Distinct preplay of multiple novel spatial experiences in the rat

Abstract

The activity of ensembles of hippocampal place cells represents a hallmark of an animal's spatial experience. The neuronal mechanisms that enable the rapid expression of novel place cell sequences are not entirely understood. Here we report that during sleep or rest, distinct sets of hippocampal temporal sequences in the rat preplay multiple corresponding novel spatial experiences with high specificity. These findings suggest that the place cell sequence of a novel spatial experience is determined, in part, by an online selection of a subset of cellular firing sequences from a larger repertoire of preexisting temporal firing sequences in the hippocampal cellular assembly network that become rapidly bound to the novel experience. We estimate that for the given context, the recorded hippocampal network activity has the capacity to preplay an extended repertoire of at least 15 future spatial experiences of similar distinctiveness and complexity.I t is a matter of debate whether specific sequences of place cells(1) encoding different novel spatial experiences in the rat are formed exclusively during the experiences (2-4) or are, in part, preconfigured in the form of correlated temporal sequences that are expressed before the experience (5-7). Previous work in mice has shown that in the naïve animal, temporal firing sequences expressed in association with sharp-wave ripples during sleep or rest can preplay future spatial sequences of place cells encoding novel environments (5). However, it remains unclear whether place cell sequences encoding a novel spatial experience are preconfigured as a dominant cluster of temporal sequences preferentially preplaying the subsequent experience or whether they are selected from an existing larger repertoire of temporally organized sequences. The latter would confer the hippocampal network with the capacity to rapidly encode multiple parallel spatial experiences, but the extent of this capacity has not been addressed experimentally. Here we investigate these two issues. Results Preplay of Future Place Cell Sequences and Spatial Trajectories.Ensembles of place cells were recorded from the CA1 area of the hippocampus in three experimentally naïve rats during sleep/ rest sessions and during subsequent first-time exploration of 1.5-m-long linear tracks (Fig. 1A). The sleep/rest sessions were conducted in a sleep/rest box surrounded by high opaque walls that blocked the rats' view of the room except for a limited portion of the ceiling. After the naïve rats went through an ∼1-h sleep/rest period, a linear track (Materials and Methods) was introduced into the room for the first time. Place cell sequence templates were computed by ordering the place cells based on the location of their place field peak firing during exploration of the linear track (Fig. 1B, Right). Spiking events were detected during sleep/rest frames (8) as epochs of multiunit activity recorded from at least six different pyramidal cells with a <100-ms interspike interval in the multiunit activity, flanked by epochs of >...

Selection of preconfigured cell assemblies for representation of novel spatial experiences

“…Subsequently, the naive animals ran for the very first time on a linear track and the newly established place cell sequences (figure 2b) were correlated with the temporal sequences fired during the preceding sleep/rest session (figure 2a). Intriguingly, we found significant preplay sequences ( figure 2a,c) for the future place cell sequences (figure 2b) and future spatial trajectories (figure 2d) on the novel track in 7-10% of all spiking events recorded during the preceding sleep in the naive rats [41]. This result demonstrates that the hippocampal network, and likely the remaining brain, is not tabula rasa in the naive animals (figure 3a) but it is preconfigured by default into sequentially active cellular assemblies (figure 3b), possibly as a result of previous, spatially unstructured experiences.…”

“…The preconfigured hippocampal network during sleep/ rest was able to preplay multiple, distinct, parallel spatial experiences as early as 6-8 h before the actual spatial experiences would occur [41]. Using three individual tracks connected in a letter 'U' shape, we were able to show the existence of three separate clusters of temporal sequences that individually preplayed each of the three tracks with very high specificity, 90% on a pair of novel tracks [41].…”

“…In a recent set of experiments, we investigated whether temporally structured activity exists in the hippocampal network of experimentally naive animals during sleep and rest and whether the temporal pattern of that activity is predictive or correlated with the pattern of cellular activation during repeated runs on a novel linear track [24,41]. Prior to our experiments, the dominant model of hippocampal place cell ensemble activity had postulated that place cell firing order is established for the first time during the exploration to encode the spatial experience, and is subsequently replayed during sleep or rest perhaps to enable the consolidation of the encoded experience [26,27,32,35].…”

“…10%) of awake resting epochs, the temporal order of firing of a mix of silent cells and previously active place cells was predictive of their future order of firing as place cells on a novel linear track [24]. We called this novel phenomenon preplay [24,41] because the predictive temporal sequences preceded the matching place cell sequences on the novel track. The preplay sequences were not a replay of the recent activity because the order in which the previously active place cells fired on the novel track was different from the order in which they had fired during the previous exploration of the familiar track, and the preplay sequences were not correlated with the place cell sequences active on the familiar track [24].…”

“…In order to address this necessity issue, we recently recorded 1-2 h of sleep/rest from naive rats (figure 2a) before they had any visual or physical access to a linear track [41]. Subsequently, the naive animals ran for the very first time on a linear track and the newly established place cell sequences (figure 2b) were correlated with the temporal sequences fired during the preceding sleep/rest session (figure 2a).…”