Hippocampal ensemble dynamics timestamp events in long-term memory.

TL;DR: Time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments suggests that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance.

Abstract: The ability to recall the timing of events is an important feature of long-term memory. Episodic memory, the mental account of “what” happened, “where” and “when”, depends on a region of a brain called the hippocampus. Certain neurons in the hippocampus, called place-cells, are known to capture information about the locations an animal has visited so that a specific pattern of place cell activity marks each location an animal visits. However, it is not clear how the brain can mark the relationship between the timing of different events. Some studies have documented gradual changes in the activity patterns of the place cells over time, which could help mark time. If these changes are specific to a particular environment then they would not allow animals to associate in memory events that occurred close in time (for instance, in the same day) if these events occurred in different environments. To do that, a certain component of the changes in the activity patterns would have to be independent of any specific environment or context in which events occur. Now, Rubin, Geva et al. have captured time-lapse images of the activity of thousands of hippocampal cells in mice as they explored two different environments on repeated occasions over a two-week period. The environments had different shapes, textures, visual cues, and odors. The mice were allowed to explore each environment daily for more than a week prior to the time-lapse filming so that they would be very familiar with the two environments. During the filming portion of the experiments, the mice visited one environment in the morning, and then the other in the afternoon. The analysis of the images revealed what appeared to be unique patterns of cell activity for specific days, which gradually changed over the course of the experiment. The patterns persisted even when the animals switched to a new environment during the same day, but were different for visits to the same environment on different days. Next, Rubin, Geva et al. used the patterns of activity collected from the mice while they were in one environment to create a timeline of events. From this timeline, it was possible to accurately deduce which day each visit to the other environment occurred based on the patterns of hippocampal cell activity alone. One challenge that stems from this work is to understand the biological mechanisms that drive the patterns in neuronal activity over timescales that are relevant for long-term memory.