些实验将提供对一般情况的稳健测试 假设LEC神经处理特别容易受到年龄相关功能障碍的影响，并且 左乙拉西坦治疗是恢复衰老动物海马区功能的一种潜在疗法。