Figure 3. Remapping of place cells is induced by avoidance learning.

(A) Top: bar graphs show distributions of intersession intervals between pre-training (pre) and post-extinction (post) session pairs included in the analysis. Bottom: diagram shows timeline for pre and post sessions. (B) Left: number of subsampled beeline trials did not differ significantly by training condition or session. Right: running speeds did not differ significantly by training condition; there was a marginal difference between pre vs. post running speeds in the barrier (but not drug-free or scopolamine shock) condition. (C) Left: total number of imaged place cells (recurring and non-recurring) did not differ significantly by training condition; there was a marginal difference between pre vs. post place cell counts in the barrier (but not drug-free or scopolamine shock) condition. Middle: percentage of all imaged cells (recurring and non-recurring) per session that were classified as place cells. Right: between-session place cell recurrence ratios did not differ by training condition. (D) Heatmap pairs show pre and post tuning curves for recurring place cells that were spatially tuned in the LR (top row) and RL (bottom row) running direction; both heatmaps in each pair are co-sorted by peak locations from the pre session. Pie charts show the proportion of recurring place cells (total number given at top) for which tuning curves were included in LR and RL heatmap pairs. (E) Kolmogorov–Smirnov tests show that distributions of place field peaks locations (LR and RL combined) were unchanged between pre and post sessions. (F) Mean population vector correlation matrices for the three training conditions. (G) Decoding accuracy index (DAI) at each position on the track for each of the three training conditions; ‘*’ indicates locations where decoding was significantly (p<0.05) less accurate for the drug-free condition than the other two conditions. (H) Analysis of place tuning stability scores (S) along the full short path are shown in the top row; results for L, C, and R track zones are shown in the bottom 3 rows, respectively. Left column: bar graphs show means and standard errors of S; Middle columns: boxplots show median and range of template-selected population vector correlation bins in each rat. Right column: templates used to select peri-diagonal correlation values for analysis from different track zones. †p<0.1; *p<0.05; **p<0.01; ***p<0.001.

Figure 3—figure supplement 1. Pre-training and post-extinction session data from individual rats.

As in Figure 3, heatmaps are shown for pre-training and post-extinction sessions, along with pre vs. post population vector correlation matrices. (A1) Rats (n = 9) from the drug-free shock condition that showed 48 hr avoidance retention. (A2) Rats (n = 2) from the drug-free shock condition that failed to show 48 hr avoidance retention. (B1) Rats (n = 7) from the scopolamine condition that failed to show 48 hr avoidance retention. (B2) Rats (n = 2) from the scopolamine shock condition that showed 48 hr avoidance retention. (C) Rats (n = 6) from the barrier training control condition.

Figure 3—figure supplement 2. Remapping in male versus female rats.

Statistical analyses shown in Figure 3 were performed to compare results from male versus female rats. 3 × 2 ANOVAs were performed with sex (M, F) and training condition (DF,SCP,BAR) as independent factors. (A) The change in the number of imaged place cells between pre and post sessions (measured as the number of post session cells over the number of pre session cells) did not differ for males versus females; hence, neither sex showed a tendency to gain or lose more place cells than the other after avoidance acquisition and extinction. (B) Place cell recurrence rates (RR) between the pre and post sessions did not differ for males versus females. (C) Males and females showed similar learning-induced remapping in the center of the short path (black bars) and similar blockade of this remapping by scopolamine (pink bars).

Figure 3—figure supplement 3. Pre-training and post-extinction results from drug-free (DF) rats that failed to retain avoidance and scopolamine (SCP) rats that successfully retained avoidance.

Panels (A–E) are similar to Figure 3B, C, D, F, and G, respectively. Here, results are shown for DF rats that failed to retain avoidance (n = 2) and SCP rats that successfully retained avoidance (n = 2) 48 hr after training. The sample size of rats was not sufficient to perform ANOVAs, so independent t-tests were performed to compare values included in each graph bar against values included in corresponding bars from Figure 3. The number of beeline trials per session was equalized between sessions in each rat, but not between training conditions; beeline trial counts were marginally lower in SCP rats that retained avoidance responses (panel A, left graph) compared to those in Figure 3 that failed to retain avoidance; this was because SCP rats that retained avoidance ran fewer beeline trials in the post-extinction session (probably because they were expressing residual fear despite reaching the avoidance extinction criterion), resulting in a smaller equalized number of trials. Of the two DF rats that failed to retain avoidance, one appeared to show remapping and the other did not (see individual rat heatmaps in Figure 3—figure supplement 1A2). Panel (E) shows that in the male DF rat that failed to retain avoidance or show remapping, place tuning stability (S) was significantly larger in the unsafe C zone and also in the safe R (but not L) zone compared with the mean from Figure 3 for DF rats that retained avoidance (**p<0.01, ***p<0.001). Of the two SCP rats that retained avoidance, one appeared to show remapping of the unsafe center zone and the other did not (see individual rat heatmaps in Figure 3—figure supplement 1B2). Panel (E) shows that in the male SCP rat that retained avoidance and showed remapping, S was significantly lower in the unsafe C zone (**p<0.01 with down arrow), consistent with remapping of the shock zone.

Figure 3—figure supplement 4. Place field shifts induced by remapping.

(A) Graphs show distributions of the distances (in units of spatial bins) by which remapping caused recurring place cells (from all rats included in the analyses of Figure 3) to shift their place fields toward (negative shift values) versus away from (positive shift values) the center of the short path where shock was delivered. In each graph, inset p-value shows the significance for a z-test comparison between zero and the mean of the distribution. The distributions did not differ significantly from zero in the drug-free, scopolamine, or barrier training conditions, indicating that place cells showed no bias for shifting toward or away from the shock or barrier location in any condition. (B) Graphs show distributions of the absolute distance (in units of spatial bins) by which remapping caused recurring place cells to shift their place fields before versus after avoidance learning. Inset p-values show results of a ranksum comparison between each distribution’s median shift value versus the medians of the distributions for the other two conditions. The median shift distance was significantly larger in the drug-free condition than in the scopolamine or barrier conditions, consistent with findings reported in the main text showing that remapping occurred preferentially in the drug-free condition (since larger shifts of place field centers are consistent with more place cell remapping). Median shift distances did not differ significantly between the scopolamine and barrier conditions, confirming that remapping was less prevalent in these two conditions than in the drug-free condition.

Figure 3—figure supplement 5. Shuffled analysis of remapping.

Results plotted in panels (A–D) were performed as described for corresponding results in Figure 3, except that prior to analysis, the deconvolved spike train from every beeline trial was circularly shifted by a random amount against position tracking data from the trial. (A) Heatmap pairs show pre and post tuning curves for recurring place cells (same population of cells as in Figure 3 which were classified as place cell based on their unshuffled trains) that were spatially tuned in the LR (top row) and RL (bottom row) running direction; both heatmaps in each pair are co-sorted by peak locations of the shuffled tuning curve from the pre session. (B) Distributions of shuffled tuning curve peak locations (LR and RL combined) are no longer concentrated preferentially at the ends of the track. (C) Mean population vector correlation matrices calculated from shuffled tuning curves for the three training conditions; uniformly distributed positive values (greater than zero) reflect a tendency for cells to have similar baseline firing rates across sessions. (D) Left column: graphs show scatter plots of each rat’s place tuning stability scores (S); means did not differ significantly from zero. Results for L, C, and R track zones are shown top, middle, and bottom rows, respectively. Middle columns: boxplots show median and range of template-selected population vector correlation bins in each rat. Right column: templates used to select peri-diagonal correlation values from the L, C, and R track zones.