Two distinct ways to form long-term object recognition memory during sleep and wakefulness.

Memory consolidation is promoted by sleep. However, there is also evidence for consolidation into long-term memory during wakefulness via processes that preferentially affect nonhippocampal representations. We compared, in rats, the effects of 2-h postencoding periods of sleep and wakefulness on the formation of long-term memory for objects and their associated environmental contexts. We employed a novel-object recognition (NOR) task, using object exploration and exploratory rearing as behavioral indicators of these memories. Remote recall testing (after 1 wk) confirmed significant long-term NOR memory under both conditions, with NOR memory after sleep predicted by the occurrence of EEG spindle-slow oscillation coupling. Rats in the sleep group decreased their exploratory rearing at recall testing, revealing successful recall of the environmental context. By contrast, rats that stayed awake after encoding showed equally high levels of rearing upon remote testing as during encoding, indicating that context memory was lost. Disruption of hippocampal function during the postencoding interval (by muscimol administration) suppressed long-term NOR memory together with context memory formation when animals slept, but enhanced NOR memory when they were awake during this interval. Testing remote recall in a context different from that during encoding impaired NOR memory in the sleep condition, while exploratory rearing was increased. By contrast, NOR memory in the wake rats was preserved and actually superior to that after sleep. Our findings indicate two distinct modes of long-term memory formation: Sleep consolidation is hippocampus dependent and implicates event-context binding, whereas wake consolidation is impaired by hippocampal activation and strengthens context-independent representations.

Accelerating Maturation of Spatial Memory Systems by Experience: Evidence from Sleep Oscillation Signatures of Memory Processing.

During early development, memory systems gradually mature over time, in parallel with the gradual accumulation of knowledge. Yet, it is unknown whether and to what extent maturation is driven by discrete experience. Sleep is thought to contribute to the formation of long-term memory and knowledge through a systems consolidation process that is driven by specific sleep oscillations (i.e., ripples, spindles, and slow oscillations) in cortical and hippocampal networks. Based on these oscillatory signatures, we show here in rats that discrete spatial experience speeds the functional maturation of spatial memory systems during development. Juvenile male rats were exposed for 5 min periods to changes in the spatial configuration of two identical objects on postnatal day (PD)25, PD27, and PD29 (Spatial experience group), while a Control group was exposed on these occasions to the same two objects without changing their positions. On PD31, both groups were tested on a classical Object Place Recognition (OPR) task with a 3 h retention interval during which the sleep-associated EEG and hippocampal local field potentials were recorded. On PD31, consistent with forgoing studies, Control rats still did not express OPR memory. By contrast, rats with Spatial experience formed significant OPR memory and, in parallel, displayed an increased percentage of hippocampal ripples coupled to parietal slow oscillation-spindle complexes, and a stronger ripple-spindle phase-locking during the retention sleep. Our findings support the idea that experience promotes the maturation of memory systems during development by enhancing cortico-hippocampal information exchange and the formation of integrated knowledge representations during sleep.SIGNIFICANCE STATEMENT Cognitive and memory capabilities mature early in life. We show here that and how discrete spatial experience contributes to this process. Using a simple recognition paradigm in developing rats, we found that exposure of the rat pups to three short-lasting experiences enhances spatial memory capabilities to adult-like levels. The adult-like capability of building spatial memory was connected to a more precise coupling of ripples in the hippocampus with slow oscillation-spindle complexes in the thalamo-cortical system when the memory was formed during sleep. Our findings support the view that discrete experience accelerates maturation of cognitive and memory capabilities by enhancing the dialogue between hippocampus and cortex when these experiences are reprocessed during sleep.

The hippocampus is crucial for forming non-hippocampal long-term memory during sleep.

There is a long-standing division in memory research between hippocampus-dependent memory and non-hippocampus-dependent memory, as only the latter can be acquired and retrieved in the absence of normal hippocampal function1,2. Consolidation of hippocampus-dependent memory, in particular, is strongly supported by sleep3-5. Here we show that the formation of long-term representations in a rat model of non-hippocampus-dependent memory depends not only on sleep but also on activation of a hippocampus-dependent mechanism during sleep. Rats encoded non-hippocampus-dependent (novel-object recognition6-8) and hippocampus-dependent (object-place recognition) memories before a two-hour period of sleep or wakefulness. Memory was tested either immediately thereafter or remotely (after one or three weeks). Whereas object-place recognition memory was stronger for rats that had slept after encoding (rather than being awake) at both immediate and remote testing, novel-object recognition memory profited from sleep only three weeks after encoding, at which point it was preserved in rats that had slept after encoding but not in those that had been awake. Notably, inactivation of the hippocampus during post-encoding sleep by intrahippocampal injection of muscimol abolished the sleep-induced enhancement of remote novel-object recognition memory. By contrast, muscimol injection before remote retrieval or memory encoding had no effect on test performance, confirming that the encoding and retrieval of novel-object recognition memory are hippocampus-independent. Remote novel-object recognition memory was associated with spindle activity during post-encoding slow-wave sleep, consistent with the view that neuronal memory replay during slow-wave sleep contributes to long-term memory formation. Our results indicate that the hippocampus has an important role in long-term consolidation during sleep even for memories that have previously been considered hippocampus-independent.

Unfolding of spatial representation at systems level in infant rats.

Spatial representations enable navigation from early life on. However, the brain regions essential to form spatial representations, like the hippocampus, are considered functionally immature before weaning. Here, we examined the formation of representations of space in rat pups on postnatal day (PD) 16, using a simple habituation paradigm where the pups were exposed to an arena on three occasions, separated by ~140 min. Whereas on the first two occasions the arena was the same, on the third "test" occasion either proximal cues (Prox group), or distal cues (Dist group), or proximal and distal cues (Prox-Dist group), or no cues (No-change group) were rearranged. Locomotion (distance traveled) was used as behavioral measure of habituation, and c-Fos expression to measure regional brain activity at test. Locomotion generally decreased across the first two occasions. At test, it reached a minimum in the No-change group, indicating familiarity with the spatial conditions. By contrast, the Prox-Dist group displayed a significant increase in locomotion which was less robust in the Prox group and absent in the Dist group, a pattern suggesting that the pups relied more on proximal than distal cues during spatial exploration. c-Fos activity in the No-change group was significantly suppressed in the hippocampus (CA1, CA3, dentate gyrus) but simultaneously enhanced in the prelimbic area (PL) of the medial prefrontal cortex, compared with untreated Home-cage controls, pointing to a possible involvement of the PL in regulating locomotion in familiar spaces. By contrast, in both Prox-Dist and Prox groups c-Fos activity was enhanced in hippocampal CA1 and CA3 regions, suggesting these regions might be particularly involved in regulating exploration of spatial novelty. Our findings show that functional representations of space at a systems level are formed already in pre-weanling rats.

Sleep for preserving and transforming episodic memory.

Sleep is known to support memory consolidation. Here we review evidence for an active system consolidation occurring during sleep. At the beginning of this process is sleep's ability to preserve episodic experiences preferentially encoded in hippocampal networks. Repeated neuronal reactivation of these representations during slow-wave sleep transforms episodic representations into long-term memories, redistributes them toward extrahippocampal networks, and qualitatively changes them to decontextualized schema-like representations. Electroencephalographic (EEG) oscillations regulate the underlying communication: Hippocampal sharp-wave ripples coalescing with thalamic spindles mediate the bottom-up transfer of reactivated memory information to extrahippocampal regions. Neocortical slow oscillations exert a supraordinate top-down control to synchronize hippocampal reactivations of specific memories to their excitable up-phase, thus allowing plastic changes in extrahippocampal regions. We propose that reactivations during sleep are a general mechanism underlying the abstraction of temporally stable invariants from a flow of input that is solely structured in time, thus representing a basic mechanism of memory formation.

Temporal associations between sleep slow oscillations, spindles and ripples.

The systems consolidation of memory during slow-wave sleep (SWS) is thought to rely on a dialogue between hippocampus and neocortex that is regulated by an interaction between neocortical slow oscillations (SOs), thalamic spindles and hippocampal ripples. Here, we examined the occurrence rates of and the temporal relationships between these oscillatory events in rats, to identify the possible direction of interaction between these events under natural conditions. To facilitate comparisons with findings in humans, we combined frontal and parietal surface EEG with local field potential (LFP) recordings in medial prefrontal cortex (mPFC) and dorsal hippocampus (dHC). Consistent with a top-down driving influence, EEG SO upstates were associated with an increase in spindles and hippocampal ripples. This increase was missing in SO upstates identified in mPFC recordings. Ripples in dHC recordings always followed the onset of spindles consistent with spindles timing ripple occurrence. Comparing ripple activity during co-occurring SO-spindle events with that during isolated SOs or spindles, suggested that ripple dynamics during SO-spindle events are mainly determined by the spindle, with only the SO downstate providing a global inhibitory signal to both thalamus and hippocampus. As to bottom-up influences, we found an increase in hippocampal ripples ~200 ms before the SO downstate, but no similar increase of spindles preceding SO downstates. Overall, the temporal pattern is consistent with a loop-like scenario where, top-down, SOs can trigger thalamic spindles which, in turn, regulate the occurrence of hippocampal ripples. Ripples, bottom-up, and independent from thalamic spindles, can contribute to the emergence of neocortical SOs.

Deepened sleep makes hippocampal spatial memory more persistent.

Ample evidence has indicated a beneficial role of sleep, and particularly of slow wave sleep (SWS) in memory consolidation. However, how basic features of sleep, its depth and duration, contribute to this process remained elusive. Here, we investigated spatial object-place recognition (OPR) memory in rats, to systematically dissociate effects of sleep depth and duration on the formation of recent and remote hippocampus-dependent memory. Encoding of the spatial configuration was followed by an experimental post-encoding period of either 2 or 4 h, during which the rats had either "regular sleep", "deeper sleep", or were kept awake. A deeper sleep was achieved by an extended habituation of the rats to the sleep environment. Retrieval was tested either immediately after the 2-hour post-encoding period (recent memory test) or 1 week later (remote memory test). Deeper sleep expressed itself in a selective increase in the time spent in SWS, and in numbers of slow oscillations, spindles, and hippocampal ripples during SWS, whereas preREM and REM sleep were not affected. At the recent test, OPR memory was preserved only after sleep, but independent of its depth. At the remote test, however, OPR memory was preserved only after deeper sleep, whereas the wake and the regularly sleeping rats did not show remote OPR memory, even with the longer 4-h post-encoding period. Our results indicate that, rather than a longer duration, deeper sleep, i.e., a longer time in SWS together with enhanced oscillatory signatures of mnemonic processing during this sleep stage, occurring within a 2-hour window after encoding, is the factor that makes hippocampus-dependent memory more persistent.

Sleep-dependent consolidation patterns reveal insights into episodic memory structure.

Episodic memory formation is considered a genuinely hippocampal function. Its study in rodents has relied on two different task paradigms, i.e. the so called "what-where-when" (WW-When) task and "what-where-which" (WW-Which) task. The WW-When task aims to assess the memory for an episode as an event bound into its context defined by spatial and distinct temporal information, the WW-Which task lacks the temporal component and introduces, instead, an "occasion setter" marking the broader contextual configuration in which the event occurred. Whether both tasks measure episodic memory in an equivalent manner in terms of recollection has been controversially discussed. Here, we compared in two groups of rats the consolidating effects of sleep on episodic-like memory between both task paradigms. Sampling and test phases were separated by a 90-min morning retention interval which did or did not allow for spontaneous sleep. Results show that sleep is crucial for the consolidation of the memory on both tasks. However, consolidating effects of sleep were stronger for the WW-Which than WW-When task. Comparing performance during the post-sleep test phase revealed that WW-When memory only gradually emerged during the 3-min test period whereas WW-Which memory was readily expressed already from the first minute onward. Separate analysis of the temporal and spatial components of WW-When performance showed that the delayed episodic memory on this task originated from the temporal component which also did not emerge until the third minute of the test phase, whereas the spatial component already showed up in the first minute. In conclusion, sleep differentially affects consolidation on the two episodic-like memory tasks, with the delayed expression of WW-When memory after sleep resulting from preferential coverage of temporal aspects by this task.

More Effective Consolidation of Episodic Long-Term Memory in Children Than Adults-Unrelated to Sleep.

Abilities to encode and remember events in their spatiotemporal context (episodic memory) rely on brain regions that mature late during childhood and are supported by sleep. We compared the temporal dynamics of episodic memory formation and the role of sleep in this process between 62 children (8-12 years) and 57 adults (18-37 years). Subjects recalled "what-where-when" memories after a short 1-hr retention interval or after a long 10.5-hr interval containing either nocturnal sleep or daytime wakefulness. Although children showed diminished recall of episodes after 1 hr, possibly resulting from inferior encoding, unlike adults, they showed no further decrease in recall after 10.5 hr. In both age groups, episodic memory benefitted from sleep. However, children's more effective offline retention was unrelated to sleep.

Sleep benefits in parallel implicit and explicit measures of episodic memory.

Research in rats using preferences during exploration as a measure of memory has indicated that sleep is important for the consolidation of episodic-like memory, i.e., memory for an event bound into specific spatio-temporal context. How these findings relate to human episodic memory is unclear. We used spontaneous preferences during visual exploration and verbal recall as, respectively, implicit and explicit measures of memory, to study effects of sleep on episodic memory consolidation in humans. During encoding before 10-h retention intervals that covered nighttime sleep or daytime wakefulness, two groups of young adults were presented with two episodes that were 1-h apart. Each episode entailed a spatial configuration of four different faces in a 3 × 3 grid of locations. After the retention interval, implicit spatio-temporal recall performance was assessed by eye-tracking visual exploration of another configuration of four faces of which two were from the first and second episode, respectively; of the two faces one was presented at the same location as during encoding and the other at another location. Afterward explicit verbal recall was assessed. Measures of implicit and explicit episodic memory retention were positively correlated (r = 0.57, P < 0.01), and were both better after nighttime sleep than daytime wakefulness (P < 0.05). In the sleep group, implicit episodic memory recall was associated with increased fast spindles during nonrapid eye movement (NonREM) sleep (r = 0.62, P < 0.05). Together with concordant observations in rats our results indicate that consolidation of genuinely episodic memory benefits from sleep.

Specific impairment of "what-where-when" episodic-like memory in experimental models of temporal lobe epilepsy.

Episodic memory deficit is a common cognitive disorder in human temporal lobe epilepsy (TLE). However, no animal model of TLE has been shown to specifically replicate this cognitive dysfunction, which has limited its translational appeal. Here, using a task that tests for nonverbal correlates of episodic-like memory in rats, we show that kainate-treated TLE rats exhibit a selective impairment of the "what-where-when" memory while preserving other forms of hippocampal-dependent memories. Assisted by multisite silicon probes, we recorded from the dorsal hippocampus of behaving animals to control for seizure-related factors and to look for electrophysiological signatures of cognitive impairment. Analyses of hippocampal local field potentials showed that both the power of theta rhythm and its coordination across CA1 and the DG-measured as theta coherence and phase locking-were selectively disrupted. This disruption represented a basal condition of the chronic epileptic hippocampus that was linked to different features of memory impairment. Theta power was more correlated with the spatial than with the temporal component of the task, while measures of theta coordination correlated with the temporal component. We conclude that episodic-like memory, as tested in the what-where-when task, is specifically affected in experimental TLE and that the impairment of hippocampal theta activity might be central to this dysfunction.

Hippocampal corticosterone impairs memory consolidation during sleep but improves consolidation in the wake state.

We studied the interaction between glucocorticoid (GC) level and sleep/wake state during memory consolidation. Recent research has accumulated evidence that sleep supports memory consolidation in a unique physiological process, qualitatively distinct from consolidation occurring during wakefulness. This appears particularly true for memories that rely on the hippocampus, a region with abundant expression of GC receptors. Against this backdrop we hypothesized that GC effects on consolidation depend on the brain state, i.e., sleep and wakefulness. Following exploration of two objects in an open field, during 80 min retention periods rats received an intrahippocampal infusion of corticosterone (10 ng) or vehicle while asleep or awake. Then the memory was tested in the hippocampus-dependent object-place recognition paradigm. GCs impaired memory consolidation when administered during sleep but improved consolidation during the wake retention interval. Intrahippocampal infusion of GC or sleep/wake manipulations did not alter novel-object recognition performance that does not require the hippocampus. This work corroborates the notion of distinct consolidation processes occurring in sleep and wakefulnesss, and identifies GCs as a key player controlling distinct hippocampal memory consolidation processes in sleep and wake conditions.

Sleep enhances inhibitory behavioral control in discrimination learning in rats.

Sleep supports the consolidation of memory, and it has been proposed that this enhancing effect of sleep pertains in particular to memories which are encoded under control of prefrontal-hippocampal circuitry into an episodic memory system. Furthermore, repeated reactivation and transformation of such memories during sleep are thought to promote the de-contextualization of these memories. Here, we aimed to establish a behavioral model for the study of such sleep-dependent system consolidation in rats, using a go/nogo conditional discrimination learning task known to essentially depend on prefrontal-hippocampal function. Different groups of rats were trained to criterion on this task and, then, subjected to 80-min retention intervals filled with spontaneous morning sleep, sleep deprivation, or spontaneous evening wakefulness. In a subsequent test phase, the speed of relearning of the discrimination task was examined as indicator of memory, whereby rats were either tested in the same context as during training or in a different context. Sleep promoted relearning of the conditional discrimination task, and this effect was similar for testing memory in the same or different context (p < 0.001). Independent of sleep and wakefulness during the retention interval, animals showed faster relearning when tested in the same context as during learning, compared with testing in a different context (p < 0.001). The benefitting effect of sleep on discrimination learning was primarily due to an enhancing effect on response suppression during the nogo stimulus. We infer from these results that sleep enhances memory for inhibitory behavioral control in a generalized context-independent manner and thereby might eventually also contribute to the abstraction of schema-like representations.

Context memory formed in medial prefrontal cortex during infancy enhances learning in adulthood.

Adult behavior is commonly thought to be shaped by early-life experience, although episodes experienced during infancy appear to be forgotten. Exposing male rats during infancy to discrete spatial experience we show that these rats in adulthood are significantly better at forming a spatial memory than control rats without such infantile experience. We moreover show that the adult rats' improved spatial memory capability is mainly based on memory for context information during the infantile experiences. Infantile spatial experience increased c-Fos activity at memory testing during adulthood in the prelimbic medial prefrontal cortex (mPFC), but not in the hippocampus. Inhibiting prelimbic mPFC at testing during adulthood abolished the enhancing effect of infantile spatial experience on learning. Adult spatial memory capability only benefitted from spatial experience occurring during the sensitive period of infancy, but not when occurring later during childhood, and when sleep followed the infantile experience. In conclusion, the infantile brain, by a sleep-dependent mechanism, favors consolidation of memory for the context in which episodes are experienced. These representations comprise mPFC regions and context-dependently facilitate learning in adulthood.

Sleep-slow oscillation-spindle coupling precedes spindle-ripple coupling during development.

STUDY OBJECTIVES: Sleep supports systems memory consolidation through the precise temporal coordination of specific oscillatory events during slow-wave sleep, i.e. the neocortical slow oscillations (SOs), thalamic spindles, and hippocampal ripples. Beneficial effects of sleep on memory are also observed in infants, although the contributing regions, especially hippocampus and frontal cortex, are immature. Here, we examined in rats the development of these oscillatory events and their coupling during early life. METHODS: EEG and hippocampal local field potentials were recorded during sleep in male rats at postnatal days (PD)26 and 32, roughly corresponding to early (1-2 years) and late (9-10 years) human childhood, and in a group of adult rats (14-18 weeks, corresponding to ~22-29 years in humans). RESULTS: SO and spindle amplitudes generally increased from PD26 to PD32. In parallel, frontocortical EEG spindles increased in density and frequency, while changes in hippocampal ripples remained nonsignificant. The proportion of SOs co-occurring with spindles also increased from PD26 to PD32. Whereas parietal cortical spindles were phase-locked to the depolarizing SO-upstate already at PD26, over frontal cortex SO-spindle phase-locking emerged not until PD32. Co-occurrence of hippocampal ripples with spindles was higher during childhood than in adult rats, but significant phase-locking of ripples to the excitable spindle troughs was observed only in adult rats. CONCLUSIONS: Results indicate a protracted development of synchronized thalamocortical processing specifically in frontocortical networks (i.e. frontal SO-spindle coupling). However, synchronization within thalamocortical networks generally precedes synchronization of thalamocortical with hippocampal processing as reflected by the delayed occurrence of spindle-ripple phase-coupling.

Sleep-dependent decorrelation of hippocampal spatial representations.

Neuronal ensembles are crucial for episodic memory and spatial mapping. Sleep, particularly non-REM (NREM), is vital for memory consolidation, as it triggers plasticity mechanisms through brain oscillations that reactivate neuronal ensembles. Here, we assessed their role in consolidating hippocampal spatial representations during sleep. We recorded hippocampus activity in rats performing a spatial object-place recognition (OPR) memory task, during encoding and retrieval periods, separated by intervening sleep. Successful OPR retrieval correlated with NREM duration, during which cortical oscillations decreased in power and density as well as neuronal spiking, suggesting global downregulation of network excitability. However, neurons encoding specific spatial locations (i.e., place cells) or objects during OPR showed stronger synchrony with brain oscillations compared to non-encoding neurons, and the stability of spatial representations decreased proportionally with NREM duration. Our findings suggest that NREM sleep may promote flexible remapping in hippocampal ensembles, potentially aiding memory consolidation and adaptation to novel spatial contexts.

Sleep-A brain-state serving systems memory consolidation.

Although long-term memory consolidation is supported by sleep, it is unclear how it differs from that during wakefulness. Our review, focusing on recent advances in the field, identifies the repeated replay of neuronal firing patterns as a basic mechanism triggering consolidation during sleep and wakefulness. During sleep, memory replay occurs during slow-wave sleep (SWS) in hippocampal assemblies together with ripples, thalamic spindles, neocortical slow oscillations, and noradrenergic activity. Here, hippocampal replay likely favors the transformation of hippocampus-dependent episodic memory into schema-like neocortical memory. REM sleep following SWS might balance local synaptic rescaling accompanying memory transformation with a sleep-dependent homeostatic process of global synaptic renormalization. Sleep-dependent memory transformation is intensified during early development despite the immaturity of the hippocampus. Overall, beyond its greater efficacy, sleep consolidation differs from wake consolidation mainly in that it is supported, rather than impaired, by spontaneous hippocampal replay activity possibly gating memory formation in neocortex.

Rearing is critical for forming spatial representations in pre-weanling rats.

Rearing, i.e., standing on the hind limbs in an upright posture, is part of a rat's innate exploratory motor program. Here, we examined in developing rats whether rearing is critical for the pup's capability to form spatial representations based on distal environmental cues. Pups (male) were tested at PD18, i.e., the first day they typically exhibit stable rearing, on a spatial habituation paradigm comprising a Familiarization session (with the pup exposed to an arena with a specific configuration of distal cues) followed, 3 h later, by a Test session where the pups were either re-exposed to the identical distal cue configuration (NoChange) or a changed configuration (DistalChange). In Experiment 1, rearing activity (rearing events, duration) decreased from Familiarization to Test in the NoChange pups but, remained elevated in the DistalChange group indicating that these pups recognized the distal novelty. Recognition of distal novelty was associated with increased c-Fos expression in hippocampal and medial prefrontal cortex (mPFC) areas, compared with NoChange pups. Analysis of GAD67+ cells suggested a parallel increase in excitation and inhibition specifically in prelimbic mPFC networks in response to distal cue changes. In Experiment 2, the pups were mechanically prevented from rearing while still seeing the distal cues during Familiarization. Rearing activity in the Test session of these pups did not differ between groups that were or were not exposed to a changed distal cue configuration at Test. The findings evidence a critical role of rearing for the emergence of allocentric representations integrating distal space during early development.

An evolutionary conserved division-of-labor between archicortical and neocortical ripples organizes information transfer during sleep.

Systems-level memory consolidation during sleep depends on the temporally precise interplay between cardinal sleep oscillations. Specifically, hippocampal ripples constitute a key substrate of the hippocampal-neocortical dialog underlying memory formation. Recently, it became evident that ripples are not unique to archicortex, but constitute a wide-spread neocortical phenomenon. To date, little is known about the morphological similarities between archi- and neocortical ripples. Moreover, it remains undetermined if neocortical ripples fulfill distinct functional roles. Leveraging intracranial recordings from the human medial temporal lobe (MTL) and neocortex during sleep, our results reveal region-specific functional specializations, albeit a near-uniform morphology. While MTL ripples synchronize the memory network to trigger directional MTL-to-neocortical information flow, neocortical ripples reduce information flow to minimize interference. At the population level, MTL ripples confined population dynamics to a low-dimensional subspace, while neocortical ripples diversified the population response; thus, constituting an effective mechanism to functionally uncouple the MTL-neocortical network. Critically, we replicated the key findings in rodents, where the same division-of-labor between archi- and neocortical ripples was evident. In sum, these results uncover an evolutionary preserved mechanism where the precisely coordinated interplay between MTL and neocortical ripples temporally segregates MTL information transfer from subsequent neocortical processing during sleep.

Sleep enhances memory consolidation in the hippocampus-dependent object-place recognition task in rats.

The positive impact of sleep on memory consolidation has been shown for human subjects in numerous studies, but there is still sparse knowledge on this topic in rats, one of the most prominent model species in neuroscience research. Here, we examined the role of sleep in the object-place recognition task, a task closely comparable to tasks typically applied for testing human declarative memory: It is a one-trial task, hippocampus-dependent, not stressful and can be repeated within the same animal. A test session consisted of the Sample trial, followed by a 2-h retention interval and a Test trial, the latter examining the memory the rat had for the places of two objects presented at the Sample trial. In Experiment 1, each rat was tested twice, with the retention interval taking place either in the morning or evening, i.e., in the inactive or active phase, respectively. Rats showed significantly (p<0.01) better memory for object place after the Morning session. To control for confounding circadian factors, in Experiment 2 rats were tested four times, i.e., in the morning or in the evening while sleep was or was not deprived. Sleep during the retention interval was recorded polysomnographically. Rats only showed significant memory for the target object place in the Test trial after the Morning retention interval in the absence of sleep deprivation, and recognition performance in this condition was significantly superior to that in the three other conditions (p<0.05). EEG recordings during spontaneous morning sleep revealed increased slow oscillation (0.85-2.0 Hz) and upper delta (2.0-4.0 Hz), but reduced spindle band (10.5-13.5 Hz) activity, as compared to evening sleep. However, spindle band power was increased in the Morning retention interval in comparison to a Morning Baseline period (p<0.05). We conclude that consolidation of object-place memory depends on sleep, and presumably requires NonREM sleep rich in both slow wave and spindle activity.