Age effects on grid cell and scene recognition systems of entorhinal cortex

描述（由申请人提供）：随着平均寿命的持续增长，伴随正常衰老的情景记忆衰退日益成为公众健康关注的问题。海马体是长期情景记忆和语义记忆的关键结构，主要接收来自内嗅皮层浅层的输入。EC的深层依次接收海马体内信息处理后的输出。海马体本身的改变可能是随着正常衰老而发生的情景记忆衰退的基础，然而，也有可能是上游或下游结构的缺陷也导致了已知的行为缺陷。内侧内嗅皮层（MEC）处理自我运动和位置信息，而外侧内嗅皮层（LEC）处理外部环境中物体的信息。该应用程序旨在研究老化对EC在其表层和深层两个视觉上截然不同的环境中编码信息的能力的影响，以及确定与MEC的路径积分器函数相比，老化对LEC的对象表示是否有不同的影响。幼鼠（6个月大）和大鼠（24个月大）将在同一个房间的固定轨道上跑两个阶段。在会话之间，赛道上的物体将完全改变。第一阶段激活的神经元将通过其细胞核中直接早期基因（lEG） Homeria mRNA的表达来可视化，而第二阶段激活的神经元将表达lEG Arc。原位杂交将用于可视化mRNA，共聚焦显微镜将用于组织成像，我们的半自动catFISH软件将用于量化每一个（或两种）行为会话激活的神经元，基于细胞核中存在的lEG mRNA。结果将使用标准的多变量统计进行分析，以确定衰老是否会影响每次会话中激活神经元的相对比例或被经验激活的神经元总数。对EC的浅层和深层的分析将允许在向海马体提供直接输入的细胞以及接受海马体直接输出的细胞中评估与年龄相关的变化。随着平均寿命持续增加的趋势，详细了解衰老对认知的影响至关重要。该应用程序旨在研究在正常衰老过程中对记忆功能至关重要的大脑结构的完整性。研究结果将帮助研究人员通过描述这些结构的功能在老年时是如何改变的，来最大限度地减少衰老对记忆功能的影响。

DESCRIPTION (provided by applicant): Declines in episodic memory that accompany normal aging are a growing concern for public health as the average lifespan continues to increase. The hippocampus is a critical structure for long-term episodic and semantic memories and receives major input from the superficial layers of entorhinal cortex (EC). The deep layers of EC in turn receives output following information processing within the hippocampus. Alterations within the hippocampus itself may underlie declines in episodic memory that occur with normal aging, however it is also possible that defects in upstream or downstream structures also contribute to the known behavioral deficits. The medial entorhinal cortex (MEC) appears to process information about self-motion and position while the lateral entorhinal cortex (LEC) processes information about objects in the external environment. This application proposes to investigate the effects of aging on the ability of the EC to encode information about two visually distinct environments in both its superficial and deep layers, as well as to determine if aging has differential effects on the object representations of the LEC compared with the path integrator function of the MEC. Young (6 months) and old (24 months) rats will run on a fixed track in the same room for two sessions. Between sessions the objects on the track will be completely changed. Neurons activated by the first session will be visualized by the expression of the immediate early gene (lEG) Homeria mRNA in their nucleus, while neurons activated by the second session will express the lEG Arc. In situ hybridization will be employed to visualize mRNA, confocal microscopy will be used to image the tissue, and our semi-automated catFISH software will be used to quantify neurons activated by each (or both) behavioral sessions based on which lEG mRNA is present within the nucleus. The results will be analyzed using standard multivariate statistics to determine if aging affects either the relative proportions of activated neurons during each session or the total numbers of neurons activated by experience. The analysis of both the superficial and deep layers of EC will allow age-related changes to be assessed in cells that provide direct input to the hippocampus as well as in cells that receive direct hippocampal output. Detailed understanding of the effects of aging on cognition is of paramount importance as the trend of increasing average lifespan continues. This application proposes to investigate the integrity of brain structures that are critical for memory function during normal aging. The results will assist researchers to minimize the effects of aging on memory function by characterizing how the function of these structures is altered in old age.