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-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.

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.

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-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.

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.

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.

Cortico-Hippocampal Oscillations Are Associated With the Developmental Onset of Hippocampal-Dependent Memory.

Hippocampal-dependent memories emerge late during postnatal development, aligning with hippocampal maturation. During sleep, the two-stage memory formation model states that through hippocampal-neocortical interactions, cortical slow-oscillations (SO), thalamocortical Spindles, and hippocampal sharp-wave ripples (SWR) are synchronized, allowing for the consolidation of hippocampal-dependent memories. However, evidence supporting this hypothesis during development is still lacking. Therefore, we performed successive object-in-place tests during a window of memory emergence and recorded in vivo the occurrence of SO, Spindles, and SWR during sleep, immediately after the memory encoding stage of the task. We found that hippocampal-dependent memory emerges at the end of the 4th postnatal week independently of task overtraining. Furthermore, we observed that those animals with better performance in the memory task had increased Spindle density and duration and lower density of SWR. Moreover, we observed changes in the SO-Spindle and Spindle-SWR temporal-coupling during this developmental period. Our results provide new evidence for the onset of hippocampal-dependent memory and its relationship to the oscillatory phenomenon occurring during sleep that helps us understand how memory consolidation models fit into the early stages of postnatal development.

Effects of Information Load on Schema and Episodic Memory Formation.

The formation of semantic memories is assumed to result from the abstraction of general, schema-like knowledge across multiple experiences, while at the same time, episodic details from individual experiences are forgotten. Against this backdrop, our study examined the effects of information load (high vs. low) during encoding on the formation of episodic and schema memory using an elaborated version of an object-place recognition (OPR) task in rats. The task allowed for the abstraction of a spatial rule across four (low information load) or eight (high information load) encoding episodes (spaced apart by a 20 min interval) in which the rats could freely explore two objects in an open field arena. After this encoding phase, animals were left undisturbed for 24 h and then tested either for the expression of schema memory, i.e., for the spatial rule, or memory for an individual encoding episode. Rats in the high information load condition exhibited a more robust schema memory for the spatial rule than in the low information load condition. In contrast, rats in the low load condition showed more robust memory for individual learning episodes than in the high information load condition. Our findings of opposing effects might point to an information-load-dependent competitive relationship between processes of schema and episodic memory formation, although other explanations are possible.

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.

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.

The expression of allocentric object-place recognition memory during development.

The allocentric representation of space is a fundamental pillar of episodic experience. In infant rats, the neural circuitry underlying the formation of allocentric spatial representations is functioning from early on when eyes are opening, i.e., before postnatal day (PD) 15. However, it remains unclear when and how during early development rats use these representations to regulate spatial behavior. Here, we studied indicators of memory-based spatial navigation using a classical object-place recognition (OPR) task set-up in infant (PD15), pre-weanling (PD18), juvenile (PD25), peri-adolescent (PD31), adolescent (PD38, PD48), and young adult rats (PD84). On the task, rats explored an arena with two identical objects, and memory was tested in a recall phase 3 h later in the same arena with, one object displaced from its original location. Only at adolescence (PD38), rats showed the typical adult-like expression of allocentric spatial memory with a preferential exploration of the object at the novel location. However, the first expression of allocentric spatial memory was revealed already in PD18 rats, which contrasting with PD84 rats, showed a preference to explore the object at the familiar location. At PD31, rats showed a null preference between the object-locations. Nevertheless, spatial memory at this age expressed in a preference for the zone including the familiar object-location. In PD15 rats, we found no evidence for a memory-based organization of spatial behavior. In conclusion, although rats might be able to form allocentric neuronal representations of space already earlier, only from PD18 on, such representations are used to organize spatial behavior, with a motivational shift from familiarity to novelty-driven navigation occurring during adolescence.

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.

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.

Sleep stage dynamics in neocortex and hippocampus.

Mammalian sleep comprises the stages of slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Additionally, a transition state is often discriminated which in rodents is termed intermediate stage (IS). Although these sleep stages are thought of as unitary phenomena affecting the whole brain in a congruent fashion, recent findings have suggested that sleep stages can also appear locally restricted to specific networks and regions. Here, we compared in rats sleep stages and their transitions between neocortex and hippocampus. We simultaneously recorded the electroencephalogram (EEG) from skull electrodes over frontal and parietal cortex and the local field potential (LFP) from the medial prefrontal cortex and dorsal hippocampus. Results indicate a high congruence in the occurrence of sleep and SWS (>96.5%) at the different recording sites. Congruence was lower for REM sleep (>87%) and lowest for IS (<36.5%). Incongruences occurring at sleep stage transitions were most pronounced for REM sleep which in 36.6 per cent of all epochs started earlier in hippocampal LFP recordings than in the other recordings, with an average interval of 17.2 ± 1.1 s between REM onset in the hippocampal LFP and the parietal EEG (p < 0.001). Earlier REM onset in the hippocampus was paralleled by a decrease in muscle tone, another hallmark of REM sleep. These findings indicate a region-specific regulation of REM sleep which has clear implications not only for our understanding of the organization of sleep, but possibly also for the functions, e.g. in memory formation, that have been associated with REM sleep.

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.

Post-Learning Sleep Transiently Boosts Context Specific Operant Extinction Memory.

Operant extinction is learning to supress a previously rewarded behavior. It is known to be strongly associated with the specific context in which it was acquired, which limits the therapeutic use of operant extinction in behavioral treatments, e.g., of addiction. We examined whether sleep influences contextual memory of operant extinction over time, using two different recall tests (Recent and Remote). Rats were trained in an operant conditioning task (lever press) in context A, then underwent extinction training in context B, followed by a 3-h retention period that contained either spontaneous morning sleep, morning sleep deprivation, or spontaneous evening wakefulness. A recall test was performed either immediately after the 3-h experimental retention period (Recent recall) or after 48 h (Remote), in the extinction context B and in a novel context C. The two main findings were: (i) at the Recent recall test, sleep in comparison with sleep deprivation and spontaneous wakefulness enhanced extinction memory but, only in the extinction context B; (ii) at the Remote recall, extinction performance after sleep was enhanced in both contexts B and C to an extent comparable to levels at Recent recall in context B. Interestingly, extinction performance at Remote recall was also improved in the sleep deprivation groups in both contexts, with no difference to performance in the sleep group. Our results suggest that 3 h of post-learning sleep transiently facilitate the context specificity of operant extinction at a Recent recall. However, the improvement and contextual generalization of operant extinction memory observed in the long-term, i.e., after 48 h, does not require immediate post-learning sleep.