Hippocampal Network Profiles of Memory Aging

描述（由申请人提供）：我们理解记忆老化的主要障碍之一是缺乏有效的工具来解决基本问题，例如：什么是记忆痕迹？在衰老过程中，网络水平的动态和记忆编码模式的主要变化是什么？我们如何才能识别出在老年大脑中产生上级记忆功能的网络特征？在这个应用中，我们建议应用大规模合奏记录方法来识别，可视化，并在整个记忆过程的所有主要阶段，即在年轻的成年人和老年人的大脑中的CA1区域的记忆痕迹的特征，收购，巩固和检索。在我们的应用程序中，我们假设，独特的激活和再激活模式的CA 1细胞组件形成的网络水平的基础上预测的记忆测试中的行为表现。我们将通过研究以下四个具体问题来检验这一关键假设：1）在记忆获得、巩固和提取过程中，CA1活动的总体模式是什么？2)与行为记忆表现相关的基本网络水平特征是什么？3)衰老过程是如何影响这些特征的？4)NR2B在调节衰老过程中增强记忆的网络水平特征中的作用是什么？可以想象，识别和可视化CA1记忆痕迹应该使我们能够操纵和发现老年大脑记忆衰退的神经过程。这种新的能力和知识应该导致新的策略，为潜在的治疗干预记忆老化。 公共卫生相关性：随着年龄的增长，人和动物都表现出认知功能的退化。注意力和记忆力逐渐下降的神经基础知之甚少。基于我们最近成功地应用大规模体内记录技术和计算算法来监测和分析自由行为小鼠CA1区域中数百个单个神经元的活动模式，我们建议识别和表征年轻和老年动物的网络级记忆痕迹。此外，我们将研究年轻和老年NR2B转基因小鼠增强记忆功能的神经网络基础。我们将比较野生型老年小鼠和转基因老年小鼠之间的相似性和差异。可以想象，网络级记忆痕迹的识别和生物物理学描述应该为记忆是什么以及记忆如何随着年龄的增长而改变的问题提供关键的见解。

DESCRIPTION (provided by applicant): One of the major obstacles in our understanding of memory ageing is lack of an effective tool to address the fundamental questions such as: what are memory traces? What are the major alterations in the network-level dynamics and memory-encoding patterns during aging? How can we identify network characteristics that give rise to superior memory function in the aged brain? In this application, we propose to apply large-scale ensemble recording method to identify, visualize, and characterize memory traces in CA1 region throughout all major stage of the memory process, namely, acquisition, consolidation, and retrieval in both young adult and aging brains. In our application, we hypothesize that unique activation and reactivation patterns by CA1 cell assemblies form the network-level basis for predicting behavioral performances in memory tests. We will test this key hypothesis by examining four specific questions: 1) what are the ensemble patterns of CA1 activity during memory acquisition, consolidation, and retrieval? 2) What are the fundamental network-level characteristics that are correlated with behavioral memory performances? 3) How does the aging process affect those characteristics? 4) What is the role of the NR2B in the regulation of network-level features underling the enhanced memory during ageing? It is conceivable that identification and visualization of CA1 memory traces should enable us to manipulate and discover the neural processes underlying memory decline in the old brain. Such a new capacity and knowledge should lead to new strategies for potential therapeutic interventions for memory ageing. PUBLIC HEALTH RELEVANCE: Both people and animals exhibit deterioration of cognitive function as they age. The neural bases for the gradual decline in attention and memory are poorly understood. Based on our recent success in applying large-scale in vivo recording techniques and computational algorithms for monitoring and analyzing activity patterns of over hundreds of individual neurons in the CA1 region of freely behaving mice, we propose to identify and characterize network-level memory traces in both young and old animals. Moreover, we will investigate the neural network basis underlying enhanced memory function in young and aged NR2B transgenic mice. We will compare the similarity and differences between wild-type aged mice and transgenic aged mice. It is conceivable that the identification and biophysical description of network-level memory traces should provide crucial insights into the question of what memory is, and how memory is altered by ageing.