The hippocampal sharp wave-ripple in memory retrieval for immediate use and consolidation

Abstract

Various cognitive functions have long been known to require the hippocampus. Recently, progress has been made in identifying the hippocampal neural activity patterns that implement these functions. One such pattern is the sharp wave-ripple (SWR), an event associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Hippocampal spiking during SWRs can represent past or potential future experience, and SWR-related interventions can alter subsequent memory performance. These findings and others suggest that SWRs support both memory consolidation and memory retrieval for processes such as decision-making. In addition, studies have identified distinct types of SWR based on representational content, behavioural state and physiological features. These various findings regarding SWRs suggest that different SWR types correspond to different cognitive functions, such as retrieval and consolidation. Here, we introduce another possibility - that a single SWR may support more than one cognitive function. Taking into account classic psychological theories and recent molecular results that suggest that retrieval and consolidation share mechanisms, we propose that the SWR mediates the retrieval of stored representations that can be utilized immediately by downstream circuits in decision-making, planning, recollection and/or imagination while simultaneously initiating memory consolidation processes.

Fig. 1 |. Schematic of sharp wave-ripple rate across brain state and with movement speed.

In the awake state, the sharp wave-ripple (SWR) rate varies as a function of movement speed, novelty and receipt of reward. SWRs are most common during periods of immobility and become increasingly rare at higher movement speeds. Their rate is higher across all speeds in novel versus familiar environments, and in both novel and familiar environments their rate is highest following receipt of reward. During sleep, SWRs occur only rarely during rapid eye movement (REM) sleep and occur most often during slow-wave sleep. The SWR rate during slow-wave sleep (in a familiar sleep box) following exploration of a novel environment is higher than it is following exploration of a familiar environment. The SWR rate in REM sleep has not been studied following experience in a novel environment, therefore it is omitted from the figure. These patterns of modulation are consistent with an increased SWR rate during and after learning and indicate that SWR-mediated retrieval is utilized primarily at lower speeds.

Fig. 2 |. Schematic of possible local replays: in the forward and reverse directions, centrifugally and centripetally.

Place cells increase their firing rates as a rat traverses the cells’ respective place fields on a linear track from left to right (orange to purple). When the rat pauses, immobile, at the centre of the track, a sharp wave-ripple (SWR) occurs. Place cell activity during the SWR recapitulates recent experience, firing in the same order on a compressed timescale. Relative to the order of place cell firing during actual experience, these sequences can represent trajectories that are forward and centripetal (towards the rat); reverse and centrifugal (away from the rat); forward and centrifugal; or reverse and centripetal. Forward sequences are indicated by arrows beside the label ‘forward’ that are oriented in the same direction as the trajectory arrow (in this case rightward); reverse sequences, by contrast, are indicated by arrows in the direction opposite to the trajectory arrow. For centrifugal sequences, these arrows are oriented away from the rat; for centripetal sequences, the arrows are oriented towards the rat. If any of these sequences occurred before the rat actually traversed that track segment (as occurs more often in a less constrained environment with more path options), they would represent novel sequences. A second set of place cells with overlapping place fields, but that are preferentially active when the rat moves in the opposite direction (right to left), would participate in the same four replay types. If the rat ran on the track (middle panel), then the replays (top row) occurred when the rat was no longer on the track, and they would be classified as remote.

Fig. 3 |. Hypothesized function for sharp wave-ripples in retrieval of information from memory for immediate use and consolidation.

We hypothesize that retrieval, as it occurs here as the rat pauses on approach to a choice point, can be mediated by the sharp wave-ripple (SWR) (left panel, lower box), during which the ordered reactivation of place cells can represent trajectories previously experienced by the animal. Here, a centrifugal forward replay composed of activity from place cells with fields shown in purple to red is depicted (left panel, middle box). Nodes (left panel, top box) represent recorded hippocampal cells, and coloured nodes represent those place cells that spiked during the replay; they do not, as is true for many detected replay events, correspond to all the cells that likely participate in the replay event. The effect of replay activity in the hippocampus is the reactivation of activity in distributed networks outside the hippocampus (for example, the cortex; middle; red nodes indicate active neurons). The immediate effect of this on behaviour (top right) is to enable computations for decision-making leading to action; in this case, selection of the trajectory option that was not replayed. We propose that another long-term effect (bottom right) is the initiation of consolidation processes that can maintain (solid black lines), form (dashed red lines), strengthen (solid red lines) or renormalize (dashed black lines) synapses within the hippocampus, between the hippocampus and the cortex or within the cortex. Which of these effects will occur likely depends on neuromodulatory and other factors, subject to plasticity rules. We show here examples of possible changes: strengthened (solid red lines) or newly formed (dashed red lines) synaptic connections between pairs of active cells in the cortex (red nodes), between cells in the hippocampus (coloured nodes) or between cells in the hippocampus and cortex as well as weakened synaptic connections between cell pairs where one or both was inactive (white nodes). The maintenance of synaptic strength may also be supported by the SWR, potentially between any combination of active and inactive cells. The effect of these changes, which may contribute to systems consolidation, is to facilitate future retrieval events. It is possible that strengthened intracortical synapses could also eventually support memory retrieval independent of the hippocampus.