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，网络级动态和记忆编码模式的主要变化是什么？我们如何识别老年大脑中产生卓越记忆功能的网络特征？在这个应用中，我们建议应用大规模集合记录方法来识别、可视化和表征CA1区域在记忆过程的所有主要阶段，即在年轻人和衰老的大脑中获取、巩固和检索的记忆痕迹。在我们的应用中，我们假设CA1细胞集合的独特激活和再激活模式构成了预测记忆测试行为表现的网络级基础。我们将通过检查四个具体问题来检验这一关键假设：1)在记忆获取、巩固和检索过程中CA1活动的整体模式是什么？2)与行为记忆表现相关的基本网络级特征是什么？3)老化过程如何影响这些特征？4) NR2B在衰老过程中对网络水平特征的调控作用是什么？可以想象，CA1记忆痕迹的识别和可视化应该使我们能够操纵和发现老年大脑中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。

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.