Memory Formation Research Articles

Movement boosts memory: Investigating the effects of acute exercise on episodic long-term memory

Long-term memory is important for cognitive health across the lifespan. Previously research has indicated that a bout of exercise improves memory retention for approximately one week; however, its prolonged effects are unknown. This study investigated the effects of acute moderate-intensity exercise on long-term memory for 11 months. Participants engaged in the exercise intervention and seated rest control condition, followed by a word encoding memory task. Word retention in the exercise intervention was better than in the control condition at 6- and 8-weeks post-encoding. These findings suggest that exercise before encoding enhances long-term episodic memory recall for at least eight weeks.

Natto-derived dipeptide Gln-Gln attenuates scopolamine-induced memory impairment by enhancing cholinergic function in mice

This study investigated the efficacy of natto in counteracting memory impairment induced by scopolamine in mice and identified promising peptides. The peptide fraction prepared from natto fermented for 18 h with Bacillus subtilis var. natto TTCC12 improved memory retention and upregulated hippocampal neuroprotective gene expression, including for choline acetyltransferase (ChAT) and brain-derived neurotrophic factor. Metabolomic analysis revealed that several dipeptides, such as Gln-Leu, Gln-Ile, Gln-Gln, and Ala-Tyr, increased in the blood 60 min after oral administration of the natto peptide fraction in rats. These dipeptides significantly attenuated scopolamine-induced memory impairment and increased brain acetylcholine (ACh) levels. Specifically, Gln-Gln exhibited a dose-dependent improvement by enhancing cholinergic function through increased levels of ACh and ChAT. However, an equimolar amount of Gln, as a free amino acid, showed no significant effects. Therefore, this study demonstrated the potential of natto and its constituents, particularly dipeptides Gln-Gln, in mitigating cognitive impairment.

Preparing future primary school teachers to solve the problem of historical education of primary schoolchildren with the main focus on the formation of historical memory: Methodological and tech-nological aspects

Introduction. The article deals with the problem of preparing future teachers for delivering historical education and the formation of historical memory in primary schoolchildren. The purpose of the article is to clarify methodological and technological aspects of preparing future primary school teachers to solve the problem of historical education of primary schoolchildren with the main focus on the formation of historical memory. Materials and Methods. The study follows the value-semantic approach. The research methods employed include the survey, the unfinished sentence method, statistical methods and content analysis. Results. The authors summarized the existing theoretical research on this problem, identified the level of future teachers’ awareness about the history of our country, justified the need to apply a value-semantic approach to the process of preparing students for delivering historical education in primary school with the main focus on the formation of historical memory, and proposed ways of preparing students for delivering historical education. Conclusions. The authors conclude that the preparation of future teachers for historical education with the main focus on the formation of historical memory among students should be carried out on the basis of a value-semantic approach. The basis of readiness for the implementation of this process is high level of teachers’ awareness about the history of our country, as well as their understanding and practical application of the mechanism of historical education in conjunction with the formation of historical memory.

The microglial innate immune receptor TREM2 participates in fear memory formation through excessive prelimbic cortical synaptic pruning

IntroductionFear memory formation has been implicated in fear- and stress-related psychiatric disorders, including post-traumatic stress disorder (PTSD) and phobias. Synapse deficiency and microglial activation are common among patients with PTSD, and induced in animal models of fear conditioning. Increasing studies now focus on explaining the specific mechanisms between microglia and synapse deficiency. Though newly-identified microglia regulator triggering receptor expressed on myeloid cells 2 (TREM2) plays a role in microglial phagocytic activity, its role in fear-formation remains unknown.MethodsWe successfully constructed a fear- formation model by foot-shock. Four days after foot-shock, microglial capacity of synaptic pruning was investigated via western blotting, immunofluorescence and Golgi-Cox staining. Prelimbic chemical deletion or microglia inhibition was performed to detect the role of microglia in synaptic loss and neuron activity. Finally, Trem2 knockout mice or wild-type mice with Trem2 siRNA injection were exposed to foot-shock to identify the involvement of TREM2 in fear memory formation.ResultsThe results herein indicate that the foot-shock protocol in male mice resulted in a fear formation model. Mechanistically, fear conditioning enhanced the microglial capacity for engulfing synapse materials, and led to glutamatergic neuron activation in the prelimbic cortex. Prelimbic chemical deletion or microglia inhibition improved fear memory formation. Further investigation demonstrated that TREM2 regulates microglial phagocytosis, enhancing synaptic pruning. Trem2 knockout mice showed remarkable reductions in prelimbic synaptic pruning and reduced neuron activation, with decreased fear memory formation.DiscussionOur cumulative results suggest that prelimbic TREM2-mediated excessive microglial synaptic pruning is involved in the fear memory formation process, leading to development of abnormal stress-related behavior.

Macroscopic observation of a first order one-dimensional swelling-deswelling transition in a nanolayered material

AbstractThe high purity and superior quality of the synthetic clay mineral fluorohectorite allows for studies of phenomena that are masked by imperfections and the inhomogeneous charge distribution in the case of natural clay minerals. We have exploited this opportunity offered by synthetic fluorohectorite and report here digital optical microscopy observations of salinity controlled macroscopic swelling and deswelling behavior of extra-large nanolamellar clay mineral particle accordions of various sizes. We find that clay particle accordions, immersed in a saline solution, at sufficiently high salinity, are in their crystalline swelling region, with only a few water layers hydrating the accordion interlayer nano-spaces, corresponding to an interlayer spacing of about 1.5 nm. Using a micropipette as a micro-tweezer and thereby transferring accordions carefully back and forth between high and low salinity solutions, we observe well defined macroscopic accordion transitions between the crystalline swelling regime and an osmotic swelling regime where the interlayer spacings reach tens of nanometers, calculated from accordion thicknesses measured by digital imaging. The transitions display a clear first order character as evidenced by threshold salinity levels for their abrupt onsets as well as clear hysteresis with retention of crystalline or osmotic state memory, as salinity is increased or lowered. The experimental observations are supported by a theoretical model of the accordion interlayer spacing based on a Donnan equilibrium originating from the salinity gradient between the embedding saline solution and the ionic strength in the clay interlayers in the osmotic swelling regime.

Spatially resolved transcriptomic signatures of hippocampal subregions and Arc-expressing ensembles in active place avoidance memory

The rodent hippocampus is a spatially organized neuronal network that supports the formation of spatial and episodic memories. We conducted bulk RNA sequencing and spatial transcriptomics experiments to measure gene expression changes in the dorsal hippocampus following the recall of active place avoidance (APA) memory. Through bulk RNA sequencing, we examined the gene expression changes following memory recall across the functionally distinct subregions of the dorsal hippocampus. We found that recall induced differentially expressed genes (DEGs) in the CA1 and CA3 hippocampal subregions were enriched with genes involved in synaptic transmission and synaptic plasticity, while DEGs in the dentate gyrus (DG) were enriched with genes involved in energy balance and ribosomal function. Through spatial transcriptomics, we examined gene expression changes following memory recall across an array of spots encompassing putative memory-associated neuronal ensembles marked by the expression of the IEGs Arc, Egr1, and c-Jun. Within samples from both trained and untrained mice, the subpopulations of spatial transcriptomic spots marked by these IEGs were transcriptomically and spatially distinct from one another. DEGs detected between Arc + and Arc− spots exclusively in the trained mouse were enriched in several memory-related gene ontology terms, including “regulation of synaptic plasticity” and “memory.” Our results suggest that APA memory recall is supported by regionalized transcriptomic profiles separating the CA1 and CA3 from the DG, transcriptionally and spatially distinct IEG expressing spatial transcriptomic spots, and biological processes related to synaptic plasticity as a defining the difference between Arc + and Arc− spatial transcriptomic spots.

Neuroplasticity Meets Artificial Intelligence: A Hippocampus-Inspired Approach to the Stability–Plasticity Dilemma

The stability–plasticity dilemma remains a critical challenge in developing artificial intelligence (AI) systems capable of continuous learning. This perspective paper presents a novel approach by drawing inspiration from the mammalian hippocampus–cortex system. We elucidate how this biological system’s ability to balance rapid learning with long-term memory retention can inspire novel AI architectures. Our analysis focuses on key mechanisms, including complementary learning systems and memory consolidation, with emphasis on recent discoveries about sharp-wave ripples and barrages of action potentials. We propose innovative AI designs incorporating dual learning rates, offline consolidation, and dynamic plasticity modulation. This interdisciplinary approach offers a framework for more adaptive AI systems while providing insights into biological learning. We present testable predictions and discuss potential implementations and implications of these biologically inspired principles. By bridging neuroscience and AI, our perspective aims to catalyze advancements in both fields, potentially revolutionizing AI capabilities while deepening our understanding of neural processes.

PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation.

Relevance-based selectivity and high energy cost are two distinct features of long-term memory (LTM) formation that warrant its default inhibition. Spaced repetition of learning is a highly conserved cognitive mechanism that can lift this inhibition. Here, we questioned how the spacing effect integrates experience selection and energy efficiency at the cellular and molecular levels. We showed in Drosophila that spaced training triggers LTM formation by extending over several hours an increased mitochondrial metabolic activity in neurons of the associative memory center, the mushroom bodies (MBs). We found that this effect is mediated by PKCδ, a member of the so-called 'novel PKC' family of enzymes, which uncovers the critical function of PKCδ in neurons as a regulator of mitochondrial metabolism for LTM. Additionally, PKCδ activation and translocation to mitochondria result from LTM-specific dopamine signaling on MB neurons. By bridging experience-dependent neuronal circuit activity with metabolic modulation of memory-encoding neurons, PKCδ signaling binds the cognitive and metabolic constraints underlying LTM formation into a unified gating mechanism.

PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation

Relevance-based selectivity and high energy cost are two distinct features of long-term memory (LTM) formation that warrant its default inhibition. Spaced repetition of learning is a highly conserved cognitive mechanism that can lift this inhibition. Here, we questioned how the spacing effect integrates experience selection and energy efficiency at the cellular and molecular levels. We showed in Drosophila that spaced training triggers LTM formation by extending over several hours an increased mitochondrial metabolic activity in neurons of the associative memory center, the mushroom bodies (MBs). We found that this effect is mediated by PKCδ, a member of the so-called ‘novel PKC’ family of enzymes, which uncovers the critical function of PKCδ in neurons as a regulator of mitochondrial metabolism for LTM. Additionally, PKCδ activation and translocation to mitochondria result from LTM-specific dopamine signaling on MB neurons. By bridging experience-dependent neuronal circuit activity with metabolic modulation of memory-encoding neurons, PKCδ signaling binds the cognitive and metabolic constraints underlying LTM formation into a unified gating mechanism.

The effects of varying negativity and presentation duration of images on formation of false memories

Studies about“False memory” are developing in the field of cognitive psychology. This study aims to investigate the interplay between presentation duration, negativity, and the presence of misinformation in the formation of false memories. Participants were exposed to slides of varying emotional valences (negative and neutral) and presentation durations (long and short), followed by questions containing either target or false options (either “critical lures” or “foil”. Confidence levels for each response were also recorded. The study found that subjects were more prone to false memories when presented with misinformation in the form of critical questions, especially when the slides were negatively valenced. Furthermore, confidence levels for artificially generated false memories were significantly higher in the long-duration group but lower in the short-duration group. These findings suggest that the presence of misinformation and the emotional valence of the stimuli significantly influence the formation of false memories.

Formation of historical memory of the first independence period in Latvia in the Perestroika years, 1987–1990

The author analyses the evolution of a new historical narrative in Latvia during the era of Perestroika, a period marked by the emergence of numerous public initiatives springing from political and social movements. One of the key initiatives was the restoration of the memory of ‘forgotten pages of history’, namely events and individuals who had been erased from the historical record in the Soviet Union for ideological reasons. Given that the restoration of state sovereignty was a central objective of this period, the “revival” of commemorative dates related to the history of the Republic of Latvia’s first independence (1918–1940) was a logical consequence of the search for one’s roots. A number of historical events were not only integrated into the collective memory but also referenced in political documents designed to reinstate national sovereignty. One of the primary objectives of this process was to construct a new historical narrative that would assert continuity and legal identity between the Republic of Latvia of the interwar period and the one that emerged in the late Soviet era, seeking to secede from the USSR and regain its lost independence. The formulation of the doctrine of national continuity entailed, on the one hand, the pursuit of reference points that would serve as the basis for a new state and national identity, and, on the other hand, encompassed a public discourse on the “black pages” of history, reflecting the aspiration to overcome the challenging historical legacy associated with the loss of independence in 1940 and to establish a framework for legitimate international relations.

Reinforcement learning when your life depends on it: A neuro-economic theory of learning.

Synaptic plasticity enables animals to adapt to their environment, but memory formation can require a substantial amount of metabolic energy, potentially impairing survival. Hence, a neuro-economic dilemma arises whether learning is a profitable investment or not, and the brain must therefore judiciously regulate learning. Indeed, in experiments it was observed that during starvation, Drosophila suppress formation of energy-intensive aversive memories. Here we include energy considerations in a reinforcement learning framework. Simulated flies learned to avoid noxious stimuli through synaptic plasticity in either the energy expensive long-term memory (LTM) pathway, or the decaying anesthesia-resistant memory (ARM) pathway. The objective of the flies is to maximize their lifespan, which is calculated with a hazard function. We find that strategies that switch between the LTM and ARM pathways, based on energy reserve and reward prediction error, prolong lifespan. Our study highlights the significance of energy-regulation of memory pathways and dopaminergic control for adaptive learning and survival. It might also benefit engineering applications of reinforcement learning under resources constraints.

Cognitive Mechanisms of Graffiti: Compression, Defocusing, and Focusing

This study aims to identify the predominant cognitive mechanisms underlying graffiti. The analysis is based on photographs of over 2000 instances of urban graphic defacement (i.e., graffiti) documented in major cities across Russia, including Yekaterinburg, Moscow, Saint Petersburg, and Nizhny Novgorod. Utilizing content analysis and expert evaluation methods, the research delineates three key cognitive mechanisms that contribute to the semantic unity of graffiti. The first mechanism, compression, manifests in graphic defacements through linguistic play or the transmission of discursive texts. The second mechanism, defocusing, is linguistically actualized through the technique of absurdity (everyday anchors of illogicality) and the activation of the emotion of surprise. It is noted that surprise elicits various reactions from the audience — such as loss of control, bewilderment, and uncertainty — which subsequently leads to prolonged retention in memory of the meanings embedded in the respective graffiti against a backdrop of vivid and atypical psycho-emotional states. The third mechanism, focusing, is linguistically embodied in philosophical texts.

Brief disruption of activity in a subset of dopaminergic neurons during consolidation impairs long-term memory by fragmenting sleep.

Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) are involved in memory processing at multiple stages. Here, using both male and female flies, Drosophila melanogaster , we show that, during the first few hours of memory consolidation, disruption of basal activity of a small subset of protocerebral anterior medial DANs (PAM-DANs), by either brief activation or inhibition of the two dorsal posterior medial (DPM) neurons, impairs 24 h LTM. Interestingly, these brief changes in activity using female flies result in sleep loss and fragmentation, especially at night. Pharmacological rescue of sleep after manipulation restores LTM. A specific subset of PAM-DANs (PAM-α1) that synapse onto DPM neurons specify the microcircuit that links sleep and memory. PAM-DANs, including PAM-α1, form functional synapses onto DPM mainly via multiple dopamine receptor subtypes. This PAM-α1 to DPM microcircuit exhibits a synchronized, transient, post-training increase in activity during the critical memory consolidation window, suggesting an effect of this microcircuit on maintaining the sleep necessary for LTM consolidation. Our results provide a new cellular and circuit basis for the complex relationship between sleep and memory.

Decoding episodic autobiographical memory in naturalistic virtual reality

Episodic autobiographical memory (EAM) is a long-term memory system of personally experienced events with their context – what, where, when – and subjective elements, e.g., emotions, thoughts, or self-reference. EAM formation has rarely been studied in a controlled, real-life-like paradigm, and there is no predictive model of long-term retrieval from self-rated subjective experience at encoding. The present longitudinal study, with three surprise free recall memory tests immediately, one-week and one-month after encoding, investigated incidental encoding of EAM in an immersive virtual environment where 30 participants either interacted with or observed specific events of varying emotional valences with simultaneous physiological recordings. The predictive analyses highlight the temporal dynamics of the predictors of EAM from subjective ratings at encoding: common characteristics related to sense of remembering and infrequency of real-life encounter of the event were identified over time, but different variables become relevant at different time points, such as the emotion and mental imagery or prospective aspects. This dynamic and time-dependent role of memory predictors challenges traditional views of a uniform influence of encoding factors over time. Current evidence for the multiphasic nature of memory formation points to the role of different mechanisms at play during encoding but also consolidation and subsequent retrieval.

How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.

Emerging many-to-one weighted mapping in hippocampus-amygdala network underlies memory formation

Memories are crucial for daily life, yet the network-level organizing principles governing neural representations of experiences remain unknown. Employing dual-site in vivo recording in freely behaving male mice, here we show that hippocampal dorsal CA1 (dCA1) and basolateral amygdala (BLA) utilize distinct coding strategies for novel experiences. A small assembly of BLA neurons emerged active during memory acquisition and persisted through consolidation, whereas most dCA1 neurons were engaged in both processes. Machine learning decoding revealed that dCA1 population spikes predicted BLA assembly firing rate, suggesting that most dCA1 neurons concurrently index an episodic event by rapidly establishing weighted communication with a specific BLA assembly – a process we term “many-to-one weighted mapping.” We also found that dCA1 reactivations preceded BLA assembly activity preferably during elongated and enlarged dCA1 ripples. Using a closed-loop strategy, we demonstrated that suppressing BLA activity after large dCA1 ripples impaired memory. These findings highlight a many-to-one weighted mapping mechanism underlying both the acquisition and consolidation of new memories.

β-Amyloid impairs Proteasome structure and function. Proteasome activation mitigates amyloid induced toxicity and cognitive deficits.

Alzheimer's Disease (AD) is the leading cause of dementia globally, affecting around 50 million people and marked by cognitive decline and the accumulation of β-amyloid plaques and hyperphosphorylated tau. The limited treatment options and numerous failed clinical trials targeting β-amyloid (Aβ) highlight the need for novel approaches. Lowered proteasome activity is a consistent feature in AD, particularly in the hippocampus. Impaired proteasome function in AD is hypothesized to stem from direct inhibition by β-amyloid or hyperphosphorylated tau, disrupting critical neuronal processes such as memory formation and synaptic plasticity. This study tests the hypothesis that AD related deficits are driven in part by impaired proteasome function as a consequence of inhibition by Aβ. We evaluated how proteasome function is modulated by Aβ and the capacity of two proteasome-activating compounds, TAT1-8,9-TOD and TAT1-DEN to rescue Aβ-induced impairment in vitro, as well as survival deficits in cell culture and Aβ-induced cognitive deficits in Drosophila and mouse models. Our study demonstrates that oligomeric β-amyloid binds to the 20S proteasome and impairs its activity and conformational stability. The oligomers also destabilize the 26S proteasome to release the free 20S proteasome. Treatment with proteasome activators TAT1-8,9TOD and TAT1-DEN rescue the 20S proteasome function and reduces cell death caused by Aβ42 toxicity in SK-N-SH cells. In Drosophila models overexpressing Aβ42, oral administration of proteasome agonists delayed mortality and restored cognitive function. Chronic treatment with TAT1-DEN protected against deficits in working memory caused by Aβ42 in mice and in hAPP(J20) mice with established deficits, acute TAT1-DEN treatment significantly improved spatial learning, with treated mice performing comparably to controls. Aβ has dual impacts on 20S and 26S proteasome function and stability. Proteasome activation using TAT1-8,9TOD and TAT1-DEN shows promise in mitigating AD-like deficits by protecting against amyloid toxicity and enhancing proteasome function. These findings suggest that targeting proteasome activity could be a viable therapeutic approach for AD, warranting further investigation into the broader impacts of proteasome modulation on AD pathology.

Isolated theta waves originating from the midline thalamus trigger memory reactivation during NREM sleep in mice

During non-rapid eye movement (NREM) sleep, neural ensembles in the entorhinal-hippocampal circuit responsible for encoding recent memories undergo reactivation to facilitate the process of memory consolidation. This reactivation is widely acknowledged as pivotal for the formation of stable memory and its impairment is closely associated with memory dysfunction. To date, the neural mechanisms driving the reactivation of neural ensembles during NREM sleep remain poorly understood. Here, we show that the neural ensembles in the medial entorhinal cortex (MEC) that encode spatial experiences exhibit reactivation during NREM sleep. Notably, this reactivation consistently coincides with isolated theta waves. In addition, we found that the nucleus reuniens (RE) in the midline thalamus exhibits typical theta waves during NREM sleep, which are highly synchronized with those occurring in the MEC in male mice. Closed-loop optogenetic inhibition of the RE-MEC pathway specifically suppressed these isolated theta waves, resulting in impaired reactivation and compromised memory consolidation following a spatial memory task in male mice. The findings suggest that theta waves originating from the ventral midline thalamus play a role in initiating memory reactivation and consolidation during sleep.

Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.

Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor.