Extended Data Fig. 10: High and low activity principal cells make distinct contributions to network co-firing motifs.

a, Cumming estimation plots showing CPP task-related changes in topological clustering (top), geodesic path length (middle) and single-neuron cumulative co-firing strength (bottom) of co-firing graphs (with respect to exposure) for low and high activity cells. Black-dots, median; black-ticks, 95% confidence interval; filled-curve: sampling-error distribution. b, Top, schematic showing the location of the containers for the sucrose and water drops in an example CPP enclosure. Bottom, distribution of firing rate changes (scores) between the +Suc and pre-test sessions for low and high activity cells (low activity cells: p=2.68x10^-5, t=4.279, df=251; high activity cells: p=0.25, t=1.160, df=271; 1-sample t-tests against 0 mean). For every cell that fired at least 100 spikes in either session, a score is obtained by taking the difference between its mean firing rate at the containers during +Suc and pre-test sessions, dividing by the sum. c, The change in firing rate at the containers from pre-test to +Suc. session correlated with the change in co-firing strength from exposure to re-exposure for the low (regression line y=0.21x-0.11; p=0.018, Wald test) but not the high (regression line y=0.12x-0.23; p=0.51, Wald test) activity cells. Together with the topological deviations that feature the low activity cell co-firing graphs (a), this result supports the idea that during the mnemonic update of a newly encountered place with reward experience, a change in the firing activity of low activity cells allows a cross-talk between the new CPP memory and the prior representation of the familiar enclosure, as reported along PC3 (Fig. 3d). d, Contribution of low and high activity cells to network co-firing motifs, as measured by the proximity between the high (right) and low (left) activity sub-networks to the whole network (that is, containing the full distribution of all recorded neurons) in the topological distance space across the six CPP task events (w.r.t. low activity cells in exposure). Black-dot, median or mean as indicated; black-ticks, 99% confidence interval; filled-curve: sampling-error distribution. e, For low and high activity cells, firing rate changes during sharp-wave/ripples (SWRs) detected in periods of immobility (speed<2cm/sec) of exposure and re-exposure sessions. For every cell, the change in SWR firing is measured as the difference between its mean firing rate during SWRs in the exposure and re-exposure sessions divided by the subpopulation’s average firing rate during SWRs of exposure. f, Change in co-firing during SWRs between exposure and re-exposure for low-low, low-high and high-high activity cell pairs. SWR co-firing computed during SWRs detected in periods of immobility (speed<2cm/sec) of a given exploration session in the familiar enclosure. The change in co-firing between re-exposure and exposure was then divided by the average subpopulation’s co-firing. Note the increased SWR co-firing between low-low and low-high activity cells during the re-exposure session following CPP learning.