A Circuit-Level Model of Hippocampal, Entorhinal and Prefrontal Dynamics Underlying Rodent Maze Navigational Learning.

摘要

Interactions between the hippocampus, parahippocampal regions and the prefrontal cortex are thought to underlie the formation, consolidation, and retrieval of short term memories and play an important role in the learning processes. To date, only conceptual models have been offered to explain the potential interactions among these regions, but their connectivity and synaptic regulation remain unknown. To better understand sequential learning and decision making during spatial navigation, a large-scale biological model was needed to further guide experimental studies. The results of a putative entorhinal grid cell and hippocampal place cell circuit-level model was reported, incorporating Hebbian learning, ion channels, and asynchronous background activity in the context of recent in vivo findings showing specific intracellular-extracellular precession disparities and place field destabilization by entorhinal lesioning. A more complex model was then proposed by adding another hippocampal formation structure, the subiculum, in a complete recurrent loop with the prefrontal cortex. The model replicated some of the dynamics of the mammalian hippocampal-frontal loop microcircuitry, including phase synchrony of prefrontal cells to hippocampal theta oscillations. It also demonstrated short-term augmentation of navigational sequences, decision making, and learning reinforcement. To demonstrate the computational model's functionality, a graphic environment with a navigating virtual mouse was created and could be used for further real-time simulations. Finally, to refute or support the proposed mechanisms of hippocampal-entorhinal dynamics, future experimental studies were proposed to test the types of extrinsic connectivity between the entorhinal cortex and the hippocampus and the intrinsic connectivity within the subiculum.