Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, INSERM, F-33000 Bordeaux, France.
Université de Bordeaux, F-33000 Bordeaux, France.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10262-10267. doi: 10.1073/pnas.1619657114. Epub 2017 Sep 5.
Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are compromised in age-related memory loss remain hypothetical. We here identify a causal link between these two features of declarative memory: Temporal binding is a necessary condition for the relational organization of discontiguous events. We demonstrate that the formation of a relational memory is limited by the capability of temporal binding, which depends on dorsal (d)CA1 activity over time intervals and diminishes in aging. Conversely, relational representation is successful even in aged individuals when the demand on temporal binding is minimized, showing that relational/declarative memory per se is not impaired in aging. Thus, bridging temporal intervals by dCA1 activity is a critical foundation of relational representation, and a deterioration of this mechanism is responsible for the age-associated memory impairment.
时间绑定，即能够将记忆中不连续刺激关联起来的过程，以及关系组织，即能够使陈述性记忆具有灵活性的过程，都依赖于海马体并且随着年龄的增长而衰退。然而，这两个过程在支持陈述性记忆形成方面是如何相关的，以及它们在与年龄相关的记忆丧失中是如何受到影响的，仍然是假设性的。我们在这里确定了陈述性记忆的这两个特征之间的因果关系：时间绑定是不连续事件的关系组织的必要条件。我们证明，关系记忆的形成受到时间绑定能力的限制，而时间绑定能力取决于背侧（d）CA1 在时间间隔内的活动，并且随着年龄的增长而减弱。相反，即使在老年人中，当对时间绑定的需求最小化时，关系表示也是成功的，这表明关系/陈述性记忆本身在衰老中并没有受损。因此，dCA1 活动跨越时间间隔是关系表示的关键基础，而这种机制的恶化是与年龄相关的记忆损伤的原因。
