Review: seizure-related consolidation and the network theory of epilepsy.

Epilepsy is a complex, multifaceted disease that affects patients in several ways in addition to seizures, including psychological, social, and quality of life issues, but epilepsy is also known to interact with sleep. Seizures often occur at the boundary between sleep and wake, patients with epilepsy often experience disrupted sleep, and the rate of inter-ictal epileptiform discharges increases during non-REM sleep. The Network Theory of Epilepsy did not address a role for sleep, but recent emphasis on the interaction between epilepsy and sleep suggests that post-seizure sleep may also be involved in the process by which seizures arise and become more severe with time ("epileptogenesis") by co-opting processes related to the formation of long-term memories. While it is generally acknowledged that recurrent seizures arise from the aberrant function of neural circuits, it is possible that the progression of epilepsy is aided by normal, physiological function of neural circuits during sleep that are driven by pathological signals. Studies recording multiple, single neurons prior to spontaneous seizures have shown that neural assemblies activated prior to the start of seizures were reactivated during post-seizure sleep, similar to the reactivation of behavioral neural assemblies, which is thought to be involved in the formation of long-term memories, a process known as Memory Consolidation. The reactivation of seizure-related neural assemblies during sleep was thus described as being a component of Seizure-Related Consolidation (SRC). These results further suggest that SRC may viewed as a network-related aspect of epilepsy, even in those seizures that have anatomically restricted neuroanatomical origins. As suggested by the Network Theory of Epilepsy as a means of interfering with ictogenesis, therapies that interfered with SRC may provide some anti-epileptogenic therapeutic benefit, even if the interference targeted structures that were not involved originally in the seizure. Here, we show how the Network Theory of Epilepsy can be expanded to include neural plasticity mechanisms associated with learning by providing an overview of Memory Consolidation, the mechanisms thought to underlie MC, their relation to Seizure-Related Consolidation, and suggesting novel, anti-epileptogenic therapies targeting interference with network activation in epilepsy following seizures during post-seizure sleep.

Offline hippocampal reactivation during dentate spikes supports flexible memory.

Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the cornu ammonis (CA) region and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events for supporting this offline process. SWRs have been studied extensively, but the contribution of DSs remains unclear. By combining triple-ensemble (DG-CA3-CA1) recordings and closed-loop optogenetics in mice, we show that, like SWRs, DSs synchronize spiking across DG and CA principal cells to reactivate population-level patterns of neuronal coactivity expressed during prior waking experience. Notably, the population coactivity structure in DSs is more diverse and higher dimensional than that seen during SWRs. Importantly, suppressing DG granule cell spiking selectively during DSs impairs subsequent flexible memory performance during multi-object recognition tasks and associated hippocampal patterns of neuronal coactivity. We conclude that DSs constitute a second offline network event central to hippocampal population dynamics serving memory-guided behavior.

The effects of shared, depression-specific, and anxiety-specific internalizing symptoms on negative and neutral episodic memories following post-learning sleep.

Emotional memory bias is a common characteristic of internalizing symptomatology and is enhanced during sleep. The current study employs bifactor S-1 modeling to disentangle depression-specific anhedonia, anxiety-specific anxious arousal, and the common internalizing factor, general distress, and test whether these internalizing symptoms interact with sleep to influence memory for emotional and neutral information. Healthy adults (N = 281) encoded scenes featuring either negative objects (e.g., a vicious looking snake) or neutral objects (e.g., a chipmunk) placed on neutral backgrounds (e.g., an outdoor scene). After a 12-hour period of daytime wakefulness (n = 140) or nocturnal sleep (n = 141), participants judged whether objects and backgrounds were the same, similar, or new compared with what they viewed during encoding. Participants also completed the mini version of the Mood and Anxiety Symptom Questionnaire. Higher anxious arousal predicted worse memory across all stimuli features, but only after a day spent being awake-not following a night of sleep. No significant effects were found for general distress and anhedonia in either the sleep or wake condition. In this study, internalizing symptoms were not associated with enhanced emotional memory. Instead, memory performance specifically in individuals with higher anxious arousal was impaired overall, regardless of emotional valence, but this was only the case when the retention interval spanned wakefulness (i.e., not when it spanned sleep). This suggests that sleep may confer a protective effect on general memory impairments associated with anxiety.

Targeted memory reactivation to augment treatment in post-traumatic stress disorder.

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.

Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults.

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.

Distinct Neural Plasticity Enhancing Visual Perception.

The developed human brain shows remarkable plasticity following perceptual learning, resulting in improved visual sensitivity. However, such improvements commonly require extensive stimuli exposure. Here we show that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural mechanisms relative to standard repetition-based learning. Participants (n = 20, 12 women, 8 men) encoded a visual discrimination task, followed by brief memory reactivations of only five trials each performed on separate days, demonstrating improvements comparable with standard repetition-based learning (n = 20, 12 women, 8 men). Reactivation-induced learning engaged increased bilateral intraparietal sulcus (IPS) activity relative to repetition-based learning. Complementary evidence for differential learning processes was further provided by temporal-parietal resting functional connectivity changes, which correlated with behavioral improvements. The results suggest that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural processes, engaging higher-order control and attentional resources while leading to similar perceptual gains. These unique brain mechanisms underlying improved perceptual learning efficiency may have important implications for daily life and in clinical conditions requiring relearning following brain damage.

Similarity of brain activity patterns during learning and subsequent resting state predicts memory consolidation.

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.

Regulation of long-term memory by a few clock neurons in Drosophila.

Identification of the neural circuits in the brain regulating animal behavior and physiology is critical for understanding brain functions and is one of the most challenging goals in neuroscience research. The fruitfly Drosophila melanogaster has often been used to identify the neural circuits involved in the regulation of specific behaviors because of the many neurogenetic tools available to express target genes in particular neurons. Neurons controlling sexual behavior, feeding behavior, and circadian rhythms have been identified, and the number of neurons responsible for controlling these phenomena is small. The search for a few neurons controlling a specific behavior is an important first step to clarify the overall picture of the neural circuits regulating that behavior. We previously found that the clock gene period (per), which is essential for circadian rhythms in Drosophila, is also essential for long-term memory (LTM). We have also found that a very limited number of per-expressing clock neurons in the adult brain are required for the consolidation and maintenance of LTM. In this review, we focus on LTM in Drosophila, introduce the concept of LTM regulation by a few clock neurons that we have recently discovered, and discuss how a few clock neurons regulate Drosophila LTM.

Memory Consolidation and Sleep in Children With Epilepsy: A Systematic Review.

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.

Slow wave sleep is associated with forgetting in patients with temporal lobe epilepsy.

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.

EEG subject-dependent neurofeedback training selectively impairs declarative memories consolidation process.

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.

Effects of post-learning nap in the recognition memory for faces in habitual nappers.

This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d'). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (ß, Ohit/Ofalse alarm). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible.

Sleep oscillations related to memory consolidation during aromatases inhibitors for breast cancer.

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.

Memory's gatekeeper: The role of PFC in the encoding of congruent events.

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.

Effects of evening smartphone use on sleep and declarative memory consolidation in male adolescents and young adults.

Exposure to short-wavelength light before bedtime is known to disrupt nocturnal melatonin secretion and can impair subsequent sleep. However, while it has been demonstrated that older adults are less affected by short-wavelength light, there is limited research exploring differences between adolescents and young adults. Furthermore, it remains unclear whether the effects of evening short-wavelength light on sleep architecture extend to sleep-related processes, such as declarative memory consolidation. Here, we recorded polysomnography from 33 male adolescents (15.42 ± 0.97 years) and 35 male young adults (21.51 ± 2.06 years) in a within-subject design during three different nights to investigate the impact of reading for 90 min either on a smartphone with or without a blue-light filter or from a printed book. We measured subjective sleepiness, melatonin secretion, sleep physiology and sleep-dependent memory consolidation. While subjective sleepiness remained unaffected, we observed a significant melatonin attenuation effect in both age groups immediately after reading on the smartphone without a blue-light filter. Interestingly, adolescents fully recovered from the melatonin attenuation in the following 50 min before bedtime, whereas adults still, at bedtime, exhibited significantly reduced melatonin levels. Sleep-dependent memory consolidation and the coupling between sleep spindles and slow oscillations were not affected by short-wavelength light in both age groups. Nevertheless, adults showed a reduction in N3 sleep during the first night quarter. In summary, avoiding smartphone use in the last hour before bedtime is advisable for adolescents and young adults to prevent sleep disturbances. Our research empirically supports general sleep hygiene advice and can inform future recommendations regarding the use of smartphones and other screen-based devices before bedtime.

Impaired episodic verbal memory recall after 1 week and elevated forgetting in children after mild traumatic brain injury - results from a short-term longitudinal study.

Objective: There is preliminary evidence that children after traumatic brain injury (TBI) have accelerated long-term forgetting (ALF), i.e., an adequate learning and memory performance in standardized memory tests, but an excessive rate of forgetting over delays of days or weeks. The main aim of this study was to investigate episodic memory performance, including delayed retrieval 1 week after learning, in children after mild TBI (mTBI). Methods: This prospective study with two time-points (T1: 1 week after injury and T2: 3-6 months after injury), included data of 64 children after mTBI and 57 healthy control children aged between 8 and 16 years. We assessed episodic learning and memory using an auditory word learning test and compared executive functions (interference control, working memory, semantic fluency and flexibility) and divided attention between groups. We explored correlations between memory performance and executive functions. Furthermore, we examined predictive factors for delayed memory retrieval 1 week after learning as well as for forgetting over time. Results: Compared to healthy controls, patients showed an impaired delayed recall and recognition performance 3-6 months after injury. Executive functions, but not divided attention, were reduced in children after mTBI. Furthermore, parents rated episodic memory as impaired 3-6 months after injury. Additionally, verbal learning and group, but not executive functions, were predictive for delayed recall performance at both time-points, whereas forgetting was predicted by group. Discussion: Delayed recall and forgetting over time were significantly different between groups, both post-acutely and in the chronic phase after pediatric mTBI, even in a very mildly injured patient sample. Delayed memory performance should be included in clinical evaluations of episodic memory and further research is needed to understand the mechanisms of ALF.

Enhancing and advancing the understanding and study of dreaming and memory consolidation: Reflections, challenges, theoretical clarity, and methodological considerations.

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.

Predatory Odor Exposure as a Potential Paradigm for Studying Emotional Modulation of Memory Consolidation-The Role of the Noradrenergic Transmission in the Basolateral Amygdala.

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.

High frequency oscillations in human memory and cognition: a neurophysiological substrate of engrams?

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

Infralimbic activity during REM sleep facilitates fear extinction memory.

Rapid eye movement (REM) sleep is known to facilitate fear extinction and play a protective role against fearful memories.1,2 Consequently, disruption of REM sleep after a traumatic event may increase the risk for developing PTSD.3,4 However, the underlying mechanisms by which REM sleep promotes extinction of aversive memories remain largely unknown. The infralimbic cortex (IL) is a key brain structure for the consolidation of extinction memory.5 Using calcium imaging, we found in mice that most IL pyramidal neurons are intensively activated during REM sleep. Optogenetically suppressing the IL specifically during REM sleep within a 4-h window after auditory-cued fear conditioning impaired extinction memory consolidation. In contrast, REM-specific IL inhibition after extinction learning did not affect the extinction memory. Whole-cell patch-clamp recordings demonstrated that inactivating IL neurons during REM sleep depresses their excitability. Together, our findings suggest that REM sleep after fear conditioning facilitates fear extinction by enhancing IL excitability and highlight the importance of REM sleep in the aftermath of traumatic events for protecting against traumatic memories.