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加，伴随正常衰老的情景记忆下降越来越受到公众健康的关注。海马是长时情景记忆和语义记忆的关键结构，主要接受来自内嗅皮层（EC）浅层的输入。EC的深层依次接收海马内信息处理后的输出。海马体本身的改变可能是伴随正常衰老发生的情景记忆下降的基础，然而，上游或下游结构的缺陷也可能导致已知的行为缺陷。内侧内嗅皮层（MEC）似乎处理有关自我运动和位置的信息，而外侧内嗅皮层（LEC）处理有关外部环境中物体的信息。该应用程序提出了调查老化的影响的能力的EC编码信息的两个视觉上不同的环境在其表层和深层，以及确定老化是否有差异的影响相比，路径积分器功能的MEC的LEC的对象表示。年轻（6个月）和老年（24个月）大鼠将在同一房间的固定轨道上运行两个阶段。在会话之间，轨道上的对象将完全改变。由第一阶段激活的神经元将通过其核中的立即早期基因（IEG）Homeria mRNA的表达而可视化，而由第二阶段激活的神经元将表达IEG Arc。将采用原位杂交来可视化mRNA，共聚焦显微镜将用于对组织成像，并且我们的半自动化catFISH软件将用于定量由每个（或两个）行为会话激活的神经元，所述行为会话基于哪个IEG mRNA存在于核内。将使用标准多变量统计分析结果，以确定老化是否影响每次会话期间激活神经元的相对比例或经验激活的神经元总数。对EC的表层和深层的分析将允许在向海马提供直接输入的细胞中以及在接收直接海马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长的趋势，详细了解衰老对认知的影响至关重要。本申请旨在研究正常衰老期间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如何改变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.