Memory Consolidation Research Articles

Association of Sleep Spindle Rate With Memory Consolidation in Children With Rolandic Epilepsy.

Rolandic epilepsy (RE), the most common childhood focal epilepsy syndrome, is characterized by a transient period of sleep-activated epileptiform activity in the centrotemporal regions and variable cognitive deficits. Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in RE and related sleep-activated epileptic encephalopathies. To further evaluate the association between this electrographic biomarker and cognitive dysfunction in this common disease, we investigate whether children with RE have deficient sleep-dependent memory consolidation and whether impaired memory consolidation is associated with reduced sleep spindles in the centrotemporal regions. In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using an automated sleep spindle detector validated for use in children with and without epilepsy. Twenty-three children with RE (9 with active disease, 5F, age 6.9-12.8 years; 14 with resolved disease, 8F, age 8.8-17.8 years) and 19 age-matched and sex-matched controls (8F, age 6.9-18.7 years) were enrolled. Children with active epilepsy had decreased memory consolidation compared with control children (p = 0.001, mean percentage reduction 25.7%, 95% CI 10.3%-41.2%) and compared with children with resolved epilepsy (p = 0.007, mean percentage reduction 21.9%, 95% CI 6.2%-37.6%). Children with active epilepsy had decreased sleep spindle rates in the centrotemporal region compared with controls (p = 0.008, mean decrease 2.5 spindles per minute, 95% CI 0.7-4.4 spindles per minute). Spindle rate, but not spike rate or spike-wave index, correlated with sleep-dependent memory consolidation (p = 0.004, mean MST improvement of 3.9%, 95% CI 1.3%-6.4%, for each unit increase in spindles per minute). Children with RE have impaired sleep-dependent memory consolidation during the active period of disease that correlates with a deficit in the sleep spindle rate. This finding identifies a noninvasive biomarker to aid diagnosis and a potential etiologic mechanism to guide therapeutic discovery of cognitive dysfunction in RE and related sleep-activated epilepsy syndromes.

The molecular mechanism of nitric oxide in memory consolidation and its role in the pathogenesis of memory-related disorders.

Memory is a dynamic process of encoding, storing, and retrieving information. It includes sensory, short-term, and long-term memory, each with unique characteristics. Nitric oxide (NO) is a biological messenger synthesized on demand by neuronal nitric oxide synthase (nNOS) through a biochemical process initiated by glutamate binding to NMDA receptors, causing membrane depolarization and calcium influx. NO is known to regulate many signaling pathways including those related to memory consolidation. To throw light on the precise molecular mechanism of nitric oxide (NO) in memory consolidation and the possibility of targeting NO pathways as a therapeutic approach to scale down cognitive impairments. We conducted a search of the PubMed MEDLINE database, maintained by the US National Library of Medicine. The search strategy utilized Medical Subject Headings (MeSH) terms, including "nitric oxide and memory," "nitric oxide synthesis in the brain," "nitric oxide and Alzheimer's," "nitric oxide and Parkinson's," and "nitric oxide, neurodegenerative disorders, and psychiatric disorders." Additionally, relevant keywords such as "nitric oxide," "memory," and "cognitive disorders" were employed. We included the most recent preclinical and clinical studies pertinent to the review topic and limited the selection to articles published in English. NO exerts its role in memory consolidation by diffusing between neurons to promote synaptic plasticity, especially long-term potentiation (LTP). It acts as a retrograde messenger, neurotransmitter release modulator, and synaptic protein modifier. The dysregulation of NO balance in the brain can contribute to the pathogenesis of various neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and psychiatric disorders. The disturbance in NO signaling is strongly correlated with synaptic signaling dysfunction and oxidative stress. NO plays a fundamental role in memory consolidation, and its dysregulation contributes to cognitive impairment-a hallmark of numerous neurodegenerative and psychiatric disorders. Future research should aim to deepen our understanding of the mechanisms underlying NO's involvement in memory consolidation and to explore therapeutic strategies targeting the NO pathway to mitigate cognitive decline in affected individuals.

Sleep-driven prefrontal cortex coordinates temporal action and multimodal integration.

Cognitive processes such as action planning and decision-making require the integration of multiple sensory modalities in response to temporal cues, yet the underlying mechanism is not fully understood. Sleep has a crucial role for memory consolidation and promoting cognitive flexibility. Our aim is to identify the role of sleep in integrating different modalities to enhance cognitive flexibility and temporal task execution while identifying the specific brain regions that mediate this process. We have designed "Auditory-Gated Patience-to-Action" Task in which mice should process different auditory signals before action execution as well as analyzing the visual inputs for feedback of their action. Mice could learn the task rule and apply it only after sleeping period and could keep the performance constant across sessions. c-fos positive cells showed the involvement of prelimbic cortex (PrL) during task execution. Chemo-genetic inhibition verified that PrL is required for proper signal response and action timing. These findings emphasize that sleep and cortical activity are keys for cognitive flexibility in adapting to different modalities.

Coordinating the energetic strategy of glia and neurons for memory.

Memory consolidation requires rapid energy supply to neurons. In a recent study, Francés et al. revealed the signal by which a neuron commands glia to limit fatty acid synthesis in favor of metabolite export during memory formation in Drosophila melanogaster. This mechanism coordinates just-in-time glial energy delivery in response to dynamic neuronal needs.

The Histone Lysine Demethylase KDM7A Contributes to Reward Memory via Fscn1-Induced Synaptic Plasticity in the Medial Prefrontal Cortex.

Lysine demethylase 7A (KDM7A) catalyzes the removal of dimethylation from histone H3 lysine 9 and lysine 27, both of which are associated with transcription repression. Previous study indicates that Kdm7a mRNA in the medial prefrontal cortex (mPFC) increases after drug exposure, yet its role in drug-related behaviors is largely unknown. In a morphine-conditioned place preference (CPP) paradigm, these findings reveal a specific increase of Kdm7a expression in the mPFC 7 days after drug withdrawal. Subsequently, these results demonstrate that knockdown of Kdm7a in the mPFC do not affect the acquisition of morphine-induced CPP, but it attenuate memory consolidation. To further explore Kdm7a-mediated transcriptomic changes, this work employs Nanopore direct RNA sequencing. Transcriptome profiling unveils several gene expression alterations impacted by KDM7A, which are enriched in relevant neural function categories. Notably, this work identifies and validates fascin actin-bundling protein 1 (Fscn1) as a downstream molecular target. Knockdown of Fscn1 has a similar impact on CPP to Kdm7a, along with corresponding decrease of dendritic spine density and neuronal activity in the mPFC. Additionally, silencing Kdm7a decreases enrichment of H3K9me2 and H3K27me2 at the Fscn1 promoter region, suggesting that KDM7A may act as a crucial regulator of transcriptional responses to morphine-related reward memory via Fscn1.

Modulating Cognitive Function with Antihypertensive Medications: aComprehensive Systematic Review On FMRI Studies.

Hypertension (HTN) is aprevalent cardiovascular condition associated with cognitive impairments, including memory deficits and attention lapses. Understanding the neural mechanisms underlying HTN-related cognitive dysfunction is crucial for optimizing treatment strategies. Asystematic review was conducted to explore the impact of antihypertensive medications on cognition, focusing on memory, attention, and emotion processing using functional magnetic resonance imaging (fMRI). Searches were performed in PubMed and Scopus up to March10, 2024, with no language restrictions. Atotal of 108 articles were identified, of which 12systematic reviews and meta-analyses met the inclusion criteria. Included studies investigated various antihypertensive drugs, including losartan, propranolol, spironolactone, and telmisartan, and their effects on cognitive processes. Losartan improved negative memory encoding and facilitated fear extinction via hippocampal and prefrontal modulation. Propranolol disrupted fear reconsolidation and reduced emotional memory retrieval, affecting the amygdala and hippocampus. Spironolactone prevented stress-induced memory shifts in the amygdala. Findings indicated distinct impacts of these medications on memory encoding, fear extinction, and stress-induced memory modulation, as evidenced by alterations in neural activity patterns observed on fMRI. Antihypertensive medications, such as losartan and propranolol, demonstrate potential in modulating memory, fear-related memory reconsolidation, and stress-induced memory modulation, highlighting their therapeutic implications for conditions like posttraumatic stress disorder (PTSD) and anxiety disorders. This review underscores the importance of fMRI studies in elucidating the neural correlates of HTN-related cognitive impairments and optimizing treatment approaches.

Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action.

There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (N2O)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA glutamate receptors. A growing body of evidence suggests that subanaesthetic doses of N2O (50%) can interfere with the reconsolidation of maladaptive memories in healthy participants and across a range of disorders. Negative biases in memory play a key role in the onset, maintenance, and recurrence of depressive episodes, and the disruption of affective memory reconsolidation is one plausible mechanism through which N2O exerts its therapeutic effects. Understanding N2O's mechanisms of action may facilitate future treatment development in depression. In this narrative review, we introduce the evidence supporting an antidepressant profile of N2O and evaluate its clinical use compared to other treatments. With a focus on the specific memory processes that are thought to be disrupted in depression, we consider the effects of N2O on memory reconsolidation and propose a memory-based mechanism of N2O antidepressant action.

Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease.

Alzheimer's Disease (AD), a progressive and age-associated neurodegenerative disorder, is primarily characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. Despite advances in targeting Aβ-mediated neuronal damage with anti-Aβ antibodies, these treatments provide only symptomatic relief and fail to address the multifactorial pathology of the disease. This necessitates the exploration of novel therapeutic approaches and a deeper understanding of molecular signaling mechanisms underlying AD. Phosphodiesterases (PDEs), particularly Phosphodiesterase 4 (PDE4), play a pivotal role in regulating cyclic adenosine monophosphate (cAMP), a key molecule involved in memory consolidation and cognitive function. PDE4 inhibitors have demonstrated potential in enhancing memory and cognition in preclinical models of AD by modulating cAMP signaling. However, their clinical translation has been limited due to challenges such as adverse effects, narrow therapeutic windows, and low specificity in mechanism of action. This review bridges the gap between preclinical discoveries and clinical applications of PDE4 inhibitors in AD. It highlights preclinical evidence supporting the neuroprotective and anti-inflammatory effects of PDE4 inhibitors while addressing challenges in their clinical development, including issues of safety, efficacy, and disease-specific targeting. By integrating findings from both preclinical and clinical studies, we provide a comprehensive understanding of the therapeutic potential of PDE4 inhibitors in AD. Furthermore, this review outlines future research directions aimed at optimizing PDE4 inhibition strategies for AD treatment, offering a roadmap to translate foundational insights into clinical realities.

Impact of sleep quality on academic achievements of undergraduate medical students: a cross-sectional study from Saudi Arabia

BackgroundSleep is an active process that affects human health and quality of life. Sleep is essential for learning and memory consolidation. Good sleep is required for good academic performance. Sleep disorders are common among medical students, due to the high academic load, stressful life, and hectic schedule. Therefore, this study aims to assess sleep quality among medical students.MethodsA cross-sectional study was conducted among medical students at King Khalid University by using the Pittsburgh sleep quality index (PSQI) to assess sleep duration, sleep efficiency, sleep latency, and global PSQI score. Participants were enrolled from second to sixth year. Bivariate and multivariate logistic regression were used to predict factors related to poor sleep quality.ResultsOut of 514 medical students, 453 (88.1%) of students exhibited poor sleep quality. Fourth year students were less likely to have poor sleep quality (AOR, 0.381; CI, 0.158–0.934) p = 0.035 and students with regular sleep schedule were more likely to be good sleepers (AOR,0.349; CI, 0.129–0.940) p = 0.037. Additionally, students who had more than five courses per semester more frequently had daytime sleepiness p = 0.03. However, Insufficient sleep was not significantly affected by factors like gender, different age groups, number of courses per semester, daytime sleeping, and students with varying Grade Point Averages (GPA).ConclusionPoor sleep quality is common among medical students, which may affect academic performance and general health. It is essential to educate them about good sleep hygiene and time management skills.

Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders.

Xenon gas is considered to be a safe anesthetic and imaging agent. Research on its other potentially beneficial effects suggests that xenon may have broad efficacy for treating health disorders. A number of reviews on xenon applications have been published, but none have focused on substance use disorders. Accordingly, we review xenon effects and targets relevant to the treatment of substance use disorders, with a focus on opioid use disorder and alcohol use disorder. We report that xenon inhaled at subsedative concentrations inhibits conditioned memory reconsolidation and opioid withdrawal symptoms. We review work by others reporting on the antidepressant, anxiolytic, and analgesic properties of xenon, which could diminish negative affective states and pain. We discuss research supporting the possibility that xenon could prevent analgesic- or stress-induced opioid tolerance and, by so doing could reduce the risk of developing opioid use disorder. The rapid kinetics, favorable safety and side effect profiles, and multitargeting capability of xenon suggest that it could be used as an ambulatory on-demand treatment to rapidly attenuate maladaptive memory, physical and affective withdrawal symptoms, and pain drivers of substance use disorders when they occur. Xenon may also have human immunodeficiency virus and oncology applications because its effects relevant to substance use disorders could be exploited to target human immunodeficiency virus reservoirs, human immunodeficiency virus protein-induced abnormalities, and cancers. Although xenon is expensive, low concentrations exert beneficial effects, and gas separation, recovery, and recycling advancements will lower xenon costs, increasing the economic feasibility of its therapeutic use. More research is needed to better understand the remarkable repertoire of effects of xenon and its potential therapeutic applications.

Shaping the structural dynamics of motor learning through cueing during sleep.

Enhancing the retention of recent memory traces through sleep reactivation is possible via Targeted Memory Reactivation (TMR), involving cueing learned material during post-training sleep. Evidence indicates detectable short-term microstructural changes in the brain within an hour after motor sequence learning, and post-training sleep is believed to contribute to the consolidation of these motor memories, potentially leading to enduring microstructural changes. In this study, we explored how TMR during post-training sleep affects performance gains and delayed microstructural remodeling, using both standard Diffusion Tensor Imaging (DTI) and advanced Neurite Orientation Dispersion & Density Imaging (NODDI). Sixty healthy young adults participated in a five-day protocol, undergoing five Diffusion-Weighted Imaging (DWI) sessions, pre- and post-two motor sequence training sessions, and after a post-training night of either regular sleep (RS) or TMR. Results demonstrated rapid skill acquisition on Day 1, followed by performance stabilization on Day 2, and improvement on Day 5, in both RS and TMR groups. (Re)training induced widespread microstructural changes in motor-related areas, initially involving the hippocampus, followed by a delayed engagement of the caudate nucleus. Mean Diffusivity (MD) changes were accompanied by increased Neurite Density Index (NDI) in the putamen, suggesting increased neurite density, while Free Water Fraction (FWF) reduction indicated glial reorganization. TMR-related structural differences emerged in the dorsolateral prefrontal cortex (DLPFC) on Day 2 and the right cuneus on Day 5, suggesting unique sleep TMR-related neural reorganization patterns. Persistence of practice-related structural changes, although moderated over time, suggest a lasting neural network reorganization, partially mediated by sleep TMR.

Re-encountering the phobic cue within days after a reconsolidation intervention is crucial to observe a lasting fear reduction in spider phobia.

Memory reconsolidation interventions offer an exciting alternative to exposure treatment because they may target fear memories directly, thereby preventing relapse. A previous reconsolidation intervention for spider fear abruptly reduced avoidance behaviour, whereas changes in self-reported fear followed later. In this pre-registered placebo-controlled study, we first aimed to conceptually replicate these effects in spider phobia. Second, we investigated whether re-encountering the phobic cue after the reconsolidation intervention is necessary for changes in self-reported fear to occur. Third, we tested whether the window to trigger such changes is time limited. Individuals with spider phobia (N = 69) were randomized into three groups and underwent a memory reactivation procedure with a tarantula, followed immediately by propranolol (reconsolidation intervention) or placebo. One reconsolidation intervention group and the placebo group re-encountered spiders two days after treatment in behavioural approach tasks, whereas another reconsolidation intervention group re-encountered spiders after four weeks. Changes in spider avoidance behaviour and self-reported fear were followed for one year. In the short term, the reconsolidation intervention was not more effective than placebo: both conditions benefited from the intervention. In the long term, the reconsolidation intervention was more effective than placebo, but only when the phobic stimulus was re-encountered within days after treatment. Specifically, we found less tarantula avoidance behaviour and self-reported fear over the course of one year when spiders were re-encountered two days after the reconsolidation intervention, but not when the behavioural test was conducted four weeks after the intervention. These findings challenge the idea that a reconsolidation-inspired intervention alone is sufficient to treat clinical fears: Experiencing the behavioural change during the re-encounter within days after the reconsolidation window has closed seems crucial to observe a lasting fear reduction.

The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats.

The tachykinin substance P (SP) facilitates learning and memory processes after its central administration. Activation of its different receptive sites, neurokinin-1 receptors (NK1Rs), as well as NK2Rs and NK3Rs was shown to influence learning and memory. The basal ganglia have been confirmed to play an important role in the control of memory processes and spatial learning mechanisms, and as part of the basal ganglia, the globus pallidus (GP) may also be involved in this regulation. SP-immunoreactive fibers and terminals, as well as NK1Rs and NK3Rs, were shown to be present in the GP. The present study aimed to examine whether the SP administered into the GP can influence spatial memory consolidation in the Morris water maze (MWM). Therefore, male Wistar rats received a post-trial microinjection of 0.4 microliters of 10ng SP, 100ng SP, or vehicle solution. The possible involvement of pallidal NK1Rs and NK3Rs in the SP effects was also studied by applying WIN51708 for NK1R antagonism and SR142801 as a selective NK3R antagonist. Our results showed that the lower dose of SP significantly decreased escape latency on the second day compared to control animals, while the higher dose was ineffective. Prior treatment with the NK1R antagonist WIN51708 could not block, while the NK3R antagonist SR142801 inhibited the effects of SP on memory consolidation in the MWM. Our results are the first to demonstrate that SP improves consolidation of spatial memory in the GP, and this effect is mediated through NK3Rs but not NK1Rs.

Reactivation and consolidation of memory traces during post-encoding rest across the adult lifespan.

Episodic memory is a critical cognitive function that enables the encoding, storage, and retrieval of new information. Memory consolidation, a key stage of episodic memory, stabilizes this newly encoded information into long-lasting brain "storage." Studies using fMRI to investigate post-encoding awake rest holds promise to shed light on early, immediate consolidation mechanisms. Here, we review fMRI studies during episodic memory to document common methods to investigate post-encoding consolidation, such as multivoxel pattern analysis (MVPA) and functional connectivity, and the current state of the science in both healthy younger and older adults. In young adults, post-encoding reactivation of stimuli-specific neural patterns in the hippocampus and its connectivity with cortical and subcortical areas (e.g., visual-temporal cortex, medial prefrontal, and medial parietal cortex) correlate with subsequent memory performance. Conversely, studies in older adults highlight the importance of large-scale brain networks during post-encoding rest, particularly the default mode network (DMN). Alterations in connectivity between the DMN and task-positive networks may help older adults maintain episodic memory. Furthermore, non-invasive brain stimulation techniques can enhance these post-encoding consolidation processes and improve memory performance in both younger and older adults. Notably, a lack of studies has investigated post-encoding memory consolidation in neurodegenerative disorders. This review underscores the importance of understanding how post-encoding neural reactivation and connectivity evolve with age to partially explain age-related declines in episodic memory performance and how such declines can be restored.

Individualized temporal patterns drive human sleep spindle timing

Sleep spindles are cortical electrical oscillations considered critical for memory consolidation and sleep stability. The timing and pattern of sleep spindles are likely to be important in driving synaptic plasticity during sleep as well as preventing disruption of sleep by sensory and internal stimuli. However, the relative importance of factors such as sleep depth, cortical up/down-state, and temporal clustering in governing sleep spindle dynamics remains poorly understood. Here, we analyze sleep data from 1,025 participants, statistically modeling the simultaneous influences of multiple factors on moment-to-moment spindle production using a point process-generalized linear model framework. Results reveal fingerprint-like timing patterns, characterized by a refractory period followed by a period of increased spindle activity, which are highly individualized yet consistent night-to-night, with increased variability with age. Strikingly, short-term (<15 s) temporal patterns of past spindle history are the main determinant of spindle timing, accounting for over 70% of the statistical deviance-surpassing the contribution of factors such as cortical up/down-state (slow oscillation phase), sleep depth, and long-term history (15 to 90 s, including ~50 s infraslow activity). Short-term history has a statistically significant influence in over 98% of the population, suggesting it is a near-universal feature of spindle activity. Short-term history and slow oscillation phase exert independent effects on spindle timing. Our results establish a robust statistical framework to examine abnormalities in sleep spindle timing observed in neurological disorders and aging, as well as the relationship between individualized sleep spindle timing, cognition, and sleep stability.

DNA methylation, histone acetylation in the regulation of memory and its modulation during aging.

Memory formation is associated with constant modifications of neuronal networks and synaptic plasticity gene expression in response to different environmental stimuli and experiences. Dysregulation of synaptic plasticity gene expression affects memory during aging and neurodegenerative diseases. Covalent modifications such as methylation on DNA and acetylation on histones regulate the transcription of synaptic plasticity genes. Changes in these epigenetic marks correlated with alteration of synaptic plasticity gene expression and memory formation during aging. These epigenetic modifications, in turn, are regulated by physiology and metabolism. Steroid hormone estrogen and metabolites such as S-adenosyl methionine and acetyl CoA directly impact DNA and histones' methylation and acetylation levels. Thus, the decline of estrogen levels or imbalance of these metabolites affects gene expression and underlying brain functions. In the present review, we discussed the importance of DNA methylation and histone acetylation on chromatin modifications, regulation of synaptic plasticity gene expression and memory consolidation, and modulation of these epigenetic marks by epigenetic modifiers such as phytochemicals and vitamins. Further, understanding the molecular mechanisms that modulate these epigenetic modifications will help develop recovery approaches.

Patients with dementia with Lewy bodies display a signature alteration of their cognitive connectome

Cognition plays a central role in the diagnosis and characterization of dementia with Lewy bodies (DLB). However, the complex associations among cognitive deficits in different domains in DLB are largely unknown. To characterize these associations, we investigated and compared the cognitive connectome of DLB patients, healthy controls (HC), and Alzheimer’s disease patients (AD). We obtained data from the National Alzheimer’s Coordinating Center. We built cognitive connectomes for DLB (n = 104), HC (n = 3703), and AD (n = 1985) using correlations among 24 cognitive measures mapping multiple cognitive domains. Connectomes were compared using global and nodal graph measures of centrality, integration, and segregation. For global measures, DLB showed a higher global efficiency (integration) and lower transitivity (segregation) than HC and AD. For nodal measures, DLB showed higher global efficiency in most measures, higher participation (centrality) in free-recall memory, processing speed/attention, and executive measures, and lower local efficiency (segregation) than HC. Compared with AD, DLB showed lower nodal strength and local efficiency, especially in memory consolidation. The cognitive connectome of DLB shows a loss of segregation, leading to a loss of cognitive specialization. This study provides the data to advance the understanding of cognitive impairment and clinical phenotype in DLB, with implications for differential diagnosis.

Sleep disturbances and their correlation with memory impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment

Background Episodic memory impairment is the core clinical feature of patients with typical Alzheimer's disease (AD) at an early stage. Since sleep plays a very important role in memory consolidation, the relationship between memory impairment and sleep disorders in AD patients is worthy of investigation. Objective To investigate sleep disturbances and their correlations with memory impairment in patients with AD and amnestic mild cognitive impairment (aMCI). Methods Forty-three patients with AD, 43 patients with aMCI, and 43 cognitively unimpaired controls (CUCs) were recruited and subjected to memory assessment via the Hopkins Verbal Learning Test–Revised and objective sleep evaluation via polysomnography (PSG). Results The total sleep time and the percentages of nonrapid eye movement (NREM) sleep stage 3 (N3) and the rapid eye movement (REM) were lower, while the percentages of NREM sleep stage 2 (N2) were greater in the AD and aMCI groups than in the CUC group (all p &lt; 0.01). Compared with the CUC group, the AD group also presented a longer sleep latency and higher NREM sleep stage 1 (N1) percentage, apnea-hypopnea index (AHI), periodic limb movements during sleep index (PLMSI), and arousal index (AI). Both total learning scores and delayed recall scores were positively correlated with the N3 sleep percentage and negatively correlated with the AHI and PLMSI (all p &lt; 0.01). Recognition scores were positively correlated with the N3 sleep percentage and negatively correlated with the AI (all p &lt; 0.01). Conclusions Our results suggest that sleep disturbance is correlated with learning and memory disability in AD and aMCI patients. PSG is useful for screening and monitoring AD.

Parvalbumin interneurons in the anterior cingulate cortex exhibit distinct processing patterns for fear and memory in rats.

The anterior cingulate cortex is responsible for multiple cognitive functions like fear, pain management, decision-making, risk and reward assessment, and memory consolidation. However, its cell-type-specific functions are not clearly understood. To reveal the selective functional role of Parvalbumin-expressing GABAergic interneurons in the ACC, we knocked down (KD) the PV gene in-vivo in rats. Behavioral tests showed significantly improved spatial memory (p=0.01) in ACC-PV-KD rats compared to control and sham groups, whereas novel object recognition memory was reduced significantly (p=0.001). The PV knockdown group also showed a longer freezing duration (p=0.001) and considerably fewer freezing responses (p=0.005) in the fear conditioning chamber. Additionally, the PV knockdown rats spent significantly (p=0.006) more time in the periphery and less time in the center of the open field box, indicating anxiety-like behavior. In conclusion, Parvalbumin expressing interneurons in ACC are functionally diverse and critical for regulating fear response, recognition memory and spatial memory. Completely elucidating the underlying mechanism and circuitry will open up therapeutic choices for associated disorders.

Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5.

Stress can alter behavior and contributes to psychiatric disorders by regulating the expression of the GluA2 AMPA receptor subunit. We have previously shown in mice that exposure to predator odor stress elevates GluA2 transcription in cerebellar molecular layer interneurons (MLIs), and MLI activity is required for fear memory consolidation. Here, we identified the critical involvement of adenylyl cyclase 5, in both the stress-induced increase in GluA2 in MLIs and the enhancement of fear memory. We found that noradrenaline release during predator odor stress activates AC5 and downstream PKA-CREB signaling. This pathway interacts synergistically with α1-adrenergic receptors to promote synaptic GluA2 expression in MLIs. At a behavioral level, predator odor stress potentiates associative fear memory, and this is abolished in AC5 knockout mice, suggesting that AC5-dependent plasticity is required for enhanced memory formation. Therefore, AC5 is a promising pharmacological target for preventing stress-enhanced fear memory.