Sleep strengthens integration of spatial memory systems

Spatial memory comprises different representational systems that are sensitive to different environmental cues, like proximal landmarks or local boundaries. Here we examined how sleep affects the formation of a spatial representation integrating landmark-referenced and boundary-referenced representations. To this end, participants (n = 42) were familiarized with an environment featuring both a proximal landmark and a local boundary. After nocturnal periods of sleep or wakefulness and another night of sleep, integration of the two representational systems was tested by testing the participant''s flexibility to switch from landmark-based to boundary-based navigation in the environment, and vice versa. Results indicate a distinctly increased flexibility in relying on either landmarks or boundaries for navigation, when familiarization to the environment was followed by sleep rather than by wakefulness. A second control study (n = 45) did not reveal effects of sleep (vs. wakefulness) on navigation in environments featuring only landmarks or only boundaries. Thus, rather than strengthening isolated representational systems per se, sleep presumably through forming an integrative representation, enhances flexible coordination of representational subsystems.

Wilson and McNaughton (1994) reported that “… information acquired during active behavior is … reexpressed in hippocampal circuits during sleep….” This observation of experience-dependent neural replay activity in the brain during slow-wave sleep (for review, see O''Neill et al. 2010) forms a keystone in our current understanding of how sleep affects memory consolidation in an active system consolidation process that involves the redistribution of hippocampal memory to extrahippocampal regions (McClelland et al. 1995; Diekelmann and Born 2010; Klinzing et al. 2019). According to theory, the emerging extrahippocampal memory representations are essentially schematic, devoid of specific context-information, and lack minute detail (Lewis and Durrant 2011; Payne 2011; Sekeres et al. 2018). Simultaneously, hippocampal replay strengthens hippocampal memory traces in the short-term following Hebbian learning, leading to improved context memory immediately after sleep compared with wakefulness (van der Helm et al. 2011; Weber et al. 2014). In the present study, we sought to test sleep''s role in establishing higher-level memory representations drawing on the example of spatial memory processing.Inspired by the strong role of the hippocampal formation in human spatial memory (Burgess 2008; Hartley et al. 2014) a number of studies examined effects of sleep specifically on spatial memory consolidation (Peigneux et al. 2004; Orban et al. 2006; Ferrara et al. 2008; Rauchs et al. 2008; Wamsley et al. 2010; Nguyen et al. 2013; Noack et al. 2017). In these studies, participants explored a virtual environment during a learning phase before retention periods of sleep and wakefulness and, later on, engaged in specific retrieval tasks that required to reach a predefined goal location in the environment as fast as possible. Results were mixed with, some studies reporting positive effects of sleep on spatial navigation performance (e.g., Peigneux et al. 2004; Wamsley et al. 2010; Nguyen et al. 2013; Noack et al. 2017), whereas in others such sleep effect depended on the length of the retention interval (e.g., Ferrara et al. 2008), or was completely absent (Orban et al. 2006; Rauchs et al. 2008). Interestingly, in the latter studies—despite absent behavioral effects—using a 72-h retention interval between learning and retrieval testing, functional magnetic resonance imaging (fMRI) suggested that sleep favors a shift from activation of hippocampal areas toward preferential activation of striatal areas at retrieval of the relevant spatial representations.Indeed, spatial navigation can rely on two distinct representational systems that involve as key structures hippocampal and striatal circuitry, respectively, and are also linked to different spatial frames of reference (Burgess 2008; Hartley et al. 2014). Doeller et al. (2008) showed in humans that striatal activation is linked to the processing of single proximal landmarks whereas hippocampal activation is related to the processing of spatial boundaries, and that acquisition of representations in both systems may follow different learning rules (Doeller and Burgess 2008). The subject''s reliance on one or the other representation system depends on the specific navigational problem (Maguire et al. 1998; Hartley et al. 2003) as well as familiarity with the environment (Hartley et al. 2003; Iaria et al. 2003; Packard and McGaugh 1996), but both systems can also be activated in parallel and interact. For example, patients with hippocampal atrophy showed impaired memory performance not only for boundary-based but also for landmark-based navigation (Guderian et al. 2015) suggesting the presence of synergistic effects between the representational systems. The activation of the representational systems is presumably coordinated by the medial prefrontal cortex (Ragozzino et al. 1999; Doeller et al. 2008; Rich and Shapiro 2009), that is, a region that is not only involved in the abstraction of schema-like spatial representations (Tse et al. 2011; van Buuren et al. 2014) but, also shows neuronal reactivation during sleep (Euston et al. 2007; Peyrache et al. 2009).In fact, there is first evidence suggesting that sleep supports the formation of abstract representations of space in particular. We found, for example, that sleep benefitted the extraction of semantic structure (regions defined by semantic category of landmarks) in a virtual navigation task (Noack et al. 2017). To date, there is no study, however, to specifically test the interaction between landmark- and boundary-referenced representations of space and their integration during sleep. Here we sought to fill this gap. Drawing on the active systems consolidation concept of sleep (Dudai et al. 2015; Klinzing et al. 2019) and on the existing literature, we followed the hypothesis that, rather than benefiting a specific spatial representation, sleep via neuronal replay primarily supports the formation of an integrative schema-like spatial representation and, thereby, improves flexibility in the use of hippocampus-based and striatum-based representations.To this end, we conducted two experiments, a Main experiment and a Control experiment, using a virtual spatial environment with one proximal landmark and a local boundary (Fig. 1) to preferentially engage striatum and hippocampus-based representational systems, respectively (Doeller et al. 2008). The Main experiment was designed to test the effect of sleep on the integration of landmark-referenced and boundary-referenced representations of space. To this end, participants were first familiarized with an environment featuring both a landmark and a boundary, thereby encoding both hippocampal as well as striatal representations of the environment. In order to test whether sleep enhances the integration of these representations, participants either slept or remained awake on the night after the Familiarization phase. They then learned new objects in impoverished environments featuring the same spatial cues (landmark and boundary) at the same locations but only one at a time. At a final Test session, the integration of the combined environmental layout including landmark and boundary (as presented during Familiarization before sleep) was investigated by the participant''s flexibility to switch from landmark-based to boundary-based navigation in the environment, and vice versa, from boundary-based to landmark-based navigation (Fig. 1). In the Control experiment, we investigated the direct effect of postlearning sleep or wakefulness on the consolidation of spatial memory representation that were either merely boundary-referenced or landmark-referenced, thereby controlling for general effects of sleep on spatial memory performance.Open in a separate windowFigure 1.Task and general procedures. (A) Example views on the three different environments. (Panel i) landmark and boundary present, as used in the Familiarization phase of the Main experiment. Alpine environment (panel ii), and Desert environment (panel iii) as used in the Control experiment. (B) Task procedure: The task featured three different trial types in both experiments. (Panel i) Acquisition trials were presented at the start of Familiarization and Learning phases in both experiments. (Panel ii) Feedback and Test trials started with the presentation of an object on a gray screen. Participants were then placed in the experimental environment containing boundary (thick encirclement), landmarks (traffic cone) or both, and dropped the object at the location where they found it during acquisition. In Feedback trials feedback was given by presenting the object at its correct location. Participants navigated to it to collect it. (C) Design of Main experiment: Environment featured both landmark and boundary cues during Familiarization. The Test session comprised Learning phase and Retrieval phase. Only one spatial cue (landmark or boundary) was present during each trial of the Learning and Retrieval phase (three objects with landmark, three objects with boundary). Object reference switched from Learning to Retrieval phase: Objects presented together with the landmark during learning were presented with boundary during retrieval and vice versa. Note that a specific spatial cue was always at the same relative position when presented during Familiarization, Learning, and Test. (D) Design of Control experiment: Participants were randomly assigned to the Boundary or the Landmark group, whereas all participants performed in Wake and Sleep condition. Each of the two visits (sleep and wake) consisted of two sessions (learning: six Acquisition trials + four blocks and six feedback trials; retrieval: three blocks and six Test trials).To preview our results: Whereas there was no effect of sleep on landmark- and boundary-referenced spatial memory per se in the Control experiment, sleep indeed facilitated the flexible use of different spatial retrieval cues possibly based on a superior integrated spatial memory representation.