Long-term dynamics of CA1 hippocampal neural ensemble representations of space

Hippocampal place cells are considered basic substrates of spatial memory, but the degree to which their ensemble representations of space are stable over long time periods has remained unmeasured. By using an integrated, miniature microscope, and micro-endoscope probes, we performed Ca²⁺-imaging in behaving mice as they repeatedly explored a familiar environment. This approach allowed us to track the place fields of thousands of CA1 hippocampal neurons over weeks. Spatial coding was highly dynamic, for on each day the neural representation of this environment involved a unique subset of neurons. A minority of the cells (~15–25%) overlapped between any two of these subsets and retained the same place fields.  Although this overlap was also dynamic it sufficed to preserve a stable and accurate ensemble representation of space across weeks. These findings raise several important questions: What are the biological mechanisms that drive the turnover in the place cell membership of each day’s coding ensemble? What is the functional relevance of these dynamics to hippocampal memory? Overall, this work reveals a dynamic time-dependent facet of the hippocampal representation of space, and introduces a novel approach for investigating, in a behaving animal, how coding in large neuronal populations changes over long periods of time and as function of experience.