Examining the neural basis of long-term memories and its dependence on connections between entorhinal and prefrontal cortices

在哺乳动物的大脑中，形成对日常事件的记忆需要位于内侧颞叶的海马体。最初，海马体对于检索这些记忆也很关键；然而，这种对海马体的依赖是有时间限制的。最近的一项研究利用动物的联想学习任务作为模型系统来研究人类事件记忆，发现虽然习得记忆关联的表达最初需要功能性海马，但记忆依赖行为后来依赖于内侧前额叶皮层。一项相关研究表明，内侧前额叶皮层的神经元随着该区域成为记忆所必需的区域，逐渐发展出选择性获得性记忆的活动模式。这些结果表明，随着时间的推移，记忆逐渐嵌入到新皮层网络中，并揭示内侧前额叶皮层是该网络中的关键节点。然而，他们留下了一个悬而未决的问题，即内侧前额叶皮层是如何与大脑中与长期记忆有关的其他区域相互作用的，以及这种相互作用是如何介导长期记忆的。在长期记忆所必需的几个大脑区域中，内侧颞叶的损伤会导致记忆功能最严重的衰退。这一建议涉及一系列研究，旨在研究内侧前额叶皮层如何与内侧颞叶相互作用，以表征、存储和表达长期记忆。如果成功，这项研究将进一步表征内侧前额叶皮层在长期记忆中的作用，并将其与文献记载的内侧颞叶功能联系起来。因此，这项研究将大大提高我们对大脑如何长时间代表和存储关于日常事件的信息的理解，并为研究当人们变老或患有精神疾病时大脑如何恶化提供参考。

In the mammalian brain, forming memories for daily events requires the hippocampus, located in the medial temporal lobe. Initially, the hippocampus is also critical for retrieving these memories; however, this dependence on the hippocampus is time-limited. Using animals' associative learning task as a model system to study human event memory, a recent study found that while the expression of the learned memory association initially requires a functional hippocampus, memory-dependent behavior later comes to depend on the medial prefrontal cortex. A related study demonstrated that neurons in the medial prefrontal cortex gradually develop activity patterns selective for the acquired memory with the same time course as the region becomes necessary for memory. These results suggest that as time passes memories are gradually embedded into the network of neocortex, and reveal that the medial prefrontal cortex is a critical node in that network. They leave an open question, however, of how the medial prefrontal cortex interacts with other areas of the brain that are implicated for long-term memory, and how such an interaction mediates long-term memories. Among several brain areas that are necessary for long-term memory, damage to the medial temporal lobe produces the most profound failure in memory function. This proposal involves a series of studies that are designed to examine how the medial prefrontal cortex interacts with the medial temporal lobe to represent, store and express long-term memories. If successful, this study will further characterize the newly proposed role of the medial prefrontal cortex in long-term memory, and will connect it with the well-documented functions of medial temporal lobe. As such, this study will significantly improve our understandings of how the brain represents and stores the information about daily events for a long period of time, and provide a reference to investigate how it deteriorates when people age or suffer mental illness.