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Contrary to its well-established role in declarative learning, the impact of sleep on motor memory consolidation remains a subject of debate. Current literature suggests that while motor skill learning benefits from sleep, consolidation of sensorimotor adaptation (SMA) depends solely on the passage of time. This has led to the proposal that SMA may be an exception to other types of memories. Here, we addressed this ongoing controversy in humans through three comprehensive experiments using the visuomotor adaptation paradigm ( N  = 290, 150 females). In Experiment 1, we investigated the impact of sleep on memory retention when the temporal gap between training and sleep was not controlled. In line with the previous literature, we found that memory consolidates with the passage of time. In Experiment 2, we used an anterograde interference protocol to determine the time window during which SMA memory is most fragile and, thus, potentially most sensitive to sleep intervention. Our results show that memory is most vulnerable during the initial hour post-training. Building on this insight, in Experiment 3, we investigated the impact of sleep when it coincided with the critical first hour of memory consolidation. This manipulation unveiled a benefit of sleep (30% memory enhancement) alongside an increase in spindle density and spindle-SO coupling during NREM sleep, two well-established neural markers of sleep consolidation. Our findings reconcile seemingly conflicting perspectives on the active role of sleep in motor learning and point to common mechanisms at the basis of memory formation., Competing Interests: The authors declare no competing financial interest., (Copyright © 2024 the authors.)

The process of stabilization and storage of memories, known as consolidation, can be modulated by different interventions. Research has shown that self-regulation of brain activity through Neurofeedback (NFB) during the consolidation phase significantly impacts memory stabilization. While some studies have successfully modulated the consolidation phase using traditional EEG-based Neurofeedback (NFB) that focuses on general parameters, such as training a specific frequency band at particular electrodes, they often overlook the unique and complex neurodynamics that underlie each memory content in different individuals, potentially limiting the selective modulation of memories. The main objective of this study is to investigate the effects of a Subject-Dependent NFB (SD-NFB), based on individual models created from the brain activity of each participant, on long-term declarative memories. Participants underwent an experimental protocol involving three sessions. In the first session, they learned images of faces and houses while their brain activity was recorded. This EEG data was used to create individualized models to identify brain patterns related to learning these images. Participants were then divided into three groups, with one group receiving SD-NFB to enhance brain activity linked to faces, another to houses, and a CONTROL sham group that did not receive SD-NFB. Memory performance was evaluated 24 h and seven days later using an 'old-new' recognition task, where participants distinguished between 'old' and 'new' images. The results showed that memory contents (faces or houses) whose brain patterns were trained via SD-NFB scored lower in recognition compared to untrained contents, as evidenced 24 h and seven days post-training. In summary, this study demonstrates that SD-NFB can selectively impact the consolidation of specific declarative memories. This technique could hold significant implications for clinical applications, potentially aiding in the modulation of declarative memory strength in neuropsychiatric disorders where memories are pathologically exacerbated., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infusion of 17β-estradiol (E 2 ) into the dorsal hippocampus (DH) of ovariectomized (OVX) mice enhances memory consolidation, an effect that depends on rapid phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. Astrocytic glutamate transporter 1 (GLT-1) modulates neurotransmission via glutamate uptake from the synaptic cleft. However, little is known about the contribution of DH astrocytes, and astrocytic glutamate transport, to the memory-enhancing effects of E 2 . This study was designed to test whether DH astrocytes contribute to estrogenic modulation of memory consolidation by determining the extent to which DH GLT-1 is necessary for E 2 to enhance memory in object recognition and object placement tasks and trigger rapid phosphorylation events in DH astrocytes. OVX female mice were bilaterally cannulated into the DH or the DH and dorsal third ventricle (ICV). Post-training DH infusion of the GLT-1 inhibitor dihydrokainic acid (DHK) dose-dependently impaired memory consolidation in both tasks. Moreover, the memory-enhancing effects of ICV-infused E 2 in each task were blocked by DH DHK infusion. E 2 increased p42 ERK and Akt phosphorylation in DH astrocytes, and these effects were blocked by DHK. Results suggest the necessity of DH GLT-1 activity for object and spatial memory consolidation, and for E 2 to enhance consolidation of these memories and to rapidly activate cell signaling in DH astrocytes. Findings indicate that astrocytic function in the DH of OVX females is necessary for memory formation and is regulated by E 2 , and suggest an essential role for DH astrocytic GLT-1 activity in the memory-enhancing effects of E 2 ., Competing Interests: Declaration of competing interest Dr. Frick is a co-founder and the Chief Scientific Officer of Estrigenix Therapeutics, Inc., a company which aims to improve women's health by developing safe, clinically proven treatments for the mental and physical effects of menopause. The remaining authors have no conflicts of interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

While time spent in slow wave sleep (SWS) after learning promotes memory consolidation in the healthy brain, it is unclear if the same benefit is obtained in patients with temporal lobe epilepsy (TLE). Interictal epileptiform discharges (IEDs) are potentiated during SWS and thus may disrupt memory consolidation processes thought to depend on hippocampal-neocortical interactions. Here, we explored the relationship between SWS, IEDs, and overnight forgetting in patients with TLE. Nineteen patients with TLE studied object-scene pairs and memory was tested across a day of wakefulness (6 hrs) and across a night of sleep (16 hrs) while undergoing continuous scalp EEG monitoring. We found that time spent in SWS after learning was related to greater forgetting overnight. Longer duration in SWS and number of IEDs were each associated with greater forgetting, although the number of IEDs did not mediate the relationship between SWS and memory. Further research, particularly with intracranial recordings, is required to identify the mechanisms by which SWS and IEDs can be pathological to sleep-dependent memory consolidation in patients with TLE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sleep is essential in the process of memory consolidation. Children and adolescents with epilepsy hold a significantly higher risk for memory impairment. Understanding the relationship between sleep and memory impairment in adolescents with epilepsy will help us to develop effective support services for this patient population. The present study provides a summary of the current research on the influence of epilepsy-related altered sleep patterns on memory consolidation in children and adolescents with epilepsy. The aim of this systematic review is to investigate the influence of epilepsy-related altered sleep conditions in children and adolescents and their impact on memory performance., Materials: A systematic review was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the search terms "memory," "sleep," "epilepsy," "children," and "adolescents." A total of 4 studies met the inclusion criteria. The review focused on the association of sleep disorders and memory performance in children and adolescents aged up to 21 years without psychiatric comorbidities., Results: The reviewed studies highlight a higher risk of sleep disturbance and lower sleep quality in children with epilepsy in comparison to control groups. Group differences in memory consolidation were found before, but not after one night of sleep. Three studies reported a significant association between sleep and memory performance. Two studies demonstrated an association between nocturnal interictal epileptiform discharges and memory performance in adolescents., Conclusion: Children and adolescents with epilepsy have a higher risk of sleep and memory disorders. Nocturnal interictal epileptiform discharges have been shown to interfere with memory consolidation. Conclusions on underlying mechanisms remain unclear. Further case-control studies addressing sleep and its influence on memory problems in pediatric epilepsy patients are needed., Competing Interests: Declaration of competing interest The authors have nothing to report., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Labilization-reconsolidation, which relies on retrieval, has been considered an opportunity to attenuate the negative aspects of traumatic memories. A therapeutic strategy based on reconsolidation blockade is deemed more effective than current therapies relying on memory extinction. Nevertheless, extremely stressful memories frequently prove resistant to this process. Here, after inducing robust fear memory in mice through strong fear conditioning, we examined the possibility of rendering it susceptible to pharmacological modulation based on the degree of generalized fear (GF). To achieve this, we established an ordered gradient of GF, determined by the perceptual similarity between the associated context (CA) and non-associated contexts (CB, CC, CD, and CE) to the aversive event. We observed that as the exposure context became less similar to CA, the defensive pattern shifted from passive to active behaviors in both male and female mice. Subsequently, in conditioned animals, we administered propranolol after exposure to the different contexts (CA, CB, CC, CD or CE). In males, propranolol treatment resulted in reduced freezing time and enhanced risk assessment behaviors when administered following exposure to CA or CB, but not after CC, CD, or CE, compared to the control group. In females, a similar change in behavioral pattern was observed with propranolol administered after exposure to CC, but not after the other contexts. These results highlight the possibility of indirectly manipulating a robust contextual fear memory by controlling the level of generalization during recall. Additionally, it was demonstrated that the effect of propranolol on reconsolidation would not lead to a reduction in fear memory per se, but rather to its reorganization resulting in greater behavioral flexibility (from passive to active behaviors). Finally, from a clinical viewpoint, this would be of considerable relevance since following this strategy could make the treatment of psychiatric disorders associated with traumatic memory formation more effective and less stressful., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epigenetic factors are well-established players in memory formation. Specifically, DNA methylation is necessary for the formation of long-term memory in multiple brain regions including the hippocampus. Despite the demonstrated role of DNA methyltransferases (Dnmts) in memory formation, it is unclear whether individual Dnmts have unique or redundant functions in long-term memory formation. Furthermore, the downstream processes controlled by Dnmts during memory consolidation have not been investigated. In this study, we demonstrated that Dnmt3a1, the predominant Dnmt in the adult brain, is required for long-term spatial object recognition and contextual fear memory. Using RNA sequencing, we identified an activity-regulated Dnmt3a1-dependent genomic program in which several genes were associated with functional and structural plasticity. Furthermore, we found that some of the identified genes are selectively dependent on Dnmt3a1, but not its isoform Dnmt3a2. Specifically, we identified Neuropilin 1 (Nrp1) as a downstream target of Dnmt3a1 and further demonstrated the involvement of Nrp1 in hippocampus-dependent memory formation. Importantly, we found that Dnmt3a1 regulates hippocampus-dependent memory via Nrp1. In contrast, Nrp1 overexpression did not rescue memory impairments triggered by reduced Dnmt3a2 levels. Taken together, our study uncovered a Dnmt3a-isoform-specific mechanism in memory formation, identified a novel regulator of memory, and further highlighted the complex and highly regulated functions of distinct epigenetic regulators in brain function., (© 2024. The Author(s).)

Aromatase inhibitors (AIs) are associated with sleep difficulties in breast cancer (BC) patients. Sleep is known to favor memory consolidation through the occurrence of specific oscillations, i.e., slow waves (SW) and sleep spindles, allowing a dialogue between prefrontal cortex and the hippocampus. Interestingly, neuroimaging studies in BC patients have consistently shown structural and functional modifications in these two brain regions. With the aim to evaluate sleep oscillations related to memory consolidation during AIs, we collected polysomnography data in BC patients treated (AI+, n = 17) or not (AI-, n = 17) with AIs compared to healthy controls (HC, n = 21). None of the patients had received chemotherapy and radiotherapy was finished since at least 6 months, that limit the confounding effects of other treatments than AIs. Fast and slow spindles were detected during sleep stage 2 at centro-parietal and frontal electrodes respectively. SW were detected at frontal electrodes during stage 3. Here, we show lower frontal SW densities in AI + patients compared to HC. These results concord with previous reports about frontal cortical alterations in cancer following AIs administration. Moreover, AI + patients tended to have lower spindle density at C4 electrode. Regression analyses showed that, in both patient groups, spindle density at C4 electrode explained a large variance of memory performances. Slow spindle characteristics did not differ between groups and sleep oscillations characteristics of AI- patients did not differ significantly from those of both AI + patients and HC. Overall, our results add to the compelling evidence of the systemic effects of AIs previously reported in animals, with deleterious effects on cortical activity during sleep and associated memory consolidation in the current study. There is thus a need to further investigate sleep modifications during AIs administration. Longitudinal studies are needed to confirm these findings and investigation in other cancers on this topic should be conducted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. The output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets. We previously showed that treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Furthermore, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue., (© 2024. The Author(s).)

Post-traumatic stress disorder (PTSD) is a psychiatric disorder with traumatic memories at its core. Post-treatment sleep may offer a unique time window to increase therapeutic efficacy through consolidation of therapeutically modified traumatic memories. Targeted memory reactivation (TMR) enhances memory consolidation by presenting reminder cues (e.g., sounds associated with a memory) during sleep. Here, we applied TMR in PTSD patients to strengthen therapeutic memories during sleep after one treatment session with eye movement desensitization and reprocessing (EMDR). PTSD patients received either slow oscillation (SO) phase-targeted TMR, using modeling-based closed-loop neurostimulation (M-CLNS) with EMDR clicks as a reactivation cue (n = 17), or sham stimulation (n = 16). Effects of TMR on sleep were assessed through high-density polysomnography. Effects on treatment outcome were assessed through subjective, autonomic, and fMRI responses to script-driven imagery (SDI) of the targeted traumatic memory and overall PTSD symptom level. Compared to sham stimulation, TMR led to stimulus-locked increases in SO and spindle dynamics, which correlated positively with PTSD symptom reduction in the TMR group. Given the role of SOs and spindles in memory consolidation, these findings suggest that TMR may have strengthened the consolidation of the EMDR-treatment memory. Clinically, TMR vs. sham stimulation resulted in a larger reduction of avoidance level during SDI. TMR did not disturb sleep or trigger nightmares. Together, these data provide first proof of principle that TMR may be a safe and viable future treatment augmentation strategy for PTSD. The required follow-up studies may implement multi-night TMR or TMR during REM sleep to further establish the clinical effect of TMR for traumatic memories., Competing Interests: Declaration of interests International patent application WO2018156021 of University of Amsterdam and Okazolab LtD, inventors: L.M.T. and Korjoukov, Ilia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Memory reactivation requires counterbalancing to consolidate memories.

Memory consolidation involves the synchronous reactivation of hippocampal cells active during recent experience in sleep sharp-wave ripples (SWRs). How this increase in firing rates and synchrony after learning is counterbalanced to preserve network stability is not understood. We discovered a network event generated by an intrahippocampal circuit formed by a subset of CA2 pyramidal cells to cholecystokinin-expressing (CCK+) basket cells, which fire a barrage of action potentials ("BARR") during non-rapid eye movement sleep. CA1 neurons and assemblies that increased their activity during learning were reactivated during SWRs but inhibited during BARRs. The initial increase in reactivation during SWRs returned to baseline through sleep. This trend was abolished by silencing CCK+ basket cells during BARRs, resulting in higher synchrony of CA1 assemblies and impaired memory consolidation.

Studies using magnetic brain stimulation indicate the involvement of somatosensory regions in the acquisition and retention of newly learned movements. Recent work found an impairment in motor memory when retention was tested shortly after the application of continuous theta-burst stimulation (cTBS) to the primary somatosensory cortex, compared with stimulation of the primary motor cortex or a control zone. This finding that the somatosensory cortex is involved in motor memory retention whereas the motor cortex is not, if confirmed, could alter our understanding of human motor learning. It would indicate that plasticity in sensory systems underlies newly learned movements, which is different than the commonly held view that adaptation learning involves updates to a motor controller. Here we test this idea. Participants were trained in a visuomotor adaptation task, with visual feedback gradually shifted. Following adaptation, cTBS was applied either to M1, S1, or an occipital cortex control area. Participants were tested for retention 24 h later. It was observed that S1 stimulation led to reduced retention of prior learning, compared with stimulation of M1 or the control area (with no significant difference between M1 and control). In a further control, cTBS was applied to S1 following training with unrotated feedback, in which no learning occurred. This had no effect on movement in the retention test indicating the effects of S1 stimulation on movement are learning specific. The findings are consistent with the S1 participation in the encoding of learning-related changes to movements and in the retention of human motor memory., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

The effects of intra-hippocampal manipulation of glycine receptors on the reconsolidation of recent and late long-term spatial memory were evaluated and assessed in the Morris water maze. The results obtained from the intra-hippocampal infusion of glycine and taurine demonstrated that taurine at a 100 nmol/side dose impaired the reconsolidation of recent and late long-term spatial memory. In comparison, at a dose of 10 nmol/side, it only affected the reconsolidation of late long-term spatial memory, reinforcing that there are differences between molecular mechanisms underlying recent and late long-term memory reconsolidation. On the other hand, glycine impaired the reconsolidation of early and late spatial memory when infused at a dose of 10 nmol/side, but not at a dose of 100 nmol/side, unless it is co-infused with an allosteric site antagonist of the NMDA receptor. Altogether these results show that glycine acting in situ in the hippocampal CA1 region exerts a pharmacological effect on U-curve, which can be explained by its concomitant action on its ionotropic receptor GlyR and on its NMDA receptor co-agonist site., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Experimental findings showing that retrieved memories are labile and vulnerable to disruption have led to important theoretical ideas at a basic science level that have been applied to the clinic at a translational level. At a theoretical level, these findings suggest that retrieved memories can be modulated by behavioral or pharmacological treatments as they are reconsolidated and returned to storage. At a clinical level, these findings suggest that treatments that target reconsolidation may help dampen or even erase especially problematic memories, such as those associated with trauma. However, there are many caveats to these effects and issues that need to be considered when thinking broadly about retrieval-induced plasticity and extensions into the clinic. First, performance during a memory test often does not reflect the entirety of the animal's knowledge about a situation; asking questions in different ways may reveal the presence of a memory that was thought to be eliminated. Second, although reconsolidation and extinction are often treated as competing processes, there is abundant evidence that extinction can progress through associative and nonassociative changes in the original memory that are often described in terms of reconsolidation effects. Third, targeting a reconsolidation process as a therapeutic may not be helpful in disorders like posttraumatic stress disorder, in which traumatic experiences induce a cascade of symptoms that are self-perpetuating and may ultimately maintain themselves long after trauma. Underlying all of these challenges is the need for a rich theoretical framework focused on retrieval-induced plasticity that is informed by developments in associative learning theory. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Experimental studies suggest that short or disrupted sleep impairs memory consolidation, mood, and perception of emotional stimuli. However, studies have chiefly relied on laboratory-based study designs and small sample sizes. The aim of this fully online and pre-registered study was to investigate the association between sleep and overnight memory consolidation, emotion perception, and affect in a large, self-selected UK sample. A total of 1646 participants (473 completed) took part in an online study, where they completed a declarative (word-pairs) memory task, emotion perception task (valence ratings of images), and rated their affect within 2 h of bed-time. The following morning, participants reported on their state affect, sleep for the previous night, completed a cued recall task for the previously presented word-pairs, rated the valence of previously viewed images, and completed a surprise recognition task. Demographic data and habitual sleep quality and duration (sleep traits) were also recorded. Habitual sleep traits were associated with immediate recall for the word-pairs task, while self-reported sleep parameters for the specific night were not associated with overnight memory consolidation. Neither habitual sleep traits, nor nightly sleep parameters were associated with unpleasantness ratings to negative stimuli or overnight habituation. Habitual poor sleep was associated with less positive and more negative affect, and morning affect was predicted by the specific night's sleep. This study suggests that overnight emotional processing and declarative memory may not be associated with self-reported sleep across individuals. More work is needed to understand how findings from laboratory-based studies extrapolate to real-world samples and contexts., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Infants face the constant challenge of selecting information for encoding and storage from a continuous incoming stream of data. Sleep might help in this process by selectively consolidating new memory traces that are likely to be of future relevance. Using a deferred imitation paradigm and an experimental design, we asked whether 15- and 24-month-old infants (N = 105) who slept soon after encoding a televised demonstration of target actions would show higher imitation scores (retention) after a 24-h delay than same-aged infants who stayed awake for ≥4 h after encoding. In light of infants' well-known difficulties in learning and remembering information from screens, we tested if increasing the relevance of the televised content via standardised caregiver verbalisations might yield the highest imitation scores in the sleep condition. Regardless of sleep condition, 24-month-olds exhibited retention of target actions while 15-month-olds consistently failed to do so. For 24-month-olds, temporal recall was facilitated by sleep, but not by parental verbalisations. Correlational analyses revealed that more time asleep within 4 h after encoding was associated with better retention of the target actions and their temporal order in 24-months-olds. These results suggest that sleep facilitates memory consolidation of screen-based content in late infancy and that this effect might not hinge on caregivers' verbal engagement during viewing., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Previous studies have demonstrated that conventional transcranial direct current stimulation (tDCS) can enhance novel-word learning. However, because of the widespread current that is induced by these setups and lack of appropriate control conditions, little is known about the underlying neural mechanisms. In the present double-blinded and sham-tDCS controlled study, we investigated for the first time if regionally precise focal tDCS targeting two key nodes of the novel-word learning network at different time points would result in regionally and temporally distinct effects. 156 participants completed a contextual novel-word-learning paradigm and learning success was probed immediately after the acquisition period and 30-min later. Participants were randomly assigned to six stimulation conditions: Active tDCS (1.5 mA) was administered to left inferior frontal (IFG) or middle temporal gyrus (MTG), either during acquisition or delayed recall. Control groups received sham-tDCS either during acquisition or delayed recall (50% IFG/MTG). Data were analyzed with a generalized linear mixed model with a binomial link function in a Bayesian framework. Our results showed that frontal tDCS selectively increased accuracy gains from immediate to delayed recall, irrespective of timing of the stimulation. There was no evidence for beneficial effects of middle temporal gyrus tDCS. Our findings confirm that IFG tDCS can enhance novel-word learning in a regionally, but not timing specific way. Tentatively, this may be explained by enhancement of semantic selection processes resulting in more effective consolidation and/or retrieval. Future studies using longer time intervals between assessments are required to clarify the potential contribution of neurophysiological after-effects of IFG tDCS administered during acquisition to enhanced consolidation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Motor adaptation reflects the ability of the brain's sensorimotor system to flexibly deal with environmental changes to generate effective motor behaviour. Whether sleep contributes to the consolidation of motor adaptation remains controversial. In this study, we investigated the impact of sleep on motor adaptation and its neurophysiological correlates in a novel motor adaptation task that leverages a highly automatised motor skill, that is, typing. We hypothesised that sleep-associated memory consolidation would benefit motor adaptation and induce modulations in task-related beta band (13-30 Hz) activity during adaptation. Healthy young male experts in typing on the regular computer keyboard were trained to type on a vertically mirrored keyboard while brain activity was recorded using electroencephalography. Typing performance was assessed either after a full night of sleep with polysomnography or a similar period of daytime wakefulness. Results showed improved motor adaptation performance after nocturnal sleep but not after daytime wakefulness, and decreased beta power: (a) during mirrored typing as compared with regular typing; and (b) in the post-sleep versus the pre-sleep mirrored typing sessions. Furthermore, the slope of the electroencephalography signal, a measure of aperiodic brain activity, decreased during mirrored as compared with regular typing. Changes in the electroencephalography spectral slope from pre- to post-sleep mirrored typing sessions were correlated with changes in task performance. Finally, increased fast sleep spindle density (13-15 Hz) during the night following motor adaptation training was predictive of successful motor adaptation. These findings suggest that post-training sleep modulates neural activity supporting adaptive motor functions., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Acute exercise has been shown to affect long-term memory and sleep. However, it is unclear whether exercise-induced changes in sleep architecture are associated with enhanced memory. Recently, it has been shown that exercise followed by a nap improved declarative memory. Whether these effects transfer to night sleep and other memory domains has not yet been studied. Here, we investigate the influence of exercise on nocturnal sleep architecture and associations with sleep-dependent procedural and declarative memory consolidation. Nineteen subjects (23.68 ± 3.97 years) were tested in a balanced cross-over design. In two evening sessions, participants either exercised (high-intensity interval training) or rested immediately after encoding two memory tasks: (1) a finger tapping task and (2) a paired-associate learning task. Subsequent nocturnal sleep was recorded by polysomnography. Retrieval was conducted the following morning. High-intensity interval training lead to an increased declarative memory retention (p = 0.047, d = 0.40) along with a decrease in REM sleep (p = 0.012, d = 0.75). Neither procedural memory nor NREM sleep were significantly affected. Exercise-induced changes in N2 showed a positive correlation with procedural memory retention which did not withstand multiple comparison correction. Exploratory analyses on sleep spindles and slow wave activity did not reveal significant effects. The present findings suggest an exercise-induced enhancement of declarative memory which aligns with changes in nocturnal sleep architecture. This gives additional support for the idea of a potential link between exercise-induced sleep modifications and memory formation which requires further investigation in larger scaled studies., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Empirical investigations that search for a link between dreaming and sleep-dependent memory consolidation have focused on testing for an association between dreaming of what was learned, and improved memory performance for learned material. Empirical support for this is mixed, perhaps owing to the inherent challenges presented by the nature of dreams, and methodological inconsistencies. The purpose of this paper is to address critically prevalent assumptions and practices, with the aim of clarifying and enhancing research on this topic, chiefly by providing a theoretical synthesis of existing models and evidence. Also, it recommends the method of Targeted Memory Reactivation (TMR) as a means for investigating if dream content can be linked to specific cued activations. Other recommendations to enhance research practice and enquiry on this subject are also provided, focusing on the HOW and WHY we search for memory sources in dreams, and what purpose (if any) they might serve., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Social communication guides decision-making, which is essential for survival. Social transmission of food preference (STFP) is an ecologically relevant memory paradigm in which an animal learns a desirable food odour from another animal in a social context, creating a long-term memory 1,2 . How food-preference memory is acquired, consolidated and stored is unclear. Here we show that the posteromedial nucleus of the cortical amygdala (COApm) serves as a computational centre in long-term STFP memory consolidation by integrating social and sensory olfactory inputs. Blocking synaptic signalling by the COApm-based circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage or recall. COApm-mediated STFP memory consolidation depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus. STFP memory consolidation requires protein synthesis, suggesting a gene-expression mechanism. Deep single-cell and spatially resolved transcriptomics revealed robust but distinct gene-expression signatures induced by STFP memory formation in the COApm that are consistent with synapse restructuring. Our data thus define a neural circuit for the consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein-synthesis-dependent memory consolidation from memory acquisition, storage or retrieval., (© 2024. The Author(s).)

Memory consolidation refers to a process by which labile newly formed memory traces are progressively strengthened into long term memories and become more resistant to interference. Recent work has revealed that spontaneous hippocampal activity during rest, commonly referred to as "offline" activity, plays a critical role in the process of memory consolidation. Hippocampal reactivation occurs during sharp-wave ripples (SWRs), which are events associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Memory consolidation occurs primarily through a coordinated communication between hippocampus and neocortex. Cortical slow oscillations drive the repeated reactivation of hippocampal memory representations together with SWRs and thalamo-cortical spindles, inducing long-lasting cellular and network modifications responsible for memory stabilization.In this review, we aim to comprehensively cover the field of "reactivation and memory consolidation" research by detailing the physiological mechanisms of neuronal reactivation and firing patterns during SWRs and providing a discussion of more recent key findings. Several mechanistic explanations of neuropsychiatric diseases propose that impaired neural replay may underlie some of the symptoms of the disorders. Abnormalities in neuronal reactivation are a common phenomenon and cause pathological impairment in several diseases, such as Alzheimer's disease (AD), epilepsy and schizophrenia. However, the specific pathological changes and mechanisms of reactivation in each disease are different. Recent work has also enlightened some of the underlying pathological mechanisms of neuronal reactivation in these diseases. In this review, we further describe how SWRs, ripples and slow oscillations are affected in Alzheimer's disease, epilepsy, and schizophrenia. We then compare the differences of neuronal reactivation and discuss how different reactivation abnormalities cause pathological changes in these diseases. Aberrant neural reactivation provides insights into disease pathogenesis and may even serve as biomarkers for early disease progression and treatment response., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Theoretical models conventionally portray the consolidation of memories as a slow process that unfolds during sleep. According to the classical Complementary Learning Systems theory, the hippocampus (HPC) rapidly changes its connectivity during wakefulness to encode ongoing events and create memory ensembles that are later transferred to the prefrontal cortex (PFC) during sleep. However, recent experimental studies challenge this notion by showing that new information consistent with prior knowledge can be rapidly consolidated in PFC during wakefulness and that PFC lesions disrupt the encoding of congruent events in the HPC. The contributions of the PFC to memory encoding have therefore largely been overlooked. Moreover, most theoretical frameworks assume random and uncorrelated patterns representing memories, disregarding the correlations between our experiences. To address these shortcomings, we developed a HPC-PFC network model that simulates interactions between the HPC and PFC during the encoding of a memory (awake stage), and subsequent consolidation (sleeping stage) to examine the contributions of each region to the consolidation of novel and congruent memories. Our results show that the PFC network uses stored memory "schemas" consolidated during previous experiences to identify inputs that evoke congruent patterns of activity, quickly integrate it into its network, and gate which components are encoded in the HPC. More specifically, the PFC uses GABAergic long-range projections to inhibit HPC neurons representing input components correlated with a previously stored memory "schema," eliciting sparse hippocampal activity during exposure to congruent events, as it has been experimentally observed., Competing Interests: Competing interests statement:The authors declare no competing interest.

In a variety of species and behavioral contexts, learning and memory formation recruits two neural systems, with initial plasticity in one system being consolidated into the other over time. Moreover, consolidation is known to be selective; that is, some experiences are more likely to be consolidated into long-term memory than others. Here, we propose and analyze a model that captures common computational principles underlying such phenomena. The key component of this model is a mechanism by which a long-term learning and memory system prioritizes the storage of synaptic changes that are consistent with prior updates to the short-term system. This mechanism, which we refer to as recall-gated consolidation, has the effect of shielding long-term memory from spurious synaptic changes, enabling it to focus on reliable signals in the environment. We describe neural circuit implementations of this model for different types of learning problems, including supervised learning, reinforcement learning, and autoassociative memory storage. These implementations involve synaptic plasticity rules modulated by factors such as prediction accuracy, decision confidence, or familiarity. We then develop an analytical theory of the learning and memory performance of the model, in comparison to alternatives relying only on synapse-local consolidation mechanisms. We find that recall-gated consolidation provides significant advantages, substantially amplifying the signal-to-noise ratio with which memories can be stored in noisy environments. We show that recall-gated consolidation gives rise to a number of phenomena that are present in behavioral learning paradigms, including spaced learning effects, task-dependent rates of consolidation, and differing neural representations in short- and long-term pathways., Competing Interests: JL, AL No competing interests declared, (© 2023, Lindsey and Litwin-Kumar.)

We examined how aging affects the role of sleep in the consolidation of newly learned cognitive strategies. Forty healthy young adults (20-35 years) and 30 healthy older adults (60-85 years) were included. Participants were trained on the Tower of Hanoi (ToH) task, then, half of each age group were assigned to either the 90-minute nap condition, or stayed awake, before retesting. The temporal co-occurrence between slow waves (SW) and sleep spindles (SP) during non-rapid eye movement sleep was examined as a function of age in relation to memory consolidation of problem-solving skills. We found that despite intact learning, older adults derived a reduced benefit of sleep for problem-solving skills relative to younger adults. As expected, the percentage of coupled spindles was lower in older compared to younger individuals from control to testing sessions. Furthermore, coupled spindles in young adults were more strongly coupled to the SW upstate compared to older individuals. Coupled spindles in older individuals were lower in amplitude (mean area under the curve; μV) compared to the young group. Lastly, there was a significant relationship between offline gains in accuracy on the ToH and percent change of spindles coupled to the upstate of the slow wave in older, but not younger adults. Multiple regression revealed that age accounted for differences in offline gains in accuracy, as did spindle coupling during the upstate. These results suggest that with aging, spindle-slow wave coupling decreases. However, the degree of the preservation of coupling with age correlates with the extent of problem-solving skill consolidation during sleep., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Purpose: Previous studies have reported the success of distributional learning for adult speakers across segmental and suprasegmental categories immediately after training. On the other hand, second language (L2) perception models posit that the ease with which learners perceive a nonnative speech contrast depends on the perceptual mapping between the contrast and learners' first language (L1) categories. This study examined whether a difference in perceptual mapping patterns for different L2-Mandarin tonal contrasts might result in a difference in distributional learning effectiveness for tonal speakers and whether an interval of sleep enhanced the knowledge through consolidation., Method: Following a pretest-training-posttest design, 66 L1-Cantonese participants with fewer than 9 years of Mandarin training were assigned to either the bimodal or unimodal distribution conditions. The participants of each group were asked to discriminate Mandarin level-falling (T1-T4) and level-rising (T1-T2) tone pairs on novel syllables in a within-subject design. All participants were trained in the evening, tested after training, and returned after 12 hr for overnight consolidation assessment., Results: A significant distributional learning effect was observed for Mandarin T1-T4, but only after sleep. No significant distributional learning effect was observed for Mandarin T1-T2, either after training or after sleep., Conclusions: The findings may imply that distributional learning is contingent on perceptual mapping patterns of the target contrasts and that sleep may play a role in the consolidation of knowledge in an implicit statistical learning paradigm., Supplemental Material: https://doi.org/10.23641/asha.25970008.

Memory consolidation is the process of translating memory traces from the hippocampus to the cortex. Hippocampal ripples are key in driving this transfer. A new study now shows that independent cortical ripples can suppress this communication. What could be the underlying mechanisms?, Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Consolidation of initially encoded hippocampal representations in the neocortex through reactivation is crucial for long-term memory formation and is facilitated by the coordination of hippocampal sharp-wave ripples (SWRs) with cortical slow and spindle oscillations during non-REM sleep. Recent evidence suggests that high-frequency cortical ripples can also coordinate with hippocampal SWRs in support of consolidation; however, the contribution of cortical ripples to reactivation remains unclear. We used high-density, continuous recordings in the hippocampus (area CA1) and prefrontal cortex (PFC) over the course of spatial learning and show that independent PFC ripples dissociated from SWRs are prevalent in NREM sleep and predominantly suppress hippocampal activity. PFC ripples paradoxically mediate top-down suppression of hippocampal reactivation rather than coordination, and this suppression is stronger for assemblies that are reactivated during coordinated CA1-PFC ripples for consolidation of recent experiences. Further, we show non-canonical, serial coordination of independent cortical ripples with slow and spindle oscillations, which are known signatures of memory consolidation. These results establish a role for prefrontal cortical ripples in top-down regulation of behaviorally relevant hippocampal representations during consolidation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The standard consolidation theory states that short-term memories located in the hippocampus enable the consolidation of long-term memories in the neocortex. In other words, the neocortex slowly learns long-term memories with a transient support of the hippocampus that quickly learns unstable memories. However, it is not clear yet what could be the neurobiological mechanisms underlying these differences in learning rates and memory time-scales. Here, we propose a novel modeling approach of the standard consolidation theory, that focuses on its potential neurobiological mechanisms. In addition to synaptic plasticity and spike frequency adaptation, our model incorporates adult neurogenesis in the dentate gyrus as well as the difference in size between the neocortex and the hippocampus, that we associate with distance-dependent synaptic plasticity. We also take into account the interconnected spatial structure of the involved brain areas, by incorporating the above neurobiological mechanisms in a coupled neural field framework, where each area is represented by a separate neural field with intra- and inter-area connections. To our knowledge, this is the first attempt to apply neural fields to this process. Using numerical simulations and mathematical analysis, we explore the short-term and long-term dynamics of the model upon alternance of phases of hippocampal replay and retrieval cue of an external input. This external input is encodable as a memory pattern in the form of a multiple bump attractor pattern in the individual neural fields. In the model, hippocampal memory patterns become encoded first, before neocortical ones, because of the smaller distances between the bumps of the hippocampal memory patterns. As a result, retrieval of the input pattern in the neocortex at short time-scales necessitates the additional input delivered by the memory pattern of the hippocampus. Neocortical memory patterns progressively consolidate at longer times, up to a point where their retrieval does not need the support of the hippocampus anymore. At longer times, perturbation of the hippocampal neural fields by neurogenesis erases the hippocampus pattern, leading to a final state where the memory pattern is exclusively evoked in the neocortex. Therefore, the dynamics of our model successfully reproduces the main features of the standard consolidation theory. This suggests that neurogenesis in the hippocampus and distance-dependent synaptic plasticity coupled to synaptic depression and spike frequency adaptation, are indeed critical neurobiological processes in memory consolidation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hippocampal replay - the time-compressed, sequential reactivation of ensembles of neurons related to past experience - is a key neural mechanism of memory consolidation. Replay typically coincides with a characteristic pattern of local field potential activity, the sharp-wave ripple (SWR). Reduced SWR rates are associated with cognitive impairment in multiple models of neurodegenerative disease, suggesting that a clinically viable intervention to promote SWRs and replay would prove beneficial. We therefore developed a neurofeedback paradigm for rat subjects in which SWR detection triggered rapid positive feedback in the context of a memory-dependent task. This training protocol increased the prevalence of task-relevant replay during the targeted neurofeedback period by changing the temporal dynamics of SWR occurrence. This increase was also associated with neural and behavioral forms of compensation after the targeted period. These findings reveal short-timescale regulation of SWR generation and demonstrate that neurofeedback is an effective strategy for modulating hippocampal replay., Competing Interests: AG, LF U.S. Patent Application No. 62/887,875 on SWR modulation via neurofeedback has been filed by the University of California, San Francisco with AKG and LMF listed as inventors, DA, ED, SD No competing interests declared, (© 2023, Gillespie et al.)

It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human observers often exhibit remarkable consistency in remembering specific visual details, such as certain face images. This phenomenon is commonly attributed to visual memorability, a collection of stimulus attributes that enhance the long-term retention of visual information. However, the exact contributions of visual memorability to visual memory formation remain elusive as these effects could emerge anywhere from early perceptual encoding to post-perceptual memory consolidation processes. To clarify this, we tested three key predictions from the hypothesis that visual memorability facilitates early perceptual encoding that supports the formation of visual short-term memory (VSTM) and the retention of visual long-term memory (VLTM). First, we examined whether memorability benefits in VSTM encoding manifest early, even within the constraints of a brief stimulus presentation (100-200 ms; Experiment 1). We achieved this by manipulating stimulus presentation duration in a VSTM change detection task using face images with high- or low-memorability while ensuring they were equally familiar to the participants. Second, we assessed whether this early memorability benefit increases the likelihood of VSTM retention, even with post-stimulus masking designed to interrupt post-perceptual VSTM consolidation processes (Experiment 2). Last, we investigated the durability of memorability benefits by manipulating memory retention intervals from seconds to 24 h (Experiment 3). Across experiments, our data suggest that visual memorability has an early impact on VSTM formation, persisting across variable retention intervals and predicting subsequent VLTM overnight. Combined, these findings highlight that visual memorability enhances visual memory within 100-200 ms following stimulus onset, resulting in robust memory traces resistant to post-perceptual interruption and long-term forgetting., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare with respect to the authorship or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recognizing and remembering another individual in a social context could be beneficial for individual fitness. Especially in agonistic encounters, remembering an opponent and the previous fight could allow for avoiding new conflicts. Considering this, we hypothesized that this type of social interaction forms a long-term recognition memory lasting several days. It has been shown that a second encounter 24 h later between the same pair of zebrafish males is resolved with lower levels of aggression. Here, we evaluated if this behavioral change could last for longer intervals and a putative mechanism associated with memory storage: the recruitment of NMDA receptors. We found that if a pair of zebrafish males fight and fight again 48 or 72 h later, they resolve the second encounter with lower levels of aggression. However, if opponents were exposed to MK-801 (NMDA receptor antagonist) immediately after the first encounter, they solved the second one with the same levels of aggression: that is, no reduction in aggressive behaviors was observed. These amnesic effect suggest the formation of a long-term social memory related to recognizing a particular opponent and/or the outcome and features of a previous fight., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Long-term memories are believed to be encoded by unique transcriptional signatures in the brain. The expression of immediate early genes (IEG) promotes structural and molecular changes required for memory consolidation. Recent evidence has shown that the brain is equipped with mechanisms that not only promote, but actively constrict memory formation. However, it remains unknown whether IEG expression may play a role in memory suppression. Here we uncovered a novel function of the IEG neuronal PAS domain protein 4 (Npas4), as an inducible memory suppressor gene of highly salient aversive experiences. Using a contextual fear conditioning paradigm, we found that low stimulus salience leads to monophasic Npas4 expression, while highly salient learning induces a biphasic expression of Npas4 in the hippocampus. The later phase requires N-methyl-D-aspartate (NMDA) receptor activity and is independent of dopaminergic neurotransmission. Our in vivo pharmacological and genetic manipulation experiments suggested that the later phase of Npas4 expression restricts the consolidation of a fear memory and promote behavioral flexibility, by facilitating fear extinction and the contextual specificity of fear responses. Moreover, immunofluorescence and electrophysiological analysis revealed a concomitant increase in synaptic input from cholecystokinin (CCK)-expressing interneurons. Our results demonstrate how salient experiences evoke unique temporal patterns of IEG expression that fine-tune memory consolidation. Moreover, our study provides evidence for inducible gene expression associated with memory suppression as a possible mechanism to balance the consolidation of highly salient memories, and thereby to evade the formation of maladaptive behavior., (© 2024. The Author(s).)

Study Objectives: Sleep is required for successful memory consolidation. Sleep spindles, bursts of oscillatory activity occurring during non-rapid eye movement sleep, are known to be crucial for this process and, recently, it has been proposed that the temporal organization of spindles into clusters might additionally play a role in memory consolidation. In Parkinson's disease, spindle activity is reduced, and this reduction has been found to be predictive of cognitive decline. However, it remains unknown whether alterations in sleep spindles in Parkinson's disease are predictive of sleep-dependent cognitive processes such as memory consolidation, leaving open questions about the possible mechanisms linking sleep and a more general cognitive state in Parkinson's patients., Methods: The current study sought to fill this gap by recording overnight polysomnography and measuring overnight declarative memory consolidation in a sample of 35 patients with Parkinson's. Memory consolidation was measured using a verbal paired-associates task administered before and after the night of recorded sleep., Results: We found that lower sleep spindle density at frontal leads during non-rapid eye movement stage 3 was associated with worse overnight declarative memory consolidation. We also found that patients who showed less temporal clustering of spindles exhibited worse declarative memory consolidation., Conclusions: These results suggest alterations to sleep spindles, which are known to be a consequence of Parkinson's disease, might represent a mechanism by which poor sleep leads to worse cognitive function in Parkinson's patients., Citation: Lahlou S, Kaminska M, Doyon J, Carrier J, Sharp M. Sleep spindle density and temporal clustering are associated with sleep-dependent memory consolidation in Parkinson's disease. J Clin Sleep Med . 2024;20(7):1153-1162., (© 2024 American Academy of Sleep Medicine.)

A short period of eyes-closed waking rest improves long-term memory for recently learned information, including declarative, spatial, and procedural memory. However, the effect of rest on emotional memory consolidation remains unknown. This preregistered study aimed to establish whether post-encoding rest affects emotional memory and how anxiety levels might modulate this effect. Participants completed a modified version of the dot-probe attention task that involved reacting to and encoding word stimuli appearing underneath emotionally negative or neutral photos. We tested the effect of waking rest on memory for these words and pictures by manipulating the state that participants entered just after this task (rest vs. active wake). Trait anxiety levels were measured using the State-Trait Anxiety Inventory and examined as a covariate. Waking rest improved emotional memory consolidation for individuals high in trait anxiety. These results suggest that the beneficial effect of waking rest on memory extends into the emotional memory domain but depends on individual characteristics such as anxiety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spontaneous reactivation of brain activity from learning to a subsequent off-line period has been implicated as a neural mechanism underlying memory consolidation. However, similarities in brain activity may also emerge as a result of individual, trait-like characteristics. Here, we introduced a novel approach for analyzing continuous electroencephalography (EEG) data to investigate learning-induced changes as well as trait-like characteristics in brain activity underlying memory consolidation. Thirty-one healthy young adults performed a learning task, and their performance was retested after a short (∼1 h) delay. Consolidation of two distinct types of information (serial-order and probability) embedded in the task were tested to reveal similarities in functional networks that uniquely predict the changes in the respective memory performance. EEG was recorded during learning and pre- and post-learning rest periods. To investigate brain activity associated with consolidation, we quantified similarities in EEG functional connectivity between learning and pre-learning rest (baseline similarity) and learning and post-learning rest (post-learning similarity). While comparable patterns of these two could indicate trait-like similarities, changes from baseline to post-learning similarity could indicate learning-induced changes, possibly spontaneous reactivation. Higher learning-induced changes in alpha frequency connectivity (8.5-9.5 Hz) were associated with better consolidation of serial-order information, particularly for long-range connections across central and parietal sites. The consolidation of probability information was associated with learning-induced changes in delta frequency connectivity (2.5-3 Hz) specifically for more local, short-range connections. Furthermore, there was a substantial overlap between the baseline and post-learning similarities and their associations with consolidation performance, suggesting robust (trait-like) differences in functional connectivity networks underlying memory processes., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Growing evidence indicates a critical role of astrocytes in learning and memory. However, little is known about the role of basolateral amygdala complex (BLA-C) astrocytes in contextual fear conditioning (CFC), a paradigm relevant to understand and generate treatments for fear- and anxiety-related disorders. To get insights on the involvement of BLA-C astrocytes in fear memory, fluorocitrate (FLC), a reversible astroglial metabolic inhibitor, was applied at critical moments of the memory processing in order to target the acquisition, consolidation, retrieval and reconsolidation process of the fear memory. Adult Wistar male rats were bilaterally cannulated in BLA-C. Ten days later they were infused with different doses of FLC (0.5 or 1 nmol/0.5 µl) or saline before or after CFC and before or after retrieval. FLC impaired fear memory expression when administered before and shortly after CFC, but not one hour later. Infusion of FLC prior and after retrieval did not affect the memory. Our findings suggest that BLA-C astrocytes are critically involved in the acquisition/early consolidation of fear memory but not in the retrieval and reconsolidation. Furthermore, the extinction process was presumably not affected (considering that peri-retrieval administration could also affect this process)., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ripples are a typical form of neural activity in hippocampal neural networks associated with the replay of episodic memories during sleep as well as sleep-related plasticity and memory consolidation. The emergence of ripples has been observed both dependent as well as independent of input from other brain areas and often coincides with dendritic spikes. Yet, it is unclear how input-evoked and spontaneous ripples as well as dendritic excitability affect plasticity and consolidation. Here, we use mathematical modeling to compare these cases. We find that consolidation as well as the emergence of spontaneous ripples depends on a reliable propagation of activity in feed-forward structures which constitute memory representations. This propagation is facilitated by excitable dendrites, which entail that a few strong synapses are sufficient to trigger neuronal firing. In this situation, stimulation-evoked ripples lead to the potentiation of weak synapses within the feed-forward structure and, thus, to a consolidation of a more general sequence memory. However, spontaneous ripples that occur without stimulation, only consolidate a sparse backbone of the existing strong feed-forward structure. Based on this, we test a recently hypothesized scenario in which the excitability of dendrites is transiently enhanced after learning, and show that such a transient increase can strengthen, restructure and consolidate even weak hippocampal memories, which would be forgotten otherwise. Hence, a transient increase in dendritic excitability would indeed provide a mechanism for stabilizing memories., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jauch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Memory consolidation relies in part on the reactivation of previous experiences during sleep. The precise interplay of sleep-related oscillations (slow oscillations, spindles and ripples) is thought to coordinate the information flow between relevant brain areas, with ripples mediating memory reactivation. However, in humans empirical evidence for a role of ripples in memory reactivation is lacking. Here, we investigated the relevance of sleep oscillations and specifically ripples for memory reactivation during human sleep using targeted memory reactivation. Intracranial electrophysiology in epilepsy patients and scalp EEG in healthy participants revealed that elevated levels of slow oscillation - spindle activity coincided with the read-out of experimentally induced memory reactivation. Importantly, spindle-locked ripples recorded intracranially from the medial temporal lobe were found to be correlated with the identification of memory reactivation during non-rapid eye movement sleep. Our findings establish ripples as key-oscillation for sleep-related memory reactivation in humans and emphasize the importance of the coordinated interplay of the cardinal sleep oscillations., (© 2024. The Author(s).)

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well-established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within the BLA governs these modulatory effects. However, most current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a low-arousing, hippocampal-dependent task. Our experiments combined a weak object location task (OLT) version with subsequent mild predator odor exposure (POE). To investigate the role of endogenous NA in the BLA in memory modulation, a subset of the animals (Wistar rats) was treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected 90 min after drug infusion or after the OLT test, which was performed 24 h later. We used the obtained samples to estimate the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc)-two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE has the potential to become a valuable behavioral paradigm for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.

Memory reactivation during sleep is thought to facilitate memory consolidation. Most sleep reactivation research has examined how reactivation of specific facts, objects, and associations benefits their overall retention. However, our memories are not unitary, and not all features of a memory persist in tandem over time. Instead, our memories are transformed, with some features strengthened and others weakened. Does sleep reactivation drive memory transformation? We leveraged the Targeted Memory Reactivation technique in an object category learning paradigm to examine this question. Participants (20 female, 14 male) learned three categories of novel objects, where each object had unique, distinguishing features as well as features shared with other members of its category. We used a real-time EEG protocol to cue the reactivation of these objects during sleep at moments optimized to generate reactivation events. We found that reactivation improved memory for distinguishing features while worsening memory for shared features, suggesting a differentiation process. The results indicate that sleep reactivation does not act holistically on object memories, instead supporting a transformation where some features are enhanced over others., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Across animal species, dopamine-operated memory systems comprise anatomically segregated, functionally diverse subsystems. Although individual subsystems could operate independently to support distinct types of memory, the logical interplay between subsystems is expected to enable more complex memory processing by allowing existing memory to influence future learning. Recent comprehensive ultrastructural analysis of the Drosophila mushroom body revealed intricate networks interconnecting the dopamine subsystems-the mushroom body compartments. Here, we review the functions of some of these connections that are beginning to be understood. Memory consolidation is mediated by two different forms of network: A recurrent feedback loop within a compartment maintains sustained dopamine activity required for consolidation, whereas feed-forward connections across compartments allow short-term memory formation in one compartment to open the gate for long-term memory formation in another compartment. Extinction and reversal of aversive memory rely on a similar feed-forward circuit motif that signals omission of punishment as a reward, which triggers plasticity that counteracts the original aversive memory trace. Finally, indirect feed-forward connections from a long-term memory compartment to short-term memory compartments mediate higher-order conditioning. Collectively, these emerging studies indicate that feedback control and hierarchical connectivity allow the dopamine subsystems to work cooperatively to support diverse and complex forms of learning., (© 2024 Davidson and Hige; Published by Cold Spring Harbor Laboratory Press.)

A large body of evidence has shown that treatments that interfere with memory consolidation become ineffective when animals are subjected to an intense learning experience; this effect has been observed after systemic and local administration of amnestic drugs into several brain areas, including the striatum. However, the effects of amnestic treatments on the process of extinction after intense training have not been studied. Previous research demonstrated increased spinogenesis in the dorsomedial striatum, but not in the dorsolateral striatum after intense training, indicating that the dorsomedial striatum is involved in the protective effect of intense training. To investigate this issue, male Wistar rats, previously trained with low, moderate, or high levels of foot shock, were used to study the effect of tetrodotoxin inactivation of dorsomedial striatum on memory consolidation and subsequent extinction of inhibitory avoidance. Performance of the task was evaluated during seven extinction sessions. Tetrodotoxin produced a marked deficit of memory consolidation of inhibitory avoidance trained with low and moderate intensities of foot shock, but normal consolidation occurred when a relatively high foot shock was used. The protective effect of intense training was long-lasting, as evidenced by the high resistance to extinction exhibited throughout the extinction sessions. We discuss the possibility that increased dendritic spinogenesis in dorsomedial striatum may underly this protective effect, and how this mechanism may be related to the resilient memory typical of post-traumatic stress disorder (PTSD)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Martínez-Degollado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It has been well established that a consolidated memory can be updated during the plastic state induced by reactivation. This updating process opens the possibility to modify maladaptive memory. In the present study, we evaluated whether fear memory could be updated to less-aversive level by incorporating hedonic information during reactivation. Thus, male rats were fear conditioned and, during retrieval, a female was presented as a social rewarding stimulus. We found that memory reactivation with a female (but not a male) reduces fear expression within-session and in the test, without presenting reinstatement or spontaneous recovery. Interestingly, this intervention impaired extinction. Finally, we demonstrated that this emotional remodeling to eliminate fear expression requires the activation of dopamine and oxytocin receptors during retrieval. Hence, these results shed new lights on the memory updating process and suggests that the exposure to natural rewarding information such as a female during retrieval reduces a previously consolidated fear memory., (© 2024. The Author(s).)

Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales remains unclear. Here, we aimed to identify brain activity associated with retrieval of partly consolidated episodic memories that continued to be remembered in the future. Forty-nine younger (20 to 38 years; 25 females) and 43 older adults (60 to 80 years, 25 females) were scanned with functional magnetic resonance imaging during associative memory retrieval 12 h post-encoding. Twelve hours is sufficient to allow short-term synaptic consolidation as well as early post-encoding replay to initiate memory consolidation. Successful memory trials were classified into durable and transient source memories based on responses from a memory test ~6 d post-encoding. Results demonstrated that successful retrieval of future durable vs. transient memories was supported by increased activity in a medial prefrontal and ventral parietal area. Individual differences in activation as well as the subjective vividness of memories during encoding were positively related to individual differences in memory performance after 6 d. The results point to a unique and novel aspect of brain activity supporting long-term memory, in that activity during retrieval of memories even after 12 h of consolidation contains information about potential for long-term durability., (© The Author(s) 2024. Published by Oxford University Press.)

Navigation through space is based on memory representations of landmarks ('place') or movement sequences ('response'). Over time, memory representations transform through consolidation. However, it is unclear how the transformation affects place and response navigation in humans. In the present study, healthy adults navigated to target locations in a virtual maze. The preference for using place and response strategies and the ability to recall place and response memories were tested after a delay of one hour (n = 31), one day (n = 30), or two weeks (n = 32). The different delays captured early-phase synaptic changes, changes after one night of sleep, and long-delay changes due to the reorganization of navigation networks. Our results show that the relative contributions of place and response navigation changed as a function of time. After a short delay of up to one day, participants preferentially used a place strategy and exhibited a high degree of visual landmark exploration. After a longer delay of two weeks, place strategy use decreased significantly. Participants now equally relied on place and response strategy use and increasingly repeated previously taken paths. Further analyses indicate that response strategy use predominantly occurred as a compensatory strategy in the absence of sufficient place memory. Over time, place memory faded before response memory. We suggest that the observed shift from place to response navigation is context-dependent since detailed landmark information, which strongly relied on hippocampal function, decayed faster than sequence information, which required less detail and depended on extra-hippocampal areas. We conclude that changes in place and response navigation likely reflect the reorganization of navigation networks during systems consolidation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The benefits of physical exercise (PE) on memory consolidation have been well-documented in both healthy and memory-impaired animals. However, the underlying mechanisms through which PE exerts these effects are still unclear. In this study, we aimed to investigate the role of hippocampal protein synthesis in memory modulation by acute PE in rats. After novel object recognition (NOR) training, rats were subjected to a 30-min moderate-intensity acute PE on the treadmill, while control animals did not undergo any procedures. Using anisomycin (ANI) and rapamycin (RAPA), compounds that inhibit protein synthesis through different mechanisms, we manipulated protein synthesis in the CA1 region of the hippocampus to examine its contribution to memory consolidation. Memory was assessed on days 1, 7, and 14 post-training. Our results showed that inhibiting protein synthesis by ANI or RAPA impaired NOR memory consolidation in control animals. However, acute PE prevented this impairment without affecting memory persistence. We also evaluated brain-derived neurotrophic factor (BDNF) levels after acute PE at 0.5h, 2h, and 12h afterward and found no differences in levels compared to animals that did not engage in acute PE or were only habituated to the treadmill. Therefore, our findings suggest that acute PE could serve as a non-pharmacological intervention to enhance memory consolidation and prevent memory loss in conditions associated with hippocampal protein synthesis inhibition. This mechanism appears not to depend on BDNF synthesis in the early hours after exercise., Competing Interests: Declaration of competing interest The authors of the manuscript “ACUTE PHYSICAL EXERCISE PREVENTS MEMORY AMNESIA CAUSED BY PROTEIN SYNTHESIS INHIBITION IN RATS' HIPPOCAMPUS” submitted for publication in Neurochemistry International, declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)