Awake replay of remote experiences in the hippocampus

Abstract

Hippocampal replay is thought to be essential for the consolidation of event memories in hippocampal-neocortical networks. Replay is present during both sleep and waking behavior, but although sleep replay involves the reactivation of stored representations in the absence of specific sensory inputs, awake replay is thought to depend on sensory input from the current environment. Here, we show that stored representations are reactivated during both waking and sleep replay. We found frequent awake replay of sequences of rat hippocampal place cells from a previous experience. This spatially remote replay was as common as local replay of the current environment and was more robust when the rat had recently been in motion than during extended periods of quiescence. Our results indicate that the hippocampus consistently replays past experiences during brief pauses in waking behavior, suggesting a role for waking replay in memory consolidation and retrieval.

Figure 1

a, Overview of experimental design. Each day of recording consisted of two 15 minute exposures to Environment 1 (E1) followed by one 15 minute exposure to Environment 2 (E2). Each exposure was flanked by 20 minute rest sessions in the rest box. The total size of each W-track was 76 cm square, and the width of the arms was 7 cm. The rest box was 25 × 34 cm. b, Distinct spatial representations for E1 and E2. Each column shows the spatial rate maps for one neuron for both E1 (top row) and E2 (bottom row). The number to the upper right of each plot corresponds to the maximum rate displayed for that cell which was 65% of the neuron’s peak spatial rate. The color bars to the right illustrate the range of colors that are mapped from 0 to the maximum displayed rate. Rates are rounded to the nearest whole number. The plots show 10 of 33 simultaneously recorded neurons with E1 and/or E2 place fields from animal 3, day 8.

Figure 2

Spatially remote awake replay in the rest box. a, Spike rasters (black) from 18 cells active in E1 along a correct and a subsequent incorrect trajectory. The same cells and associated numbers are used in all panels. The red line shows the animal’s linear distance during the same period, and the W-track cartoons below show the specific locations the animal traversed. b, 2D spatial rate maps for the E1 place cells active in (a). c, The animal’s trajectory during and after a replay event. Grey dots represent all sample locations, the yellow circle represents the animal’s location during the SWR and the green dots represent the animal’s location in the five seconds following the SWR. Here the animal was still for more than five seconds before the SWR, but in other figures red dots represent the locations during the five seconds before the SWR. d, Sequential spiking during the SWR. Bottom: rasters of all E1 place cells that were activated during the SWR. Top: the filtered LFP signal from one tetrode. The color bar shows the colors associated with each of the 15 ms decoding bins. e, Decoded locations for each bin. Each colored line represents the probability distribution resulting from decoding the spiking in the associated 15 ms period from (d). f, A cartoon of the replayed trajectory in E1. g–j, k–n. Examples of awake replay of E1 in the rest box. The motion before and after the events demonstrates that the animal was awake.

Figure 3

Replay of E1 in the rest box is more robust during awake than quiescent periods. a, The proportion of significant replay events was similar in E1 and during awake periods in the rest box (R awake), but was lower during quiescence in the rest box (R quiesc.; p < 0.001). b, Scatter plot of the firing rate of all neurons with place fields in E1 during awake and quiescent SWRs in the rest box. Rates for the large majority of neurons were higher during quiescence (p < 10⁻¹⁰). c, Histogram of the proportions of SWRs during awake and quiescent periods with different numbers of cells active. Awake SWRs were more likely to activate a larger number of cells as compared to while quiescent SWRs (p < 10⁻¹⁰). d, Pair-wise reactivation in the rest box. Each plot shows rows representing the normalized cross-correlegrams between all pairs of simultaneously recorded neurons with place fields in E1, with the vertical location of each row determined by the distance between the two cells place field peaks in E1. The ‘V’ representing activation consistent with replay is more clearly visible in the awake state, and the R² value representing the degree to which the times between spikes from two neurons predict the distances between the peaks of their place fields was significantly larger for awake replay events.

Figure 4

Robust replay of E1 while the animal was located in E2. a, The location of the animal in E2 during an E1 replay event. b, Spiking during a SWR representing replay which decodes (c) to a coherent trajectory in E1 (d). See Fig. 2c–e for a detailed description of each element of the plots. For this event the animal was still for > 5 seconds before and after the SWR, so only the animal’s location is shown in (a). e, f, Activation of neurons with place fields in E2 during the same SWR event and the decoded locations for E2. The neural activity during the SWR involved a coherent replay of E1 but not of E2. Cells are not numbered because different subsets cells are shown in each panel, but cells with place fields in both E1 and E2 and are shown in both raster plots. See Supplementary Fig. 5 for this event and the associated 2D spatial rate maps. g – l. A second example illustrating replay of E1 in the absence of replay of E2. See Supplementary Fig. 6 for this event and the associated 2D spatial rate maps. See Supplementary Clusters for the cluster plots associated with each cell with a place field in E1. m, Pair-wise sequential activation plot for E2 SWRs including only neurons with place fields in E1 but not in E2. See Fig. 3d for an explanation of the plot. The associated R² value was 0.17, indicating activity consistent with replay.

Figure 5

Local spatial rate and replay initiation for E1 replay in E2 and the rest box. The first cell active in each SWRs had a higher local spatial rate in E2 and for awake (< 5 seconds immobile), but not quiescent (> 5 seconds immobile) events in the rest box. Error bars represents the mean ± 25^th percentiles. * represents p < 0.05, ** represents p < 0.002.