Abstract
Efficient navigation through space encompasses the ability to maintain a representation of self-location relative to the external environment in real behavioral time. Beyond the here and now, recalling a past experience or imagining a future scenario can be rather rapid, but experienced as if it were occurring in real time. Interestingly, damage to the hippocampus or its interactions with the prefrontal cortex impairs navigational decisions, memory retrieval, and future planning. How could the hippocampal-prefrontal system flexibly support these distinct timescale functions? To investigate the underlying physiological mechanisms, we continuously tracked the same hippocampal and prefrontal ensembles in rats throughout learning of a spatial alternation task. We found flexible expression of neuronal sequences at multiple timescales in both regions, including slow behavioral-timescale sequences (~seconds), as well as two types of fast sequences (~100-200 ms) as theta sequences during online periods and replay sequences during offline periods. The focus of my dissertation was to characterize and assess the function roles of these sequences, and to consider how these multiple-timescale neural codes may function as neuronal substrates to link memory to navigational decisions.
This dissertation first examines hippocampal-prefrontal replay in awake versus sleep states, and further discusses our findings in the context of earlier studies towards a framework of how sleep and awake replay may work together to support learning and memory. Second, it investigates the learning dynamics of hippocampal-prefrontal replay, and how such dynamics contribute to different stages of learning to support our ability of retrospective evaluation and prospective planning. Third, it interrogates the functional roles of theta sequences in both the hippocampus and prefrontal cortex, and considers the idea of how replay and theta sequences may contribute to complementary parts of a coordinated mechanism for learning and memory. Finally, it provides a synthesis of these observations, and suggests that these multiple-timescale neural codes in the hippocampal-prefrontal system contribute to flexible use of memories for future planning during navigational decisions.