Extended Data Fig. 2: Quantification of remapping types and controls for reward-relative remapping. | Nature Neuroscience

Extended Data Fig. 2: Quantification of remapping types and controls for reward-relative remapping.

From: A flexible hippocampal population code for experience relative to reward

Extended Data Fig. 2

a) Example cells from 2 additional mice (top: m14, bottom: m12; Env 2, day 14), replicating the co-existence of remapping types within animal shown in Fig. 2a. Orange labels, “reward-relative” cells. b) Example smoothed 2D histograms of the fraction of place cells in mouse m14 with peak firing in each 10 cm bin before vs. after the reward zone switch (or in the 1st vs. 2nd half of trials on “stay” days), for a “stay” day (day 6, same reward location, same environment), “switch within” day (day 7, change reward location, same environment), or “across environment” day (day 8, change reward location, change environment). White lines, reward zone starts. Only cells with significant spatial information both before and after are included. A strong density along the diagonal on the “stay” day indicates place cells that remain track-relative throughout the session. On switch days, this diagonal degrades as more cells remap, and the off-diagonal band around the reward intersection appears (see also Fig. 2c). When the environment changes, the diagonal degrades further indicating more global remapping, but the reward-relative band is maintained. Cyan boxes, bins used for the “diagonal” and “near reward” categories shown in (c). c) Quantification of remapping using bins of the histograms illustrated in (b) (unsmoothed for quantification). Each dot is the mean fraction of cells across days of each type per animal (n = 11 mice); horizontal lines, median across mice. In (c, d), *p < 0.05, **p < 0.01, ***p < 0.001 from pairwise, paired two-sided t-tests between categories (“stay”, “switch within”, “across env”), performed on the logit-transformed fractions, Holm-corrected for multiple comparisons within subpanel. “Near reward”: cells with peaks ≤50 cm from both reward zone starts; gray dashed box: fraction of total place cells near the reward on stay days across the 1st to 2nd half of the session, thus no t-tests are shown for this category as the reward is not moved. Switch within vs. across env: t = −2.9, p = 0.015. “Diagonal”: peaks within ≤50 cm of the same linear position before vs. after. Stay vs. switch within: t = 2.2, p = 0.05; stay vs. across env: t = 14.6, p = 1.3e-7; switch within vs. across env: t = 10.7, p = 1.8e-6. “All other remapping”: all bins not near-reward and not along the diagonal. Stay vs. switch within: t = −9.1, p = 7.3e-6; stay vs. across env: t = −27.6, p = 2.7e-10; switch within vs. across env: t = −8.6, p = 7.3e-6. d) Mean fractions of place cells (across days of each type per animal) defined as track-relative, disappearing, appearing, remap near reward, or remap far from reward (see Methods), agnostic of which cells can be described as “reward-relative” since that remapping category cannot be defined on stay days. Track-relative: stay vs. switch within: t = 5.6, p = 2.2e-4; stay vs. across env: t = 23.4, p = 1.4e-9; switch within vs. across env: t = 9.1, p = 7.7e-6. Disappearing: stay vs. switch within: t = −3.4, p = 0.022; stay vs. across env: t = −2.8, p = 0.035; switch within vs. across env: t = −1.3, p = 0.23. Appearing: stay vs. switch within: t = −4.1, p = 0.0022; stay vs. across env: t = −9.6, p = 7.0e-6; switch within vs. across env: t = −5.5, p = 5.2e-4. Remap near reward: switch within vs. across env: t = 0.86, p = 0.41. As in (c), gray dashed box: fraction near reward on stay days without a reward switch, thus no statistical comparisons are shown. Remap far from reward: stay vs. switch within: t = −6.7, p = 1.5e-4; stay vs. across env: t = −4.6, p = 0.0020; switch within vs. across env: t = −0.67, p = 0.52. e) To test whether reward-relative neurons encode distance traveled since the last reward, we asked whether distance run in the variable length teleport period predicted an offset in the cell’s peak spatial firing (error from its mean) on the subsequent trial. Example reward-relative cell (cell m14.482 on day 8, switch 4; also shown in Fig. 2b), with no significant Spearman correlation between the teleport distance run and signed spatial peak error for either set of trials (dots). Blue, trials before the switch: r = 0.10, p = 0.59; Pink, trials after the switch: r = −0.14, p = 0.34. f) Spearman correlation coefficients between teleport distance run and spatial peak error on the subsequent trial, for all reward-relative cells (n = 5979 cells, 11 mice, 7 switch days). Histograms are stacked; dark shades, significant cells (p < 0.05): 6.7% of reward-relative cells on before trials, 7.5% on after trials. Light shades, non-significant cells: 93.3% of reward-relative cells on before trials, 92.5% on after trials. g) Histograms of the circular difference between relative peaks after minus before the switch for remapping place cells on switch days not shown in Fig. 2e, g (n = 11 mice; day 5 n = 997 cells, day 7 n = 1128 cells, day 8 n = 1157 cells, day 10 n = 1022 cells, day 12 n = 934 cells). h) Increase in above-chance reward-relative remapping across experience, at the level of individual animals. Each point, fraction of cells (logit-transformed) exceeding the “random-remapping” shuffle calculated within each mouse and switch day (n = 11 mice). Regression coefficient β and p-value (two-sided Wald test) are from a linear mixed effects model with switch index as the fixed effect and mice as random effects. Gray line, model prediction. il) Control for Fig. 2d–g, excluding cells with peaks ≤50 cm (~0.698 radians) from both reward zone starts (a 100-cm span, indicated by magenta lines). (i) n = 888 cells, 11 mice. (k) n = 795 cells, 11 mice. (j, top) and (l, top): The fraction of cells remapping relative to reward at distances greater than ±50 cm still exceeds the shuffle. (j, bottom) and (l, bottom): distribution of mean reward-relative positions for the cells in the orange shaded region around the unity line in (i) and (k), respectively. (j) significant non-zero mean = 1.145, 95% confidence interval [lower, upper]=[0.822, 1.468], circular mean test, n = 285 cells. (l) significant non-zero mean = 1.245, 95% confidence interval [lower, upper] = [0.931, 1.559], circular mean test, n = 303 cells. Note that cells firing within 50 cm of one reward but not the other may have a circular mean relative distance of <0.698 radians (<50 cm), visible as the small fractions between the magenta lines. m) Fraction of reward-relative cells (mean ± SEM across mice) with peak firing before (gray) or after (black) the reward zone start, following exclusion of cells within iteratively larger regions on either side of reward (that is, an exclusion distance of 10 cm is a 20 cm span around the reward zone start). *p < 0.00263 significance level with Bonferroni correction, two-sided z-test for proportions compared to a null hypothesis of a 50/50% split: First switch: 10 cm: p = 1.2e-17, 20 cm: p = 5.4e-12, 30 cm: p = 5.2e-7, 40 cm: p = 7.9e-7, 50 cm: p = 0.00014; Last switch: 10 cm: p = 5.4e-35, 20 cm: p = 1.0e-20, 30 cm: p = 1.1e-15, 40 cm: p = 3.9e-13, 50 cm: p = 3.1e-9, 60 cm: p = 3.4e-8, 70 cm: p = 9.3e-6, 80 cm: p = 0.000256. n) After excluding cells within 50 cm of the reward zone start, the fraction of reward-relative remapping cells above the shuffle shows a trending but non-significant increase across task experience. Gray line and shading, best fit ± SD of linear regression. o) Illustration of cross-correlation criterion to identify reward-relative (RR) (top row) vs. track-relative (TR) (middle row) vs. non-reward-relative (non-RR) remapping cells (bottom row). Each cell is also shown in (a, top row). Left column: cross-correlation (xcorr) between trial-averaged spatial firing with reward zones circularly aligned (middle column), before vs. after the switch. Gray lines, mean (solid) and 95% confidence interval (dashed) of the shuffle per cell. Listed at left: offset of the xcorr maximum above the shuffle, distance between relative peaks in radians. Teal line, reward zone switch trial. Right column: trial-by-trial correlation matrix using reward-aligned activity. Note the uniform structure for the RR cell vs. the block-like matrices for the TR and non-RR remapping cell, opposite of how these matrices appear in original linear track coordinates (a, top row). p) Left: Two-sided Pearson correlation coefficients for each subpopulation across 11 mice and 7 switch days, between each cell’s trial-averaged activity maps pre- vs. post-switch in reward-aligned coordinates. Two-sided Wilcoxon rank-sum tests: RR vs. TR: Z = 91.7, p < 1e-24 (n = 5979 RR cells, 7027 TR cells); RR vs. non-RR remapping: Z = 71.6, p < 1-e24 (n = 5979 RR cells, 4314 non-RR cells). Right: Maximum xcorr offsets above the shuffle for each subpopulation, with the RR distribution thresholded at ±5 bins. q) Same as (p), but using trial-averaged activity of each subpopulation in original linear track coordinates. Two-sided Wilcoxon rank-sum tests: TR vs. RR: Z = 94.3, p < 1e-24; TR vs. non-RR remapping: Z = 26.2, p < 1e-24.

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