Hippocampal replay reflects specific past experiences rather than a plan for subsequent choice

Abstract

Executing memory-guided behavior requires storage of information about experience and later recall of that information to inform choices. Awake hippocampal replay, when hippocampal neural ensembles briefly reactivate a representation related to prior experience, has been proposed to critically contribute to these memory-related processes. However, it remains unclear whether awake replay contributes to memory function by promoting the storage of past experiences, facilitating planning based on evaluation of those experiences, or both. We designed a dynamic spatial task that promotes replay before a memory-based choice and assessed how the content of replay related to past and future behavior. We found that replay content was decoupled from subsequent choice and instead was enriched for representations of previously rewarded locations and places that had not been visited recently, indicating a role in memory storage rather than in directly guiding subsequent behavior.

Keywords: consolidation; decoding; hippocampus; learning; memory; navigation; planning; replay; sharp wave ripples.

Figure 1.. Rats learn to perform a flexible spatial memory task.

(A) Overhead view of the track layout, consisting of eight outer arms ending in reward ports and a central “box” area containing the home and center ports. Each trial consists of the three steps illustrated. (B) Schematic illustrates the arm choices of the rat across the two trial types, search and repeat, that make up each block of trials. (C) Expanded series of trials from an example behavioral session including more than 4 complete trial blocks. Trials which contain any deviation from proper visit order (timeouts; grey shading) are excluded from analysis. (D) Boxplot of trial blocks completed per behavioral session for each subject; n = 24, 32, 23, and 33 sessions per subject, respectively. (E) Average outer arm reward rate of the 4 subjects aligned to the first trial after the goal location has changed. (F) Average outer arm reward rate aligned to the first trial after the first reward is received at a new goal location. For (E) and (F), dotted line indicates chance performance level of 0.125 corresponding to a random choice out of eight possible arms. Shading indicates binomial S.E.M. across trial blocks; n = 89, 85, 105, and 166 trial blocks per subject, respectively.

Figure 2.. Decoding replay content during SWRs.

(A) 2D position is linearized by converting each maze area into a linear segment. Orange trace indicates the 2D (left) and 1D (right) position tracking for a single trial; linearized maze segments are separated by dashed lines. SWR events are indicated in blue. Arrowheads indicate the example SWRs shown in panels (C-D) and the example movement period (grey shading) shown in (B). (B) Decoded position for the movement period as the animal runs from a center port to the end of arm 5. Representative CA1 LFP trace is shown above. (C, D) Two examples of spatially continuous remote replay events occurring during the single trial illustrated in (A); SWR detection boundaries are indicated with blue shading and representative CA1 tetrode LFP is included above. (E) Example of a spatially continuous local event in which decoded position is the same as the actual position. (F) Quantification of the fraction of all detected SWRs that are categorized as remote. Boxplot range reflects variability in remote event fraction across sessions; n = 24, 32, 23, and 33 sessions per subject, respectively.

Figure 3.. Replay is consistently enriched for previous goal arms.

(A) Pie charts for each subject illustrate the proportion of spatially continuous replay events that occur in the box or at arm ports by their content. (B) Left, boxplots of the fraction of remote replay events in the box area that represent the past, future, previous goal, or other arms during a subset of search phase trials in which past, future, and previous goal arms are distinct. Boxplot range reflects the variability in remote event fractions across sessions; only sessions with at least 5 trials that met the distinct arm criteria were included. N = 22, 23, 16, and 26 sessions per subject, respectively. Significance was calculated relative to a random distribution which was matched for remote event numbers per session for each subject using Wilcoxon rank-sum test. * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001. Right, total fraction of remote events corresponding to arms in the “other” category. (C) As in (B) but using a subset of repeat trials when the past, future, and goal arms are the same and the previous goal arm is distinct. N = 23, 30, 22, and 31 sessions per subject, respectively. (D) Fold change of remote replay rate given arm identity of the past, future, or previous goal based on GLM model. Lines represent 99% confidence interval; n = 711, 848, 725, and 1065 trials per subject; 8 entries per trial. (E) As in (D), but for repeat trials; n = 1347, 1661, 1154, and 1730 trials per subject; 8 entries per trial.

Figure 4.. Replay of current goal increases with experience.

(A) Fold change of remote replay rate given arm identity of the past, future, current goal or previous goal based on GLM fit to repeat trials that occur while the subject has received less than five rewards at the current goal location. Lines represent 99% confidence interval; n = 594, 801, 573, 793 trials per subject; 8 entries per trial. (B) Same as (A) for trials when the subject has earned five or more rewards at the current goal location. N = 801, 895, 600, and 967 trials per subject; 8 entries per trial. (C) Replay rate of the current goal on correct repeat trials stratified by the amount of reward experience the subject has had at the current goal location. Points represent an average of all trials with the indicated reward history; only groups containing at least ten trials are plotted. Range of trials per point: 16-90, 33-87, 10-106, and 13-171 per subject, respectively.

Figure 5.. Upcoming behavior is unrelated to replay of the future, current goal, or previous goal.

(A) Future replay per trial tends to occur less than once per trial, and more often during search trials than repeat trials for three of the four subjects. N = 534, 617, 570, and 879 search trials and 924, 1019, 894, 1302 repeat trials per subject, respectively. Search vs repeat rate p = 0.001, 5.002e-11, 0.264, and 4.111e-5 for each subject, respectively, using Wilcoxon rank-sum test. (B) Rate of future arm replay during the repeat phase on correct (solid) compared to error (shaded) trials. (C) Rate of current goal replay during the repeat phase on correct (solid) and error (shaded) trials. For (B) and (C), n = 923, 1007, 847, and 1340 correct trials and 424, 654, 307, and 390 error trials per subject, respectively. (D) Cross-validated predictions of correct or error trials are at or very near chance levels. For each subject, a five-fold cross-validated binomial GLM is fit and used to predict correct and error trials based on the number of future replay events, the number of current goal replay events, or the number of events in future, past, current goal, and previous goal categories. Trials are subsampled to match the numbers of correct and error trials such that chance classification rate is 50%; n = 848, 1308, 614, and 780 trials per subset per subject, respectively. Inset is an expanded view around 50%; lines represent 99% confidence intervals reflecting the variability over 1000 subsamples drawn from the full dataset. (E) Fraction of all trials which include replay of the previous goal preceding a visit to the previous goal arm (solid) or preceding a visit to any other arm (shaded). N = 23, 32, 23, and 33 sessions per subject, respectively. For (B), (C), and (E), significance was calculated using Wilcoxon rank-sum test; ** indicates p<0.01; *** indicates p<0.001. Error bars for all panels represent S.E.M.

Figure 6.. Replay of previous goal continues long after behavior changes.

(A) Mean replay rate curve of a particular goal location for each subject aligned to the last rewarded trial of that goal’s block of trials. Solid line indicates replay rate of the goal arm; dashed line represents replay rate of non-rewarded arms during the same span of trials. (B) Mean visit rate to the goal (solid) or non-goal (dashed) arms aligned to the same span of trials as (A). For (A) and (B), shading indicates S.E.M. (C) Mean replay rate of goal and non-goal arms over search (s) and repeat (r) sub-blocks for the three trial blocks after a particular goal location has changed. Error bars represent S.E.M. For all panels, red dots indicate which comparisons exceed a 0.05 significance threshold after Bonferroni correction for multiple comparisons (80 comparisons each for (A) and (B); 6 comparisons for (C)). Data included from 89, 85, 104, 161 goal arms and 347, 437, 268, 397 unrewarded arms per subject, respectively.

Figure 7.. Replay of unrewarded arms is biased toward non-recent past.

During search trials, the replay rate of arms that have never been rewarded are categorized based on whether they were visited 1, 2, 3, 4, or 5 trials ago. Error bars indicate S.E.M. over trials; statistical comparisons were calculated between the five trials ago condition and each other bar. * indicates p<0.05; ** indicates p<0.01; *** indicates p<0.001; trials per bar range from 159-433, 212-555, 144-386, and 198-520 trials per subject, respectively.

Figure 8.. Replay at the outer arm ports.

(A) Fraction of non-box events at rewarded outer arm ports that correspond to the current arm, the previous goal, or any other arms during the subset of trials when the past, current arm, and goal arm are the same and distinct from the previous goal arm. N=333, 958, 1161, 3316 events per subject, respectively. (B) Fold change of arm replay rate given arm identity of current arm/past arm/goal, the previous goal, or any other arms based on GLM model. Lines represent 99% confidence interval; n=948, 1026, 868, 1372 trials per subject; 8 entries per trial.