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延长，伴随着正常衰老而出现的情景记忆下降是公众健康日益关注的问题。海马体是长期情景记忆和语义记忆的关键结构，从内嗅觉皮质(EC)的浅层接受主要输入。在海马体内进行信息处理后，EC的深层依次接受输出。海马体本身的改变可能是正常衰老时出现的情景记忆下降的原因，但也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)似乎处理有关自我运动和位置的信息，而外侧内嗅皮层(LEC)似乎处理有关外部环境中物体的信息。本申请建议研究老化对EC在其表层和深层对关于两个视觉不同环境的信息进行编码的能力的影响，以及确定与MEC的路径集成器功能相比，老化是否对LEC的对象表示具有不同的影响。幼鼠(6月龄)和老年鼠(24月龄)将在同一房间的固定轨道上跑步两次。在会话之间，轨迹上的对象将完全改变。第一次会议激活的神经元将通过其细胞核中即刻早期基因(LEG)Homeria mRNA的表达而可视化，而第二次会议激活的神经元将表达腿部Arc。我们将使用原位杂交技术对mRNA进行可视化，使用共聚焦显微镜对组织进行成像，并使用我们的半自动叉尾鱼软件来量化每一次(或两次)行为过程中激活的神经元，这是基于细胞核中存在哪条腿的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一阶段激活神经元的相对比例，或者影响经验激活的神经元总数。对EC表层和深层的分析将使我们能够评估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与年龄相关的变化。随着平均寿命的持续增长，详细了解衰老对认知的影响是至关重要的。这项应用旨在研究大脑结构的完整性，这些结构在正常衰老过程中对记忆功能至关重要。这一结果将有助于研究人员通过表征这些结构的功能在老年时是如何改变的，从而将衰老对记忆功能的影响降至最低。

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.