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

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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.