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Navigating the environment requires the integration of distance, direction, and place information, which critically depends on hippocampal place and entorhinal grid cells. Studies in rodents have shown, however, that substantial changes in the environment’s surroundings can trigger a change in the set of active place cells, accompanied by a rotation of the grid cell firing pattern (Fyhn et al., 2007) - a phenomenon commonly referred to as global remapping. In the present study, we investigated whether human grid and place cells show a similar remapping behavior in response to environmental changes and whether different episodes in the same environment might cause remapping as well. In two experiments, participants underwent 3T fMRI scanning while they navigated a virtual environment, comprising two different rooms in which objects were placed in random locations. Participants explored the first room and learned these object-location conjunctions (learning-phase), after which the objects disappeared and participants were asked to navigate repeatedly to the different object locations (test-phase). This procedure (i.e. a learning- and test-phase within a room) was repeated several times, separated by different events, such as leaving and re-entering the same room, or moving to the second, different room. Indicators of grid cell firing were derived from the BOLD activation while participants moved within the virtual environment, whereas indicators of place cell firing were derived from the activation patterns while participants were standing at particular object locations. We compared these indicators between the different rooms and events to investigate how these manipulations influence remapping. Overall, our findings demonstrate entorhinal grid cell and hippocampal place cell remapping in humans. Furthermore, our results suggest that beside environmental changes, also other events (e.g., re-entering the same environment) might evoke remapping. We conclude that, in humans, remapping is not only environment-based but also event-based and might serve as a neural mechanism to create distinct memory traces for episodic memory formation.
