Sleep deprivation and memory: A neurobiological perspective

Emotional Reactivity in Posttraumatic Stress Disorder:Behavioural and Neurobiological Correlates of Underlying Mechanisms and the Role of Emotional Memory Modification

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessAcute Sleep Deprivation May Reduce Impact of Traumatic MemoriesNick ZagorskiNick ZagorskiPublished Online:1 Sep 2015https://doi.org/10.1176/appi.pn.2015.8a22AbstractHolding off on sleep on the first night after watching a traumatic film reduced the frequency of subsequent "flashbacks" over the following week.Over time, a lack of sleep can lead to a host of cognitive and mood problems. Yet, in acute settings, sleep deprivation has been shown to provide some benefit to the brain. One of the most studied phenomena in sleep deprivation research is its potential to rapidly cure depressive symptoms—at least until the person falls asleep.Marcos Mesa Sam Wordley/ShutterstockNow, research appearing in the journal Sleep has demonstrated that one night of sleep deprivation reduces the impact and intrusiveness of emotional memories, the type that arise from watching or experiencing a traumatic event."It may seem counterintuitive, given that people who experience trauma often have difficulty falling asleep to begin with," said study author Kate Porcheret, Ph.D., a research scientist at the Nuffield Department of Clinical Neurosciences at the University of Oxford. "But we think that forgoing sleep right after a trauma interferes with the consolidation of these emotional memories and prevents them from becoming intrusive." Porcheret noted that the exact process by which these memories are formed is still being researched, but the general belief in the field is that emotional memories are likely distinct from typical conscious recollection, with processing that relies more on the emotional situation surrounding an event rather than the context of that event. Delaying memory consolidation by sleep deprivation might therefore serve to distance the emotion from the context.For the current study, Porcheret and her colleagues showed 42 healthy adults a short film with traumatic content. After asking the participants to report on the immediate effect of the film, the group was split in half, with some sent home for a normal night of sleep while the others went to a sleep lab where they underwent total sleep deprivation. Video Gaming May Also Help to Reduce Intrusive MemoriesWhile sleep deprivation may help prevent emotional memories from forming, what happens if someone has already formed that traumatic memory? A study published in the July issue of Psychological Science suggests that videogames—the puzzle game Tetris specifically—may be able to help. Researchers at the University of Oxford and the Medical Research Council Cognition and Brain Sciences Unit at Cambridge University found that engaging in this visuospatial task could also reduce the frequency of intrusive memories. In this case, though, the visuospatial task works to disturb the process of reconsolidation—the time when a memory comes to the surface following a trigger—by competing for the brain's visual memory.A total of 51 adult volunteers watched the same trauma video as the participants in Porcheret's study watched. After 24 hours, the participants returned to the lab, where half performed some filler tasks while the other half were shown some still images from the traumatic film to trigger memories and then played Tetris for 12 minutes. Over the next week, the game players reported fewer intrusive memories than their counterparts. A follow-up test confirmed that both elements—the memory reactivation with photos and the Tetris playing—were required to diminish these emotional memories."Computer Game Play Reduces Intrusive Memories of Experimental Trauma via Reconsolidation-Update Mechanisms" can be accessed here.The next morning, each person was asked to provide their thoughts on the film and then over the next six days they kept a diary in which they were asked to record any intrusive memories that popped into their heads. The researchers found that compared with the participants who had a good night's sleep, sleep-deprived participants reported the film to be less disturbing and over the course of the week registered fewer intrusive flashbacks to the film (average of 2.28 versus 3.76 flashbacks). Though this study only followed the participants for a week, Porcheret noted that other work has suggested that disrupting the initial memory formation can reduce intrusiveness for up to four years. "Now, these conditions are far removed from an actual traumatic experience, and our aim is not to induce trauma in people, but we think this type of experiment is on the same spectrum in that it creates an environment where intrusive memories can be formed," Porcheret told Psychiatric News. "So this should serve as a reasonable analogue to real-life traumatic events."She did caution that there is still much that needs to be understood about sleep and memory formation before trying to use sleep deprivation as an aid to people who experience pathological intrusive memories, such as those with posttraumatic stress disorder (PTSD) or complicated grief. This study was supported by a Wellcome Trust Strategic Award to the Sleep and Circadian Neuroscience Institute at the University of Oxford, with additional support from the Medical Research Council and a Wellcome Trust Clinical Fellowship. ■An abstract of "Psychological Effect of an Analogue Traumatic Event Reduced by Sleep Deprivation" can be accessed here. ISSUES NewArchived

068 EFFECT OF CHRONIC PHYSICAL EXERCISE ON ANXIETY IN PATIENTS WITH CHRONIC PRIMARY INSOMNIA

<p dir="ltr">The ability of the brain to rewire itself is central to its functioning. This plasticity must be tightly regulated to ensure the stability of memories and maintain normal levels of signalling. This thesis investigates two different systems contributing to the regulation of structural plasticity.</p><p dir="ltr">Nogo receptor 1 (NgR1) is a potent negative regulator of plasticity. First characterised in the setting of central nervous system injury, it is emerging as an important regulator of memory formation as well. Understanding how this system functions and is regulated could offer novel avenues for treatment of common and severe brain diseases.</p><p dir="ltr">In paper I we investigated how Nogo receptor 1 levels influence memory function and structural plasticity. Using transgenic mice, we found that constitutive overexpression of NgR1 impaired performance in the Morris water maze, while constitutive lack of NgR1 impaired novel object recognition. Further, overexpression of NgR1 limited the formation of dendritic spines. This paper adds to the growing evidence for a role for NgR1 in regulating memory formation and structural plasticity.</p><p dir="ltr">Given that NgR1 is strongly expressed in highly plastic brain regions, we hypothesised that there must be ways to bypass the growth inhibition of NgR1 to allow for lasting memory formation. In paper IV we find that a chemical LTP protocol induces rapid downregulation of dendritic NgR1 protein. Conversely, a chemical LTD protocol rapidly upregulates dendritic NgR1 protein. These findings suggest novel ways in which NgR1 levels are dynamically regulated to permit or inhibit memory formation.</p><p dir="ltr">Sleep is a well-conserved and costly behaviour, yet its function remains poorly understood. The synaptic homeostasis hypothesis is an influential theory that proposes that sleep serves to downscale synaptic weights, and several lines of evidence point to plastic changes in dendritic structure occurring during sleep. However, the evidence is conflicted regarding whether sleep results in a net growth or shrinkage of the dendritic tree. This is an important question to elucidate if we are to develop effective treatments for the ill effects of sleep loss.</p><p dir="ltr">In paper II we investigated how CA1 dendritic structure is affected by sleep deprivation. We measured dendritic length and dendritic spine density after 5 h sleep deprivation by gentle handling, and did not find any significant effects. In paper III we looked at the same issue but through a systematic review and meta- analysis. We included 30 studies in the meta-analysis, which were individually small and with high variability We found that current evidence does not indicate an effect on CA1 dendritic structure after 24 h or less of sleep deprivation. Chronic sleep deprivation of 72 h or longer does reduce CA1 spine density and dendritic length, but it remains unclear if this is solely due to sleep loss or to stress associated with the method of sleep deprivation.</p><p dir="ltr">Together, these studies advance our understanding of how structural plasticity is regulated.</p><h3>List of scientific papers</h3><p dir="ltr">I. Tobias E Karlsson, Gabriella Smedfors, <b>Alvin TS Brodin</b>, Elin Åberg, Anna Mattsson, Isabelle Högbeck, Katrin Wellfelt, Anna Josephson, Stefan Brené, Lars Olson. NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity. Cereb Cortex. 2016 Apr;26(4):1804-17. <a href="https://doi.org/10.1093/cercor/bhw007" rel="noreferrer" target="_blank">https://doi.org/10.1093/cercor/bhw007</a></p><p dir="ltr">II. <b>Alvin TS Brodin</b>, Sarolta Gabulya, Katrin Wellfelt, Tobias E Karlsson. Five Hours Total Sleep Deprivation Does Not Affect CA1 Dendritic Length or Spine Density. Front Synaptic Neurosci. 2022 Mar 14;14:854160. <a href="https://doi.org/10.3389/fnsyn.2022.854160" rel="noreferrer" target="_blank">https://doi.org/10.3389/fnsyn.2022.854160</a></p><p dir="ltr">III. <b>Alvin TS Brodin</b>, Franziska Liesecke, Julia Spielbauer, Tobias E Karlsson. Effects of sleep deprivation on dendritic architecture: A systematic review and meta-analysis of rodent studies. [Manuscript]</p><p dir="ltr">IV. <b>Alvin TS Brodin</b>, Julia Spielbauer, Katrin Wellfelt, Lars Olson, Tobias E Karlsson. Localisation and regulation of Nogo-66 receptor 1 during chemical long term potentiation and depression. [Manuscript]</p>

The role of sleep in regulating structural plasticity and synaptic strength: Implications for memory and cognitive function

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

The amygdala is a hub of emotional circuits involved in the regulation of cognitive and emotional behaviors and its critically involved in emotional reactivity, stress regulation, and fear memory. Growing evidence suggests that the amygdala plays a key role in the consolidation of emotional memories during sleep. Neuroimaging studies demonstrated that the amygdala is selectively and highly activated during rapid eye movement sleep (REM) and sleep deprivation induces emotional instability and dysregulation of the emotional learning process. Regulation of dendritic spines during sleep represents a morphological correlate of memory consolidation. Several studies indicate that dendritic spines are remodeled during sleep, with evidence for broad synaptic downscaling and selective synaptic upscaling in several cortical areas and the hippocampus. Currently, there is a lack of information regarding the regulation of dendritic spines in the amygdala during sleep. In the present work, we investigated the effect of 5 h of sleep deprivation on dendritic spines in the mouse amygdala. Our data demonstrate that sleep deprivation results in differential dendritic spine changes depending on both the amygdala subregions and the morphological subtypes of dendritic spines. We observed decreased density of mushroom spines in the basolateral amygdala of sleep deprived mice, together with increased neck length and decreased surface area and volume. In contrast, we observed greater densities of stubby spines in sleep deprived mice in the central amygdala, indicating that downscaling selectively occurs in this spine type. Greater neck diameters for thin spines in the lateral and basolateral nuclei of sleep deprived mice, and decreases in surface area and volume for mushroom spines in the basolateral amygdala compared to increases in the cental amygdala provide further support for spine type-selective synaptic downscaling in these areas during sleep. Our findings suggest that sleep promotes synaptic upscaling of mushroom spines in the basolateral amygdala, and downscaling of selective spine types in the lateral and central amygdala. In addition, we observed decreased density of phosphorylated cofilin immunoreactive and growth hormone immunoreactive cells in the amygdala of sleep deprived mice, providing further support for upscaling of dendritic spines during sleep. Overall, our findings point to region-and spine type-specific changes in dendritic spines during sleep in the amygdala, which may contribute to consolidation of emotional memories during sleep.

The intricate role of sleep in sustaining critical physiological functions and preserving cognitive integrity is well-established. Inadequate sleep, whether in duration or quality, profoundly impairs fundamental cognitive functions, including memory consolidation, sustained attention, executive decision-making, and temporal perception. This study endeavors to explore the effects of short-term sleep restriction on subjective time perception employing both retrospective and prospective paradigms to unveil how acute sleep restriction reshapes temporal cognition in healthy adults. Following ethical approval, 31 healthy volunteers aged between 18 and 35 years participated. The experimental protocol which included assessments conducted under two conditions: after four consecutive nights of regular sleep and following three nights of sleep restriction, during which participants’ sleep duration was reduced by two hours per night. Subjective time perception was evaluated using both retrospective and prospective time generation tasks (RTP and PTP). To assess cognitive performance, participants completed the Stroop test, which measures selective attention and cognitive flexibility, and the Wechsler Memory Scale-III (WMS-III), a validated instrument for evaluating short-term and working memory functions. The RTP after sleep restriction showed a significant prolongation compared to regular sleep duration (20.2 ± 8.8 vs 26.6 ± 12.3 sec, respectively; ANOVA p < 0.001). Short-term and working memory performances decreased after sleep restriction (10.8 ± 1.9 vs 10.0 ± 2.1 sec and 12.3 ± 2.1 vs 11.4 ± 2.3 sec respectively; ANOVA p ≤ 0.001 for both). Even moderate sleep restriction (e.g. a two-hour reduction) disrupts temporal cognition and memory, underscoring the critical need for sufficient sleep to sustain optimal cognitive performance in high-demand scenarios.

Sleep deprivation (SD) impairs long-term memory, but the molecular mechanisms underlying the impact of sleep loss on memory are poorly understood. Molecular changes driven by SD have thus far focused on transcription and translation. Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, have recently been recognized as an important player in memory research. However, it remains unclear how sleep deprivation modulates the expression of lncRNAs or their targets to lead to memory impairment. In this study, we explored the role of lncRNAs in the disruption of spatial memory caused by SD. We examined a set of synapse-associated lncRNAs that were identified through a transcriptome analysis after SD. Among them, we discovered that the lncRNA Cerox1 is downregulated in dorsal hippocampus following SD, and its levels recover after 2.5 hours of rebound sleep. Sleep is critical for the regulation of metabolism and sleep loss impairs mitochondrial function. Both sleep deprivation and Cerox1 knockdown were found to reduce complex I activity of the mitochondrial electron transport chain. This reduction of complex I activity is linked to the decrease in expression of a subset of complex I subunits including Ndufs1, Ndufs3, Ndufa3 and Ndufs6. Overexpression of Cerox1 has the opposite effect, leading to increased complex I activity. Sleep deprivation reduced ATP levels in the dorsal hippocampus, while Cerox1 overexpression restored it. SD disrupted memory consolidation, and this impairment was rescued when Cerox1 was overexpressed. Cerox1 transcript contains multiple miRNA binding sites that regulate the activity of the lncRNA. Notably, overexpression of Cerox1 transcript lacking miRNA binding sites did not rescue the memory deficit caused by SD. Our findings demonstrated that the impairment of memory consolidation after SD is linked to lncRNA-mediated control of mitochondrial electron transport chain activity essential for sustaining energy requirements.

Cytosolic and Membrane-Associated Ribosomes’ mRNA Profiles are Differentially Regulated by Learning and Sleep in Hippocampal Neurons

There is a general consensus that sleep is strictly linked to memory, learning, and, in general, to the mechanisms of neural plasticity, and that this link may directly affect recovery processes. In fact, a coherent pattern of empirical findings points to beneficial effect of sleep on learning and plastic processes, and changes in synaptic plasticity during wakefulness induce coherent modifications in EEG slow wave cortical topography during subsequent sleep. However, the specific nature of the relation between sleep and synaptic plasticity is not clear yet. We reported findings in line with two models conflicting with respect to the underlying mechanisms, that is, the “synaptic homeostasis hypothesis” and the “consolidation” hypothesis, and some recent results that may reconcile them. Independently from the specific mechanisms involved, sleep loss is associated with detrimental effects on plastic processes at a molecular and electrophysiological level. Finally, we reviewed growing evidence supporting the notion that plasticity-dependent recovery could be improved managing sleep quality, while monitoring EEG during sleep may help to explain how specific rehabilitative paradigms work. We conclude that a better understanding of the sleep-plasticity link could be crucial from a rehabilitative point of view.

PrPC is a glycoprotein capable to interact with several molecules and mediates diverse signaling pathways. Among numerous ligands, laminin (LN) is known to promote neurite outgrowth and memory consolidation, while amyloid‐beta oligomers (Aβo) trigger synaptic dysfunction. In both pathways, mGluR1 is recruited as co‐receptor. The involvement of PrPC/mGluR1 in these opposite functions suggests that this complex is a key element in the regulation of synaptic activity. Considering that sleep‐wake cycle is important for synaptic homeostasis, we aimed to investigate how sleep deprivation affects the expression of PrPC and its ligands, laminin, Aβo, and mGluR1, a multicomplex that can interfere with neuronal plasticity. To address this question, hippocampi of control (CT) and sleep deprived (SD) C57BL/6 mice were collected at two time points of circadian period (13 hr and 21 hr). We observed that sleep deprivation reduced PrPC and mGluR1 levels with higher effect in active state (21 hr). Sleep deprivation also caused accumulation of Aβ peptides in rest period (13 hr), while laminin levels were not affected. In vitro binding assay showed that Aβo can compete with LN for PrPC binding. The influence of Aβo was also observed in neuritogenesis. LN alone promoted longer neurite outgrowth than non‐treated cells in both Prnp+/+ and Prnp0/0 genotypes. Aβo alone did not show any effects, but when added together with LN, it attenuated the effects of LN only in Prnp+/+ cells. Altogether, our findings indicate that sleep deprivation regulates the availability of PrPC and Aβ peptides, and based on our in vitro assays, these alterations induced by sleep deprivation can negatively affect LN–PrPC interaction, which is known to play roles in neuronal plasticity.

Introduction: The human body operates according to an endogenous circadian cycle of approximately 24 h, regulated by the suprachiasmatic nucleus of the hypothalamus. This biological clock modulates essential physiological processes, including the sleep-wake cycle, hormonal secretion, and body temperature. Sleep, a complex and dynamic phenomenon, comprises alternating NREM and REM phases, each with distinct neurophysiological and cognitive functions. Recent evidence has increasingly highlighted sleep’s pivotal role in cognitive processes, particularly in the consolidation of memory. Objective: This study aimed to conduct a comprehensive review of current literature addressing the relationship between sleep hygiene, circadian rhythm, and memory consolidation, with a special focus on long-term memory. Methods: A descriptive bibliographic review was performed, analyzing articles published from 2019 to 2024 in PubMed, LILACS, and SciELO databases, using DeCS/MeSH descriptors: “sleep hygiene,” “sleep phases,” “memory consolidation,” “long-term memory,” and “circadian rhythm.” Results and discussions: The results demonstrate that deep NREM sleep significantly contributes to the consolidation of declarative and procedural memories, whereas REM sleep is essential for the processing of emotional content and the reorganization of neural circuits related to creative and adaptive functions. The synergistic action of neurotransmitters such as acetylcholine, serotonin, and melatonin are fundamental to these processes. Additionally, sleep deprivation, especially of REM sleep, is associated with cognitive deficits, impaired memory retention, and reduced emotional regulation. Conclusion: It is concluded that sleep should be recognized not merely as a period of rest, but as a biologically active state indispensable for neuroplasticity, cognitive resilience, and long-term memory stabilization.

Sleep supports memory consolidation, but the specific roles of different sleep stages in this process remain unclear. While rapid eye movement sleep (REM) has traditionally been linked to the processing of emotionally charged material, recent evidence suggests that slow wave sleep (SWS) also plays a role in strengthening emotional memories. Here, we use targeted memory reactivation (TMR) during REM and SWS in a daytime nap to directly examine which sleep stage is primarily involved in consolidating emotional declarative memories. Contrary to our hypothesis, reactivating emotional stimuli during REM impairs memory. Meanwhile, TMR benefit in SWS is strongly correlated with the product of time spent in REM and SWS. The emotional valence of cued items modulates both delta/theta power and sleep spindles. Furthermore, emotional memories benefit more from TMR than neutral ones. Our findings suggest that SWS and REM have complementary roles in consolidating emotional memories, with REM potentially involved in forgetting them. These results also expand on recent evidence highlighting a connection between sleep spindles and emotional processing.

One night of sleep deprivation induces a transient improvement in about 60% of depressed patients. Since depression is associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, the authors measured cortisol secretion before, during, and after therapeutic sleep deprivation for 1 night. Fifteen unmedicated depressed inpatients participated in a combined polysomnographic and endocrine study. Blood was sampled at 30-minute intervals during 3 consecutive nights before, during, and after sleep deprivation. Saliva samples were collected at 30-minute intervals during the daytime before and after the sleep deprivation night. During the night of sleep deprivation, cortisol levels were significantly higher than at baseline. During the daytime, cortisol levels during the first half of the day were higher than at baseline in the patients who responded to sleep deprivation but not in the nonresponders. During recovery sleep, cortisol secretion returned to baseline values. This study demonstrated a significant stimulatory effect of 1 night of sleep deprivation on the HPA axis in unmedicated depressed patients. The results suggest that the short-term effects of antidepressant treatments on the HPA axis may differ from their long-term effects. A higher cortisol level after sleep deprivation might transiently improve negative feedback to the hypothalamus or interact with other neurotransmitter systems, thus mediating or contributing to the clinical response. The fast return to baseline values coincides with the short clinical effect.