NMDA Receptor-Dependent Dynamics of Hippocampal Place Cell Ensembles

The hippocampus is a key brain area to encoding and storing memories. Hippocampal place cells encode the position of an animal in space by firing when the subject is at a specific location in the environment. Therefore, place cells are considered essential to spatial memory and navigation. It has recently been revealed that place-cell activity is not constant even in a familiar environment, but changes dynamically over time. However, the mechanism behind these changes in activity is not yet fully understood. In this study, the activity of hippocampal CA1 neurons of male mice was tracked during repeated performances of a spatial task in a virtual reality environment. By comparing place-cell ensemble representations among repeated performance of the task, the overlap rate of the active place-cell population was found to be time dependent but independent of the number of tasks within a fixed time. These findings suggest that place codes change automatically and at a constant speed. Furthermore, the dynamics of place-cell activity were found to be suppressed by an NMDA receptor antagonist. In summary, the spontaneously dynamic nature of place-cell activity is at least in part regulated by NMDA receptors, and the dynamics may encode temporal information of episodes.SIGNIFICANCE STATEMENT Place-cell activity in the hippocampal CA1 area is not stable even in a familiar environment, but changes dynamically over time. However, the mechanism behind these changes is unknown. Using in vivo calcium imaging, activity of CA1 neurons were tracked during multiple sessions with variable intervals. The overlap rate of the active place-cell population was constant regardless of the number of tasks within a fixed time. Furthermore, the dynamics were suppressed by an NMDA receptor antagonist. This NMDA receptor-dependent, continuous change in the place-cell activity may encode temporal information of episodes.