Making memories.

The neurotransmitter dopamine helps form long-term memories by increasing the production of proteins through a unique signaling pathway.

Synaptic weight dynamics underlying memory consolidation: Implications for learning rules, circuit organization, and circuit function.

Systems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area. We show that the synaptic dynamics of the circuit during consolidation of an analog memory can be understood as a temporal integration process, by which transient changes in activity driven by plasticity in the early-learning area are accumulated into persistent synaptic changes at the late-learning site. This simple principle naturally leads to a speed-accuracy tradeoff in systems consolidation and provides insight into how the circuit mitigates the stability-plasticity dilemma of storing new memories while preserving core features of older ones. Furthermore, it imposes two constraints on the circuit. First, the plasticity rule at the late-learning site must stably support a continuum of possible outputs for a given input. We show that this is readily achieved by heterosynaptic but not standard Hebbian rules. Second, to turn off the consolidation process and prevent erroneous changes at the late-learning site, neural activity in the early-learning area must be reset to its baseline activity. We provide two biologically plausible implementations for this reset that propose functional roles in stabilizing consolidation for core elements of the cerebellar circuit.

Socialization causes long-lasting behavioral changes.

In modern human societies, social isolation acts as a negative factor for health and life quality. On the other hand, social interaction also has profound effects on animal and human, impacting aggressiveness, feeding and sleep, among many other behaviors. Here, we observe that in the fly Drosophila melanogaster these behavioral changes long-last even after social interaction has ceased, suggesting that the socialization experience triggers behavioral plasticity. These modified behaviors maintain similar levels for 24 h and persist up to 72 h, although showing a progressive decay. We also find that impairing long-term memory mechanisms either genetically or by anesthesia abolishes the expected behavioral changes in response to social interaction. Furthermore, we show that socialization increases CREB-dependent neuronal activity and synaptic plasticity in the mushroom body, the main insect memory center analogous to mammalian hippocampus. We propose that social interaction triggers socialization awareness, understood as long-lasting changes in behavior caused by experience with mechanistic similarities to long-term memory formation.

Artificial olfactory memory system based on conductive metal-organic frameworks.

The olfactory system can generate unique sensory memories of various odorous molecules, guiding emotional and cognitive decisions. However, most existing electronic noses remain constrained to momentary concentration, failing to trigger specific memories for different smells. Here, we report an artificial olfactory memory system utilizing conductive metal-organic frameworks (Ce-HHTP) that integrates sensing and memory and exhibits short- and long-term memory responses to alcohols and aldehydes. Experiments and theoretical calculations show that distinct memories are derived from the specific combinations of Ce-HHTP with O atoms in different guest. An unmanned aircraft equipped with this system realized the sensory memories in established areas. Moreover, the fusion of portable detection boxes and wearable flexible electrodes demonstrated the immense potential in off-site pollution monitoring and health management. This work represents an artificial olfactory memory system with two specific sensory memories under simultaneous conditions, laying the foundation for bionic design with qualities of human olfactory memory.

Measuring the Effects of Cognitive Capacity on Sentence Comprehension: Evidence From Elementary School-Age Children.

PURPOSE: Our aim was to (a) develop a sentence comprehension measure that distinguished between cognitive capacity and syntactic knowledge in school-age children and (b) examine the relationship between comprehension performance and cognitive variables (working memory capacity and retrieval from long-term memory). METHOD: We developed and administered a picture selection sentence comprehension task to 122 school-age children representing varied cognitive abilities. We evaluated comprehension accuracy and response time in two syntactically identical conditions but with different cognitive demands incorporated in picture foils-one with low demand using superfluous adjectives and another with high demand using contrastive adjectives. Children also completed tasks measuring working memory capacity and long-term memory retrieval. RESULTS: Comprehension accuracy was significantly lower, and response times were longer in the high-cognitive demand condition compared to the low-demand condition. Errors frequently involved incorrect attribute selection in the high-demand condition that included contrastive adjectives in picture foils, while reversal errors prevailed in the low-demand condition, which included superfluous adjectives. Accuracy correlated positively with the memory variables. Hierarchical regression analysis showed that after adjusting for comprehension in the low-cognitive demand condition (38.60% variance), memory variables accounted for 4.50% additional variance in the high-demand condition with only working memory capacity as the unique predictor. CONCLUSIONS: The significant role of working memory capacity in comprehending sentences with high cognitive demand indicated the recruitment of active attention and verbal rehearsal. Data support the newly developed measure's potential for assessing cognitive skills integral to sentence comprehension in school-age children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26767063.

Perceptual comparisons induce lasting and generalizing changes to face memory reports.

Humans are often tasked to remember new faces so that they can recognize the faces later in time. Previous studies found that memory reports for basic visual features (e.g., colors and shapes) are susceptible to systematic distortions as a result of comparison with new visual input, especially when the input is perceived as similar to the memory. The current study tested whether this similarity-induced memory bias (SIMB) would also occur with more complex face stimuli. The results showed that faces that are just perceptually encoded into visual working memory as well as retrieved from visual long-term memory are also susceptible to SIMB. Furthermore, once induced, SIMB persisted over time across cues through which the face memory was accessed for memory report. These results demonstrate the generalizability of SIMB to more complex and practically relevant stimuli, and thus, suggest potential real-world implications.

Long-term memory in wild falcons.

Long-term memory - information retention over long timescales - can allow animals to retain foraging skills and efficiently respond to seasonally available resources and changing environments1. Most long-term memory research is with captive species, focusing on spatial, individual or object recognition, with less known about wild species and the retention of motor task abilities, as in the case of complex foraging skills2,3. We have examined whether wild striated caracaras (Phalcoboenus australis), recently shown to rapidly and flexibly innovate with an eight-task puzzle box4, retain task memories one year later. We found that, despite no reinforcement, caracaras repeated motor techniques that led to their most recent success on tasks the year prior, solving nearly twice as fast as a naïve control group and four times faster than when naïve. Our results suggest long-term memory may be important for non-migratory opportunistic generalists, particularly in remote island environments with seasonally available resources, and further highlight how striated caracaras are promising candidates for avian cognitive studies.

EphrinB2 in excitatory neurons and astrocytes in the basolateral amygdala controls long-term fear memory formation.

EphrinB2 regulates synaptic transmission and morphology however its role in memory formation is unknown. Here we show that deleting ephrinB2 from excitatory neurons in the basolateral amygdala (BLA) of male mice impairs long-term (LTM), but not short-term (STM), fear memory formation. Deleting ephrinB2 from astrocytes in the BLA impairs fear LTM but not STM. Removing ephrinB2 from astrocytes in the BLA reduces the level of the excitatory amino acid transporter 1 (EAAT1) in these cells. Inhibiting EAAT1 activity in the BLA during fear conditioning, by its specific inhibitor UCPH-101, impairs fear LTM showing that EAAT1 in the BLA is needed for fear LTM formation. The administration of ephrinB2 into the BLA during fear conditioning training enhances fear LTM. Moreover, ephrinB2 increases the ability of fear conditioning to activate cells in the BLA as detected by c-Fos labeling. EphrinB2 therefore determines the threshold for fear memory formation. In contrast to mature neurons, we show that ephrinB2 in neural stem cells (NSCs) is not needed for fear LTM. Our study shows that ephrinB2 in the BLA determines the strength of long-term memory consolidation.

Effects of Context Changes on Memory Reactivation.

While the influence of context on long-term memory (LTM) is well documented, its effects on the interaction between working memory (WM) and LTM remain less understood. In this study, we explored these interactions using a delayed match-to-sample task, where participants (6 males, 16 females) encountered the same target object across six consecutive trials, facilitating the transition from WM to LTM. During half of these target repetitions, the background color changed. We measured the WM storage of the target using the contralateral delay activity in electroencephalography. Our results reveal that task-irrelevant context changes trigger the reactivation of long-term memories in WM. This reactivation may be attributed to content-context binding in WM and hippocampal pattern separation.

The weekend warrior effect: Consistent intermittent exercise induces persistent cognitive benefits.

Exercise provides a range of cognitive benefits, including improved memory performance. Previously, we demonstrated that 14 days of continuous voluntary wheel-running exercise enables learning in a hippocampus-dependent Object Location Memory (OLM) task under insufficient, subthreshold training conditions in adult mice. Whether similar exercise benefits can be obtained from consistent intermittent exercise as continuous exercise is unknown. Here, we examine whether intermittent exercise (the weekend warrior effect: 2 days of exercise a week for 7 weeks) displays similar or distinct cognitive benefits as previously examined with 14 days of continuous exercise. We find that both continuous and intermittent exercise parameters similarly enable hippocampus-dependent OLM compared to the 2-day exercise control group. Mice receiving intermittent exercise maintained cognitive benefits following a 7-day sedentary delay, whereas mice that underwent 14 continuous days of exercise showed diminished cognitive benefits as previously reported. Further, compared to continuous exercise, intermittent exercise mice exhibited persistently elevated levels of the genes Acvr1c and Bdnf which we know to be critically involved in hippocampus-dependent long-term memory in the dorsal hippocampus. Together findings suggest that consistent intermittent exercise persistently enables hippocampal-dependent long-term memory. Understanding the optimal parameters for persistent cognitive function and the mechanisms mediating persistent effects will aid in therapeutic pursuits investigating the mitigation of cognitive ailments.

The effect of miR­155­5p on long­term memory of sleep­deprived mice through the BDNF/NF­κB pathway.

Sleep deprivation (SD) is a prevalent sleep issue in modern society that significantly impairs neurological function and quality of life in affected individuals. This study seeks to investigate the involvement of the miR­155­5p/BDNF axis in SD mice, aiming to establish a theoretical foundation for potential treatment strategies. Male C57BL/6 mice were utilized in the construction of a SD model using the flower pot technique. HT22 cells were selected for cellular experiments. The Morris water maze was employed to assess the learning and memory capabilities of the mice. HE staining was utilized to observe pathological changes in hippocampal tissue. Levels of IL­1ß, IL­6, and TNF­α were analyzed using ELISA. The expression level of miR­155­5p was quantified via RT­qPCR. The binding between miR­155­5p and brain­derived neurotrophic factor (BDNF) was confirmed through a dual­luciferase reporter assay. Apoptosis of hippocampal neurons was assessed using TUNEL. Western blot analysis was conducted to evaluate the expression levels of BDNF, p65, and p­p65. The Morris water maze test revealed that the mice exhibited prolonged escape latency, decreased swimming velocity, and reduced time spent in the target platform quadrant, which are indicative of a successful construction of the SD model. The observed cognitive deficits in the mice were associated with SD­induced damage to the hippocampal tissue, leading to increased levels of miR­155­5p and decreased levels of BDNF. miR­155­5p was found to directly bind to BDNF, thereby suppressing its mRNA and protein expression. The upregulation of BDNF effectively mitigated hippocampal damage by attenuating cell apoptosis and reducing inflammation levels in SD mice. Additionally, the BDNF/NF­κB pathway was found to be suppressed in SD mice through the downregulation of miR­155­5p. Therefore, the silencing of miR­155­5p inhibited the activation of the NF­κB pathway by upregulating BDNF, which improved long­term memory and reduced neuronal damage in SD mice.

How to reduce fear in a snail: Take an aspirin, call me in the morning.

Aspirin (Acetylsalicylic acid, ASA), one of the widely used non-steroid anti-inflammatory drugs can easily end up in sewage effluents and thus it becomes necessary to investigate the effects of aspirin on behaviour of aquatic organisms. Previous studies in mammals have shown ASA to alter fear and anxiety-like behaviours. In the great pond snail Lymnaea stagnalis, ASA has been shown to block a 'sickness state' induced by lipopolysaccharide injection which upregulates immune and stress-related genes thus altering behavioural responses. In Lymnaea, eliciting physiological stress may enhance memory formation or block its retrieval depending on the stimulus type and intensity. Here we examine whether ASA will alter two forms of associative-learning memory in crayfish predator-experienced Lymnaea when ASA exposure accompanies predator-cue-induced stress during the learning procedure. The two trainings procedures are: 1) operant conditioning of aerial respiration; and 2) a higher form of learning, called configural learning, which here is dependent on evoking a fear response. We show here that ASA alone does not alter homeostatic aerial respiration, feeding behaviour or long-term memory (LTM) formation of operantly conditioned aerial respiration. However, ASA blocked the enhancement of LTM formation normally elicited by training snails in predator cue. ASA also blocked configural learning, which makes use of the fear response elicited by the predator cue. Thus, ASA alters how Lymnaea responds cognitively to predator detection.

Temporal gamma tACS and auditory stimulation affect verbal memory in healthy adults.

Research suggests a potential of gamma oscillation entrainment for enhancing memory in Alzheimer's disease and healthy subjects. Gamma entrainment can be accomplished with oscillatory electrical, but also sensory stimulation. However, comparative studies between sensory stimulation and transcranial alternating current stimulation (tACS) effects on memory processes are lacking. This study examined the effects of rhythmic gamma auditory stimulation (rAS) and temporal gamma-tACS on verbal long-term memory (LTM) and working memory (WM) in 74 healthy individuals. Participants were assigned to two groups according to the stimulation techniques (rAS or tACS). Memory was assessed in three experimental blocks, in which each participant was administered with control, 40, and 60 Hz stimulation in counterbalanced order. All interventions were well-tolerated, and participants reported mostly comparable side effects between real stimulation (40 and 60 Hz) and the control condition. LTM immediate and delayed recall remained unaffected by stimulations, while immediate recall intrusions decreased during 60 Hz stimulation. Notably, 40 Hz interventions improved WM compared to control stimulations. These results highlight the potential of 60 and 40 Hz temporal cortex stimulation for reducing immediate LTM recall intrusions and improving WM performance, respectively, probably due to the entrainment of specific gamma oscillations in the auditory cortex. The results also shed light on the comparative effects of these neuromodulation tools on memory functions, and their potential applications for cognitive enhancement and in clinical trials.

Hippocampal hub failure is linked to long-term memory impairment in anti-NMDA-receptor encephalitis: insights from structural connectome graph theoretical network analysis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis. METHODS: Structural networks from 61 NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and 61 age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically constrained tractography and volumetry of a selection of subcortical and white matter brain volumes was performed. We calculated global, modular, and nodal graph measures with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were investigated regarding their potential association with clinical course, disease severity, and cognitive outcome. RESULTS: Patients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p = 0.049; right: p = 0.013) and increased node strength of right precuneus (p = 0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p = 0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p = 0.021). We found decreased left (p = 0.013) and right (p = 0.001) hippocampal volumes that were associated with hippocampal node strength (left p = 0.009; right p < 0.001). CONCLUSIONS: Focal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.

Rhythmic Temporal Cues Coordinate Cross-frequency Phase-amplitude Coupling during Memory Encoding.

Accumulating evidence suggests that rhythmic temporal cues in the environment influence the encoding of information into long-term memory. Here, we test the hypothesis that these mnemonic effects of rhythm reflect the coupling of high-frequency (gamma) oscillations to entrained lower-frequency oscillations synchronized to the beat of the rhythm. In Study 1, we first test this hypothesis in the context of global effects of rhythm on memory, when memory is superior for visual stimuli presented in rhythmic compared with arrhythmic patterns at encoding [Jones, A., & Ward, E. V. Rhythmic temporal structure at encoding enhances recognition memory, Journal of Cognitive Neuroscience, 31, 1549-1562, 2019]. We found that rhythmic presentation of visual stimuli during encoding was associated with greater phase-amplitude coupling (PAC) between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. In Study 2, we next investigated cross-frequency PAC in the context of local effects of rhythm on memory encoding, when memory is superior for visual stimuli presented in-synchrony compared with out-of-synchrony with a background auditory beat [Hickey, P., Merseal, H., Patel, A. D., & Race, E. Memory in time: Neural tracking of low-frequency rhythm dynamically modulates memory formation. Neuroimage, 213, 116693, 2020]. We found that the mnemonic effect of rhythm in this context was again associated with increased cross-frequency PAC between entrained low-frequency (delta) oscillations and higher-frequency (gamma) oscillations. Furthermore, the magnitude of gamma power modulations positively scaled with the subsequent memory benefit for in- versus out-of-synchrony stimuli. Together, these results suggest that the influence of rhythm on memory encoding may reflect the temporal coordination of higher-frequency gamma activity by entrained low-frequency oscillations.

Goal-directed attention transforms both working and long-term memory representations in the human parietal cortex.

The abundance of distractors in the world poses a major challenge to our brain's limited processing capacity, but little is known about how selective attention modulates stimulus representations in the brain to reduce interference and support durable target memory. Here, we collected functional magnetic resonance imaging (fMRI) data in a selective attention task in which target and distractor pictures of different visual categories were simultaneously presented. Participants were asked to selectively process the target according to the effective cue, either before the encoding period (i.e., perceptual attention) or the maintenance period (i.e., reflective attention). On the next day, participants were asked to perform a memory recognition task in the scanner in which the targets, distractors, and novel items were presented in a pseudorandom order. Behavioral results showed that perceptual attention was better at enhancing target memory and reducing distractor memory than reflective attention, although the overall memory capacity (memory for both target and distractor) was comparable. Using multiple-voxel pattern analysis of the neural data, we found more robust target representation and weaker distractor representation in working memory for perceptual attention than for reflective attention. Interestingly, perceptual attention partially shifted the regions involved in maintaining the target representation from the visual cortex to the parietal cortex. Furthermore, the targets and distractors simultaneously presented in the perceptual attention condition showed reduced pattern similarity in the parietal cortex during retrieval compared to items not presented together. This neural pattern repulsion positively correlated with individuals' recognition of both targets and distractors. These results emphasize the critical role of selective attention in transforming memory representations to reduce interference and improve long-term memory performance.

The cortical amygdala consolidates a socially transmitted long-term memory.

Social communication guides decision-making, which is essential for survival. Social transmission of food preference (STFP) is an ecologically relevant memory paradigm in which an animal learns a desirable food odour from another animal in a social context, creating a long-term memory1,2. How food-preference memory is acquired, consolidated and stored is unclear. Here we show that the posteromedial nucleus of the cortical amygdala (COApm) serves as a computational centre in long-term STFP memory consolidation by integrating social and sensory olfactory inputs. Blocking synaptic signalling by the COApm-based circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage or recall. COApm-mediated STFP memory consolidation depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus. STFP memory consolidation requires protein synthesis, suggesting a gene-expression mechanism. Deep single-cell and spatially resolved transcriptomics revealed robust but distinct gene-expression signatures induced by STFP memory formation in the COApm that are consistent with synapse restructuring. Our data thus define a neural circuit for the consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein-synthesis-dependent memory consolidation from memory acquisition, storage or retrieval.

Network motifs exhibiting a differential response to spaced and massed inputs.

One characteristic of long-term memory is the existence of an inverted U-shaped response to increasing intervals between training sessions, and consequently, an optimal spacing that maximizes memory formation. Current models of this spacing effect focus on specific molecular components and their interactions. Here, we computationally study the underlying network architecture, in particular, the potential of motif dynamics in qualitatively capturing the spacing effect in a manner that is independent of the animal model, biomolecular components, and the timescales involved. We define a common training and test protocol, and computationally identify network topologies that can qualitatively replicate the experimentally observed characteristics of the spacing effect. For 41 motifs derived from fundamental network architectures such as autoregulation, feedback, and feedforward motifs, we tested their capacity to manifest the spacing effect in terms of an inverted U-shaped response curve, using different combinations of stimulation protocols, response metrics, and kinetic parameters. Our findings indicate that positive feedback motifs where the stimulus enhances conversion reaction in the loop replicate the spacing effect across all response metrics, while feedforward motifs exhibit a metric-specific spacing effect. For some parameter combinations, linear cascades of activation and conversion reactions were found sufficient to qualitatively exhibit spacing effect characteristics.

Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory.

Histone proteins affect gene expression through multiple mechanisms, including through exchange with histone variants. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. Most notably, widely expressed variants of H2B remain elusive. We applied recently developed antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters, and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Further, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a mechanism linking histone variants to chromatin accessibility, transcriptional regulation, neuronal function, and memory. This work further identifies a widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.

Seizure Detection of EEG Signals Based on Multi-Channel Long- and Short-Term Memory-Like Spiking Neural Model.

Seizure is a common neurological disorder that usually manifests itself in recurring seizure, and these seizures can have a serious impact on a person's life and health. Therefore, early detection and diagnosis of seizure is crucial. In order to improve the efficiency of early detection and diagnosis of seizure, this paper proposes a new seizure detection method, which is based on discrete wavelet transform (DWT) and multi-channel long- and short-term memory-like spiking neural P (LSTM-SNP) model. First, the signal is decomposed into 5 levels by using DWT transform to obtain the features of the components at different frequencies, and a series of time-frequency features in wavelet coefficients are extracted. Then, these different features are used to train a multi-channel LSTM-SNP model and perform seizure detection. The proposed method achieves a high seizure detection accuracy on the CHB-MIT dataset: 98.25% accuracy, 98.22% specificity and 97.59% sensitivity. This indicates that the proposed epilepsy detection method can show competitive detection performance.