Neural Mechanisms of Spatial Memory: Dissociating the Encoding and Retrieval of Hippocampal Replay

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Date
2014-08-19
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Johns Hopkins University
Abstract
How memories are encoded and stored is a fundamental question in neuroscience. The hippocampus, a well-established brain region for memory and learning, plays a critical role in the initial encoding and consolidation of spatial memory. The discovery of place cells, hippocampal neurons that increase their firing rate when an animal is in a particular region of an environment, was the first demonstration that space could be encoded in the firing pattern of the hippocampus. The place field, a place cell’s preferred firing region, only encodes spatial information about the animal’s current location. However, spatial navigation and memory involve a sequence of locations. By analyzing hippocampal spatial activity at the network level, recurring sequences matching the rat’s previous spatial experience were found in both sleep and awake behavior. Replay, the sequential reactivation of a recent trajectory played in reverse, occurs during memory retrieval and is important for the establishment of memory traces. Thus, it is of considerable interest to understand how and when spatial replay occurs. This dissertation examines the hypothesis that hippocampal replay constitutes a neuronal model system for memory formation dependent upon both experience and NMDAR function. We employed ultrahigh density recording methods to monitor hundreds of place cells simultaneously during novel experience, enabling measurement of spatially coordinated activity on timescale of tens of milliseconds, and measurement of the depiction of moving trajectories on a 100ms timescale. We demonstrate that hippocampal replay is dependent on molecular mechanisms associated with learning-related plasticity and are able to dissociate the encoding and retrieval phases of memory processing during spatial navigation.
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Keywords
hippocampus, replay, memory
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