Biology subjects

Born, J.

Publications and source records attributed to Born, J..

At least 19 recordsLinked to original sources

bioRxiv2026

The role of sleep in the retention and long-term maintenance of newly formed ability self-beliefs

Sleep supports the consolidation of newly acquired information, however its role in the formation of self-beliefs has not yet been examined. Here, we investigated whether sleep facilitates the retention, stabilization, revision and long-term maintenance of newly formed ability beliefs. Using a Sleep vs. Wake between-subjects design (N=54), participants completed the Learning Of Own Performance (LOOP) task, which allowed them to form new positive and negative ability self-beliefs based on mocked feedback at a first session, and to revise them when encountering contradictory feedback at a second session. Belief formation was followed by either a sleep or wake retention interval. Belief states were tested at four time points: immediately after belief formation, after the 12-h retention interval, following the revision phase and after three weeks. Participants successfully formed and revised self-beliefs using the LOOP task. Compared with wakefulness, sleep following belief formation did not affect belief retention across the 12-h interval, nor did it stabilize beliefs against their revision. However, after three weeks, participants who slept after belief formation showed a shift towards more positivity for the initially formed low ability self-beliefs. Contrary to our hypotheses, sleep did not enhance short-term retention or stabilization of newly formed self-beliefs. However, the more positively recalled ability self-belief associated with the initially low-performance condition suggest that sleep may facilitate a positive long-term shift.

neuroscience↗

bioRxiv2026

Hunger and sleep recruit distinct brain systems to form spatial memory

By demonstrating that hunger consolidates spatial memory via a non-hippocampal mechanism that critically involves the retrosplenial cortex, we identify a mode of memory formation that is distinct from well-known hippocampus-dependent memory formation during sleep. Food-deprived rats encoded object locations and, during a subsequent 2-h consolidation phase, either received food and slept (Sleep-Fed) or stayed awake (Wake-Fed), or remained hungry and stayed awake (Wake-Hungry). At later retrieval testing, both Wake-Hungry and Sleep-Fed rats exhibited robust spatial memory, whereas Wake-Fed rats did not. Blocking neuropeptide-Y (NPY) signaling during the consolidation phase abolished hunger-consolidated memory. Unlike sleep-dependent consolidation, hunger-consolidated memory did not require the hippocampus during consolidation or retrieval, and not even during encoding. In contrast, inhibiting retrosplenial cortex during retrieval abolished hunger-consolidated memory but spared memory formed during sleep. Thus, recruitment of brain systems to form spatial memory is tuned to specific brain states, and fundamentally differs between sleep and hunger.

neuroscience↗

bioRxiv2026

Prefrontal control of hippocampal map reorganization during sleep

During wakefulness, exposure to novel experiences induces hippocampal remapping, in which place cell ensembles reorganize to form distinct representations of new information. Classical models of systems consolidation posit that subsequent sleep stabilizes these wake-formed representations and supports their gradual transfer to medial prefrontal cortex (mPFC) networks primarily via bottom-up hippocampal reactivations. Using miniscope Ca2+ imaging of CA1 place cells, we monitored hippocampal activity as mice explored a familiar environment followed by a similar novel one. As expected, place cells remapped in the novel context. However, a single episode of post-encoding sleep selectively reversed remapping dynamics by promoting the reinstatement of familiar place cell representations in the novel environment, an effect that was absent in the wake condition. This neural reinstatement was accompanied by behavioral indicators of familiarity, including reduced exploration and rearing. Chemogenetic inactivation of the mPFC during post-encoding sleep abolished this generalization effect, and instead preserved the novel hippocampal map. Thus, our results extend current models by showing that sleep not only consolidates wake-established hippocampal patterns, but actively shapes hippocampal maps via prefrontal control, thereby supporting memory generalization.

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bioRxiv2026

Juvenile rat's sleep enables schema memory across episodes before expression of memory for individual episodes

Schema memory refers to generalized knowledge extracted from multiple related episodes. According to systems consolidation theory, such representations emerge during sleep through the transformation of hippocampus-dependent episodic memories into neocortical schema representations. Whether this process requires mature episodic memory expression during early development remains unclear. Here, we examined schema formation in infant rats with an immature hippocampus. At postnatal day (PD) 25, pups (n=24) were tested in an adapted object-place paradigm enabling abstraction of a spatial regularity across eight consecutive episodes. Following encoding, pups either slept or remained awake for two hours, and schema memory was tested 22 hours later. Control groups were exposed to pseudorandomized object configurations. Schema memory was expressed only after exposure to spatial regularities and only when sleep followed encoding. To directly assess episodic memory under comparable conditions, an additional group of pups (n=12) was tested in a standard single-episode object-place recognition (OPR) task with post-encoding sleep. At a 4-hours test, these pups did not show episodic object-place memory. These findings indicate that sleep supports schema memory formation during early life under conditions in which the expression of robust single-episode memory is not yet evident, suggesting that schema abstraction in infancy does not depend on fully developed hippocampal episodic representations.

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bioRxiv2026

Natural sleep, but not propofol-induced anesthesia preserves spatial and procedural memory consolidation

Propofol-induced general anesthesia and natural sleep are both associated with GABA-A-ergic inhibition and slow-wave activity. Whereas sleep actively supports memory consolidation, consolidation may be disrupted during anesthesia. Here, we compared EEG and memory data from 19 participants undergoing surgery under propofol-induced anesthesia with data from 17 participants taking a nap. In both groups, participants completed a hippocampus-dependent spatial memory task (Virtual Water Maze) and a procedural memory task (Mirror Tracing) before (pre) and after (post) an interval filled with either anesthesia or sleep. Performance declined from pre to post in the propofol group for both tasks, whereas it remained stable in the sleep group. Slow oscillations (SO) occurred during both non-REM sleep and propofol-induced anesthesia. However, only during non-REM sleep did SOs show increased spindle activity during the SO upstate. Together, these findings suggest that propofol anesthesia disrupts memory consolidation, most likely because SOs under anesthesia lack the spindle coupling that mediates the hippocampal-neocortical information transfer underlying systems memory consolidation.

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bioRxiv2026

Hippocampal CA1 neurons are crucial for sleep-associated memory formation in humans: The role of theta power during NREM sleep

The formation of long-term memory during sleep depends on the reactivation and redistribution of recently acquired mnemonic information during non-rapid eye movement (NREM) sleep. Animal studies suggest that hippocampal memory replay during slow-wave sleep is coordinated through the interaction of sharp-wave ripples, thalamocortical sleep spindles, and neocortical slow oscillations (SOs). However, direct evidence for the contribution of hippocampal network dynamics to sleep-dependent memory consolidation in humans remains limited. Here, we investigated sleep-dependent memory consolidation in patients (n=13) with transient global amnesia (TGA), a clinical syndrome associated with focal and transient lesions of the hippocampal CA1 region. Patients completed a verbal paired-associative learning task followed by nocturnal polysomnography and subsequent memory retrieval during the acute phase of TGA (acute condition) and again after clinical recovery (follow-up condition). Overnight memory consolidation was significantly impaired during the acute phase compared with the follow-up session. NREM EEG theta power (4-8 Hz) was reduced during the acute phase of TGA. Importantly, increases in theta power from the acute to the follow-up session predicted corresponding improvements in memory consolidation within individuals. In contrast, established NREM markers of sleep-dependent memory consolidation, including sleep spindle density, SO density, and SO-spindle coupling, did not differ between the acute and follow-up conditions. These findings suggest that transient hippocampal CA1 dysfunction disrupts sleep-related hippocampal network dynamics reflected in reduced NREM theta activity, which in turn is associated with impaired memory consolidation. Sleep-related theta oscillations may therefore represent a functional marker of hippocampal network integrity during sleep-dependent memory consolidation in humans.

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bioRxiv2026

From co-occurrence to increasingly precise temporal coordination: Development of slow oscillation-spindle coupling from infancy to toddlerhood

The precise temporal coordination of sleep spindles and slow oscillations (SOs) is a key mechanism of memory consolidation during sleep, yet little is known about its emergence early in life. Here, we investigated the development of SO-spindle coupling in 9- to 16-month-old infants and toddlers. While morphologies of spindles and SOs were largely comparable between infants younger than one year and toddlers older than one year, their temporal coordination showed clear age-related changes. In infants, SO-spindle co-occurrence was highest over occipital cortex regions, as was to be expected by chance based on the spatial distribution of the two oscillations. Co-occurrence rates in infants already exceeded chance level, but only at central regions where the highest co-occurrence rates were observed in toddlers. Moreover, a nesting of spindles into the upstate of SOs was evident in fronto-central regions even in infants, and increased in strength and precision with age. Together, these findings suggest that coordinated SO-spindle coupling emerges in the second half of the first year of life and becomes increasingly precise across the transition into toddlerhood.

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bioRxiv2026

Post-encoding slow-wave amplitude during a daytime nap predicts pattern completion from sparse visual cues

Pattern completion refers to the reinstatement of a stored memory representation from partial or degraded cues. In this sense, it enables a form of cue-based generalization: the same memory representation can be retrieved across different, incomplete versions of the original input. Sleep supports hippocampus-dependent memory consolidation and may facilitate such flexible retrieval, but it remains unclear whether post-encoding sleep improves visual pattern completion from degraded cues. Previous sleep studies have mainly examined mnemonic discrimination or relational memory, leaving open whether sleep directly enhances the recovery of learned visual scenes from sparse perceptual information. We tested this question using the Memory Image Completion (MIC) task in a polysomnographic within-subject sleep-wake design. Twenty-eight healthy young adults (14 female; mean age 23.4 {+/-} 3.1 years) encoded scene-label associations and were tested immediately and after either a 90-min daytime nap or a matched wake interval. During retrieval, learned and new scenes were presented at five levels of visual completeness. A separate pre-encoding baseline nap assessed individual sleep physiology without prior learning. Sleep did not generally improve performance across all retrieval conditions. Instead, it selectively enhanced consolidation of learned scenes when visual cues were maximally degraded (p = .001) indicating increased pattern completion. No corresponding sleep effect was found for new scenes (all p > .31), suggesting that the benefit was specific to the recovery of previously encoded scene representations. Slow-wave amplitude during the post-encoding nap predicted consolidation of learned scenes under the most degraded condition (p = .011; FDR-corrected p = .042), whereas baseline slow-wave amplitude did not (p > .11). These findings suggest that post-encoding sleep facilitates cue-based recovery of learned visual representations from strongly degraded input, and that this benefit is linked to slow-wave amplitude during post-encoding sleep. Together, these results link sleep-dependent consolidation to visual pattern-completion-like retrieval and extend previous work on sleep-related memory transformation from verbal and relational paradigms to the recovery of learned scene representations from degraded cues.

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bioRxiv2026

Sleep forms flexible context representations in toddlers

Sleep consolidates episodic memory through a hippocampus-dependent process in adults. Whether and how sleep supports memory consolidation during early life, when hippocampal function is immature, remains unclear. Here, we examined effects of sleep on the consolidation of spatial context, a core component of episodic memory, in toddlers aged 2 -3 years. Toddlers were familiarized with two spatial contexts, followed by a [~]90-min nap or an equivalent wake period. Afterwards, with a hide-and-seek game we tested their ability to relocate toys within these contexts. Only after post-familiarization sleep, the toddlers showed significant context memory and formed stronger associations between toys and specific contexts compared to wakefulness. Contextual memory was positively correlated with spindle density and slow oscillation-spindle phase-amplitude coupling during non-rapid eye movement (NonREM) sleep. Despite hippocampal immaturity, the sleeping toddlers brain seems to engage consolidation processes similar to those in adults to form spatial context memory for the flexible use in novel situations.

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bioRxiv2026

Sleep enhances spatial schema memory formation in humans

Schema memory, a generalized representation formed across episodes sharing regularities, is thought to arise through sleep-dependent systems consolidation. Yet, direct evidence in humans remains sparse. Here, sixty young adults navigated a virtual-reality arena and learned a spatial distribution of object-category ratios across five sessions (toys vs. household items, hidden in boxes at different locations). Participants then either slept or were sleep-deprived for a full night, followed by two recovery nights before memory testing, or they were tested after a short 30-min delay spent awake. Only after a three-day delay did spatial memory of old box locations predict spatial interpolation to new box locations, indicating time-dependent schema expression. Critically, sleep distinctly enhanced spatial integration beyond the effect of time. This benefit was predicted by frontal cortical slow oscillation-spindle coupling during the first post-encoding night, thus linking sleep oscillations to the transformation of episodic spatial memories into integrated schema representations.

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bioRxiv2026

Hippocampus consolidates memory in the upstate of cortical sleep slow oscillations

Cortical slow oscillations (SOs), a hallmark of non-rapid eye movement (NonREM) sleep, have been proposed to support systems memory consolidation by organizing hippocampal-cortical communication. However, whether consolidation requires hippocampal memory processing during SO-defined windows is unclear. Here, we used closed-loop optogenetics to transiently inhibit dorsal hippocampal activity in adult rats (N = 12) during NonREM sleep following object-place association learning, either during cortical SO upstates or outside SOs, compared with a no-stimulation control. Inhibition during SO upstates completely abolished expression of memory at retrieval, despite preserved sleep architecture and intact cortical SO and spindle dynamics. By contrast, inhibition outside SOs preserved memory and only slightly reduced performance compared to the no-stimulation control. Memory impairment from hippocampal inhibition was largely mediated by SO upstates nesting spindles. Our findings provide novel evidence that sleep-dependent systems consolidation requires precisely timed hippocampal-neocortical dialogue.

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bioRxiv2025

Wake consolidates event memory, sleep binds it with context

Sleep is thought to be superior to wakefulness in consolidating memory, due to a hippocampus-driven process enhancing the contextual integration of events. We compared recall of associative memory in different contexts, and found that memory is also consolidated during wakefulness, although in a qualitatively distinct way. Healthy participants performed a cued stimulus-response (S-R) learning task requiring speeded object classification. Learning was followed by 2 hours of sleep or wakefulness. Reaction times revealed stronger S-R memory after sleep than wakefulness with retrieval in the same context, and this benefit was linked to increased sleep spindle activity. In contrast, S-R memory was stronger after wakefulness than sleep when tested in a different context. This wake-dependent enhancement had a fast onset and was reversed by delayed sleep. We conclude that, unlike sleep strengthening the binding of an event with its context, wakefulness stabilizes event representations itself, i.e., not bound to a specific context.

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bioRxiv2024

Modeling CAR Response at the Single-Cell Level Using Conditional Optimal Transport

Chimeric Antigen Receptor (CAR) T cell therapy is a promising area of cancer immunotherapy. However, many challenges such as loss of persistence, T cell exhaustion, and therapy associated toxicities hamper further advancement of CAR T cell therapy. Therefore, recent efforts have focused on designing improved CARs that show better therapeutic characteristics. However, it is unfeasible to test all CAR variants in lab-based assays as CARs consist of multiple intracellular signalling domains. This results in over 100000 possible variants. We leverage computational modeling to navigate this vast combinatorial space by learning the relationship between CAR design and T cell functionality, thereby proposing promising CAR T cell designs. CAR T cells expressing different variants can be viewed as cells that underwent different perturbations. Neural Optimal Transport is an upcoming field that can model single cell perturbations and predict unseen cells and conditions. In this work we leverage the conditional Monge Gap to model the response to CAR expression at a single-cell level and generate gene expression of cells that express an unseen CAR design. We show that CAR OT (CAROT) significantly outperforms the baseline for gene expression prediction for in-distribution CAR variants, with distinct gene expression patterns per CAR that capture biological characteristics. When predicting unseen CAR variants, we demonstrate promising results in terms of gene expression prediction and show the model learns gene expression patterns linked to domains in the training set. This work demonstrates that optimal transport may support discovery and development of new CAR T cell designs.

synthetic biology↗

bioRxiv2024

Spatiotemporal patterns of theta-band activity during rapid-eye movement sleep: a magnetoencephalography analysis

Theta oscillations (4-8 Hz) in frontal cortical regions are present to different degrees across states of consciousness. In sleep, theta is prominent in periods of rapid eye-movement (REM) sleep. Theta has been linked to processes of memory consolidation; however, its mechanistic contribution specifically during REM sleep is not well understood. Interestingly, in the wake state, frontal theta activity increases during effortful cognitive tasks involving executive functions such as working memory, hinting at similarities in circuitry, and potentially, function. The aim of the present work is to create a spatially resolved, whole-brain characterisation of REM oscillatory activity in healthy human subjects, distinguishing theta from neighbouring frequency bands, differentiating substages of REM sleep (phasic and tonic REM), and comparing REM theta to that which is evoked during a working memory task. To that end, we analysed magneto- and electroencephalography (M/EEG) data recorded during overnight sleep in 10 healthy subjects, and similar data from 17 healthy subjects who performed a working memory task, using a novel whole-brain, source-localised MEG approach. Our results show that (i) theta activity has a frontal midline topography that is distinct from those of other prominent frequency bands in REM (delta, alpha, beta), (ii) theta activity in frontal midline regions is best observed within a focused 5-7 Hz range, separating it from occipital alpha activity, (iii) REM theta is dominant over the frontal midline but is also observed in several sub-cortical areas, (iv) theta is more widespread in tonic than phasic REM sleep, and (v) the focused frontal midline theta pattern observed in REM phasic sleep is the most similar of all observed sleep substages to theta evoked by a working memory task. These results enhance our understanding of theta physiology in REM sleep and suggest future targets for research into REMs role in learning and memory.

neuroscience↗

bioRxiv2023

Targeted memory reactivation is not more effective during slow wave sleep than sleep stage 2

Sleep facilitates memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.

neuroscience↗

bioRxiv2023

Neural signatures of declarative memory cueing using odors during sleep

Long-term memories are formed by repeated reactivation of newly encoded information during sleep. This process can be enhanced by using memory-associated reminder cues like sounds and odors. While auditory cueing has been researched extensively, few electrophysiological studies have exploited the various benefits of olfactory cueing. We used high-density electroencephalography in an odor-cueing paradigm that was designed to isolate the neural responses specific to the cueing of declarative memories. We show widespread cueing-induced increases in the duration and rate of sleep spindles. Higher spindle rates were most prominent over centro-parietal areas and largely overlapping with a concurrent increase in the amplitude of slow oscillations (SOs). Interestingly, greater SO amplitudes were linked to a higher likelihood of coupling a spindle and coupled spindles expressed during cueing were more numerous in particular around SO up states. We thus identify temporally and spatially coordinated enhancements to sleep spindles and slow oscillations as a candidate mechanism behind the benefits of odor cueing. Our results further demonstrate the feasibility of studying neural activity patterns related to memory processing using olfactory cueing during sleep. Statement of SignificanceMemory cueing during sleep allows insights into memory consolidation. This study is the first to investigate olfactory cueing-induced declarative memory processing using high-density EEG, while robustly controlling for critical confounding factors. The use of odors as cues, instead of more common auditory stimuli, further minimizes possible distortions due to sensory-evoked potentials. We demonstrate intricate changes in brain activity in response to cueing, such as the patterns of sleep spindles, slow oscillations, and their spatiotemporal coupling. We provide evidence that the enhancement of slow oscillation amplitudes, together with associated increases in sleep spindle rates, could be the key mechanism behind cueing-related memory benefits. We moreover show that prior findings obtained using auditory cueing are not the mere result of tone-evoked responses but might be genuine signatures of memory processing.

neuroscience↗

bioRxiv2020

Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

BackgroundSleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of NonREM sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory. AimsInvestigate the role of metabotropic glutamate receptor 5 (mGluR5) on memory processing during sleep. MethodsIn two placebo-controlled within-subject cross-over experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested in the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II, participants learned new word-pairs in the morning after sleep. Results/OutcomesSurprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memoryrelevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in REM sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under Fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Conclusions/InterpretationsOur findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations. Declaration of interest/FundingThe authors have nothing to disclose and funders had no influence on the research presented here.

neuroscience↗

bioRxiv2020

Vast amounts of encoded items nullify but do not reverse the effect of sleep on declarative memory

Sleep strengthens memories by repeatedly reactivating associated neuron ensembles. Our studies show that although long-term memory for a medium number of word-pairs (160) benefits from sleep, a large number (320) does not. This suggest an upper limit to the amount of information that has access to sleep-dependent declarative memory consolidation, which is possibly linked to the availability of reactivation opportunities. Due to competing processes of global forgetting that are active during sleep, we hypothesised that even larger amounts of information would enhance the proportion of information that is actively forgotten during sleep. In the present study, we aimed to induce such forgetting by challenging the sleeping brain with vast amounts of to be remembered information. For this, 80 participants learned a very large number of 640 word-pairs over the course of an entire day and then either slept or stayed awake during the night. Recall was tested after another night of regular sleep. Results revealed comparable retention rates between the sleep and wake groups. Although this null-effect can be reconciled the concept of limited capacities available for sleep-dependent consolidation, it contradicts our hypothesis that sleep would increase forgetting compared to the wake group. Additional exploratory analyses relying on equivalence testing and Bayesian statistics reveal that there is evidence against sleep having a detrimental effect on the retention of declarative memory at high information loads. We argue that forgetting occurs in both wake and sleep states through different mechanisms, i.e., through increased interference and through global synaptic downscaling, respectively. Both of these processes might scale similarly with information load.

neuroscience↗