Contextual Memory Research Articles

Misinformation in social interaction: examining the role of discussion

ABSTRACT Memory is a reconstructive process that is prone to intrusions and distortions. These processes can be amplified by the emergence and propagation of false information in the social environment. While the acceptance of misinformation is well documented in individual memory tasks, the production of false memories in social interaction contexts presents mixed findings. One factor that may contribute to these inconsistencies is the collaboration method used, which may vary in the opportunities they offer for more (free-for-all) or less (turn-taking) discussion. The current study contrasts these two collaboration methods in misinformation acceptance. Participants watched a video, followed by an individual recall task. Then, they completed a questionnaire containing true and misinformation about the video, individually or in pairs (using free-for-all or turn-taking methods). Finally, participants were given a new individual recall task. Results revealed that participants responding to the questionnaire using the free-for-all method were more accurate and accepted less misinformation (vs. turn-taking and individual conditions). Critically, in the second individual recall, these participants also recalled less misinformation from the questionnaire than those in the turn-taking condition. These results suggest that discussion opportunities during social interaction enhance correction and error-pruning and reduce misinformation acceptance.

Requisite role of dorsal raphé in contextual cocaine-memory reconsolidation

Memory reconsolidation is a process by which labile drug memories are restabilized in long-term memory stores, permitting their enduring control over drug-seeking behaviors. In the present study, we investigated the involvement of the dorsal raphé nuclei (DRN) in cocaine-memory reconsolidation. Sprague-Dawley rats (male, female) were trained to self-administer cocaine in a distinct environmental context to establish contextual drug memories. They then received extinction training in a different context. Next, the rats were re-exposed to the cocaine-predictive context for 15 min to reactivate their cocaine memories or remained in their home cages (no-reactivation control). Memory reactivation was sufficient to increase c-Fos expression, an index of neuronal activation, in the DRN, but not in the median raphé nuclei, during reconsolidation, compared to no reactivation. To determine whether DRN neuronal activity was necessary for cocaine-memory reconsolidation, rats received intra-DRN baclofen plus muscimol (BM; GABAB/A agonists) or vehicle microinfusions immediately after or 6 h after a memory reactivation session conducted with or without lever access. The effects of DRN functional inactivation on long-term memory strength, as indicated by the magnitude of context-induced cocaine seeking, were assessed 72 h later. Intra-DRN BM treatment immediately after memory reactivation with or without lever access attenuated subsequent context-induced cocaine-seeking behavior, independent of sex. Conversely, BM treatment in the adjacent periaqueductal gray (PAG) immediately after memory reactivation, or BM treatment in the DRN 6 h after memory reactivation, did not alter responding. Together, these findings indicate that the DRN plays a requisite role in maintaining cocaine-memory strength during reconsolidation.

Hippocampal Engrams and Contextual Memory.

Memories are not formed in a vacuum and often include rich details about the time and place in which events occur. Contextual stimuli promote the retrieval of events that have previously occurred in the encoding context and limit the retrieval of context-inappropriate information. Contexts that are associated with traumatic or harmful events both directly elicit fear and serve as reminders of aversive events associated with trauma. It has long been appreciated that the hippocampus is involved in contextual learning and memory and is central to contextual fear conditioning. However, little is known about the underlying neuronal mechanisms underlying the encoding and retrieval of contextual fear memories. Recent advancements in neuronal labeling methods, including activity-dependent tagging of cellular ensembles encoding memory ("engrams"), provide unique insight into the neural substrates of memory in the hippocampus. Moreover, these methods allow for the selective manipulation of memory ensembles. Attenuating or erasing fear memories may have considerable therapeutic value for patients with post-traumatic stress disorder or other trauma- or stressor-related conditions. In this chapter, we review the role of the hippocampus in contextual fear conditioning in rodents and explore recent work implicating hippocampal ensembles in the encoding and retrieval of aversive memories.

The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

Lower constraint testing enhances the testing effect for some contextual details but not others.

Retrieval practice has been shown to be an effective means of learning new information, a memory phenomenon known as the testing effect or the retrieval practice effect. Some work suggests that the magnitude of the testing effect can be enhanced when the test used for retrieval practice uses fewer cues to retrieve previously studied information. It is unclear, however, whether such testing benefits extend to peripheral contextual details associated with studied materials (e.g., location where stimuli appear, font color in which items are presented, etc.). In this experiment, we examine both item memory (i.e., memory for the studied items) and context memory under conditions where the intervening test offers fewer cues (i.e., lower constraint) compared to more cues (higher constraint) to better understand item and context memory testing effects. Participants first studied word pairs presented in one of eight locations as well as in either red or green font color. Then, in the re-exposure phase, participants processed materials in two types of intervening tests (lower constraint and a higher constraint test) as well as in a restudy condition, before a final memory test. For item memory, results showed that memory was better in the lower constraint testing condition compared to both the higher constraint testing condition as well as the restudy (control) condition. For context memory, results indicated improved memory for location context under lower constraint testing compared to both higher constraint testing and restudy conditions. There was no difference in memory, however, for color context across all conditions. Overall, these findings suggest that providing fewer cues to aid retrieval in the intervening test can induce better memory for both items as well as some contextual details.

Exploring protocol development: Implementing systematic contextual memory to enhance real-time fMRI neurofeedback.

The goal of this study was to explore the development and implementation of a protocol for real-time fMRI neurofeedback (rtfMRI-nf) and to assess the potential for enhancing the selective brain activation using stimuli from Virtual Reality (VR). In this study we focused on two specific brain regions, supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). Publications by other study groups have suggested impaired function in these specific brain regions in patients with the diagnoses Attention Deficit Hyperactivity Disorder (ADHD) and Tourette's Syndrome (TS). This study explored the development of a protocol to investigate if attention and contextual memory may be used to systematically strengthen the procedure of rtfMRI-nf. We used open-science software and platforms for rtfMRI-nf and for developing a simulated repetition of the rtfMRI-nf brain training in VR. We conducted seven exploratory tests in which we updated the protocol at each step. During rtfMRI-nf, MRI images are analyzed live while a person is undergoing an MRI scan, and the results are simultaneously shown to the person in the MRI-scanner. By focusing the analysis on specific regions of the brain, this procedure can be used to help the person strengthen conscious control of these regions. The VR simulation of the same experience involved a walk through the hospital toward the MRI scanner where the training sessions were conducted, as well as a subsequent simulated repetition of the MRI training. The VR simulation was a 2D projection of the experience.The seven exploratory tests involved 19 volunteers. Through this exploration, methods for aiming within the brain (e.g. masks/algorithms for coordinate-system control) and calculations for the analyses (e.g. calculations based on connectivity versus activity) were updated by the project team throughout the project. The final procedure involved three initial rounds of rtfMRI-nf for learning brain strategies. Then, the volunteers were provided with VR headsets and given instructions for one week of use. Afterward, a new session with three rounds of rtfMRI-nf was conducted. Through our exploration of the indirect effect parameters - brain region activity (directed oxygenated blood flow), connectivity (degree of correlated activity in different regions), and neurofeedback score - the volunteers tended to increase activity in the reinforced brain regions through our seven tests. Updates of procedures and analyses were always conducted between pilots, and never within. The VR simulated repetition was tested in pilot 7, but the role of the VR contribution in this setting is unclear due to underpowered testing. This proof-of-concept protocol implies how rtfMRI-nf may be used to selectively train two brain regions (SMA and rIFG). The method may likely be adapted to train any given region in the brain, but readers are advised to update and adapt the procedure to experimental needs.

Memory wars: A solution to the conflict

The validity of dissociative memory in forensic contexts and the causes of the so-called "memory wars" are discussed. Misconceptions between clinical and forensic psychology, a deficient definition of amnesia, and the difficulties inherent in studying traumatic memories contribute to the persistence of this controversy. Particularly in the field of forensic psychology, the debate could be attributed to the lack of consensus on scientific evidence. Psychologists need to establish an empirical foundation to understand better the mechanisms of memory involved in remembering and forgetting traumatic memories. The Continuous Accessibility Model of Memory is outlined to explain the retrieval of the different degrees of accessibility to autobiographical memories based on different factors.

Effectiveness of an Occupational Therapy Memory Strategy Education Group Intervention on Memory Difficulties and Activities of Daily Living Performance among the Geriatric Population: A Quasi-experimental Study

Introduction: Memory deficits are one of the common indications of cognitive aging, and they are an essential component for completing day-to-day activities in an effective, timely, and safe manner. Disturbances in memory can have a major impact on an individual’s performance in all areas of occupation. Memory alterations have a substantial influence on numerous elements of everyday living, including sentiments and conceptions of self, connections with others, participation in Activities of Daily Living (ADL), and engagement in leisure activities. Aim: To determine the effectiveness of an occupational therapy Memory Strategy Education Group (MSEG) intervention on memory difficulties and its impact on ADL performance among the geriatric population. Materials and Methods: The present quasi-experimental pre-post-test pilot study was conducted at Department of Occupational Therapy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India. A total of 10 participants aged 60 years and above were recruited from a community setting through convenience sampling and were divided into an experimental group (n=5) and a control group (n=5). The experimental group participants received MSEG intervention, while the control group participants received conventional occupational therapy memory intervention for three weeks. The Canadian Occupational Performance Measure (COPM), Contextual Memory Test (CMT), and Functional Independence Measure (FIM) were used to measure occupational performance, memory, and ADL. The outcome measure scores within groups were analysed using the Wilcoxon signed-rank test, and the comparison of outcome measures between the groups was analysed using the MannWhitney U test. An alpha level of p=0.05 was considered to be statistically significant. Statistical Package for Social Sciences (SPSS) 24.0 version was used to analyse the data. Results: In the present study, a total of 10 participants from the age group of 60-75 years (mean age=67.4 years) were included, and each group (control and experimental) consisted of five participants (3 males and 2 females). The results showed that there was a significant difference (p<0.05) between the post-test scores of the experimental and control groups in COPM-Performance and CMT (p=0.032; p=0.018, respectively). However, there was no statistically significant difference (p>0.05) in the post-test scores of the experimental and control groups in FIM (p=0.347). Further analysis revealed a clinically significant difference between the control and experimental groups in post-test scores. Conclusion: The results of the study concluded that the MSEG intervention is effective in improving memory difficulties in the geriatric population but had a lesser effect on improving ADL performance.

Музей-усадьба в русской литературе: нарратологический аспект

In the 20th century, the estate became a phenomenon of the historical past. This process began at the turn of the 19th and 20th century: the ghostliness of the estate culture and its archaic character are commonplace in literature of that time (A.P. Chekhov’s “The Cherry Orchard,” G.I. Chulkov’s “The Sister,” S.M. Gorodetsky’s “Sutulov’s Nest,” A.M. Kuzmin’s “The Deceased in the House”). At the same time, the problem of narrative ordering of numerous events and persons connected with the estate heritage comes to the fore. In the works of the first half of the 20th century, it appears as the aspect of comprehension of the pre-revolutionary epoch (N. Ognev’s “Kostya Ryabtsev’s Diary,” M.M. Prishvin’s “The Worldly Cup,” I.A. Bunin’s “The Imminent Spring”). But the wider the museification of the estate spreads, the more urgent becomes the question of memory narratives as a specific mechanism of cultural self-consciousness. The article analyzes S.D. Dovlatov’s story “Reserve” through the terminology paradigm of contemporary narrative theory. The writer shows how to acquire a frankly artificial (simulative) character in the estate museum context memory narratives, the “alien” estate past never becomes “his”/“her own” present of the narrator (guide) and his addressee (tourist).

Beyond Appearance: Multi-Frame Spatio-Temporal Context Memory Networks for Efficient and Robust Video Object Segmentation.

Current video object segmentation approaches primarily rely on frame-wise appearance information to perform matching. Despite significant progress, reliable matching becomes challenging due to rapid changes of the object's appearance over time. Moreover, previous matching mechanisms suffer from redundant computation and noise interference as the number of accumulated frames increases. In this paper, we introduce a multi-frame spatio-temporal context memory (STCM) network to exploit discriminative spatio-temporal cues in multiple adjacent frames by utilizing a multi-frame context interaction module (MCI) for memory construction. Based on the proposed MCI module, a sparse group memory reader is developed to enable efficient sparse matching during memory reading. Our proposed method is generic and achieves state-of-the-art performance with real-time speed on benchmark datasets such as DAVIS and YouTube-VOS. In addition, our model exhibits robustness to sparse videos with low frame rates.

СОХРАНЕНИЕ ИСТОРИЧЕСКОЙ ПАМЯТИ В ТОПОНИМИЧЕСКОМ ПРОСТРАНСТВЕ РОСТОВА-НА-ДОНУ: НА ПРИМЕРЕ ПРИСВОЕНИЯ ПОЧЕТНЫХ НАИМЕНОВАНИЙ ШКОЛАМ

Researchers consider issues related to the study of historical memory in a broad context, because the perception and display of its individual plots can be studied from various angles, both material in the form of, for example, a memorial space, and public and state practices, such as holding fes-tive events. Research into toponymic space entails direct touch with the sphere of historical memory. With this phrasing of the topic, the toponymy of Rostov-on-Don appears to be a very in-teresting route for thinking about specific practices of conserving historical memory, such as naming schools after historical figures. Being a part of the general toponymic space of the city, they are a vivid marker of how the practices of implementing toponymic policy and preserving historical memory interact at the present stage. The authors of this article believe that studying toponymic space entails direct work on the study of the key subjects of historical memory, which are fixed in public space, by designating not just streets or squares, but also individual institu-tions. Based on the analysis of the complex of honorary names of Rostov-on-Don schools, the time of their appearance, as well as the semantic load, it seems natural to draw conclusions about the most significant and relevant subjects of historical memory preserved in the 1990s-2020s on the map of the capital of the South and the gates of the North Caucasus.

Binge ethanol exposure in advanced age elevates neuroinflammation and early indicators of neurodegeneration and cognitive impairment in female mice

Binge drinking is rising among aged adults (>65 years of age), however the contribution of alcohol misuse to neurodegenerative disease development is not well understood. Both advanced age and repeated binge ethanol exposure increase neuroinflammation, which is an important component of neurodegeneration and cognitive dysfunction. Surprisingly, the distinct effects of binge ethanol exposure on neuroinflammation and associated degeneration in the aged brain have not been well characterized. Here, we establish a model of intermittent binge ethanol exposure in young and aged female mice to investigate the effects of advanced age and binge ethanol on these outcomes. Following intermittent binge ethanol exposure, expression of pro-inflammatory mediators (tnf-α, il-1β, ccl2) was distinctly increased in isolated hippocampal tissue by the combination of advanced age and ethanol. Binge ethanol exposure also increased measures of senescence, the nod like receptor pyrin domain containing 3 (NLRP3) inflammasome, and microglia reactivity in the brains of aged mice compared to young. Binge ethanol exposure also promoted neuropathology in the hippocampus of aged mice, including tau hyperphosphorylation and neuronal death. We further identified advanced age-related deficits in contextual memory that were further negatively impacted by ethanol exposure. These data suggest binge drinking superimposed with advanced age promotes early markers of neurodegenerative disease development and cognitive decline, which may be driven by heightened neuroinflammatory responses to ethanol. Taken together, we propose this novel exposure model of intermittent binge ethanol can be used to identify therapeutic targets to prevent advanced age- and ethanol-related neurodegeneration.

Historiography and Collective Memory

Zakhor is the commandment of remembrance often repeated in the Torah. It is also the title of an indispensable book for reflection on Jewish identity in relation to historiography. In this article, I will start with the thesis of the Jewish historian Yerushalmi to discuss the relationship between memory and historiography in the Jewish context and beyond. Yerushalmi pointed out a distance between collective memory and historiography that is an interesting starting point for reflection on the possibilities of a non-westernized historiography. The text is divided into an introduction, three topics that aim: to present Yerushalmi’s book; to present the main comments to the book; to reflect on the place or non-place of the national element in a Jewish history; and a conclusion. Thus, I will question the tension between memory and history and a possible approximation that goes beyond the modern notion of historiography. Thus, reading Yerushalmi’s thesis as a possibility of rethinking the instruments of historiography.

Post-operative cognitive dysfunction is exacerbated by high-fat diet via TLR4 and prevented by dietary DHA supplementation

Post-operative cognitive dysfunction (POCD) is an abrupt decline in neurocognitive function arising shortly after surgery and persisting for weeks to months, increasing the risk of dementia diagnosis. Advanced age, obesity, and comorbidities linked to high-fat diet (HFD) consumption such as diabetes and hypertension have been identified as risk factors for POCD, although underlying mechanisms remain unclear. We have previously shown that surgery alone, or 3-days of HFD can each evoke sufficient neuroinflammation to cause memory deficits in aged, but not young rats. The aim of the present study was to determine if HFD consumption before surgery would potentiate and prolong the subsequent neuroinflammatory response and memory deficits, and if so, to determine the extent to which these effects depend on activation of the innate immune receptor TLR4, which both insults are known to stimulate. Young-adult (3mo) & aged (24mo) male F344xBN F1 rats were fed standard chow or HFD for 3-days immediately before sham surgery or laparotomy. In aged rats, the combination of HFD and surgery caused persistent deficits in contextual memory and cued-fear memory, though it was determined that HFD alone was sufficient to cause the long-lasting cued-fear memory deficits. In young adult rats, HFD + surgery caused only cued-fear memory deficits. Elevated proinflammatory gene expression in the hippocampus of both young and aged rats that received HFD + surgery persisted for at least 3-weeks after surgery. In a separate experiment, rats were administered the TLR4-specific antagonist, LPS-RS, immediately before HFD onset, which ameliorated the HFD + surgery-associated neuroinflammation and memory deficits. Similarly, dietary DHA supplementation for 4 weeks prior to HFD onset blunted the neuroinflammatory response to surgery and prevented development of persistent memory deficits. These results suggest that HFD 1) increases risk of persistent POCD-associated memory impairments following surgery in male rats in 2) a TLR4-dependent manner, which 3) can be targeted by DHA supplementation to mitigate development of persistent POCD.

Hypothalamic CRH neurons represent physiological memory of positive and negative experience

Recalling a salient experience provokes specific behaviors and changes in the physiology or internal state. Relatively little is known about how physiological memories are encoded. We examined the neural substrates of physiological memory by probing CRHPVN neurons of mice, which control the endocrine response to stress. Here we show these cells exhibit contextual memory following exposure to a stimulus with negative or positive valence. Specifically, a negative stimulus invokes a two-factor learning rule that favors an increase in the activity of weak cells during recall. In contrast, the contextual memory of positive valence relies on a one-factor rule to decrease activity of CRHPVN neurons. Finally, the aversive memory in CRHPVN neurons outlasts the behavioral response. These observations provide information about how specific physiological memories of aversive and appetitive experience are represented and demonstrate that behavioral readouts may not accurately reflect physiological changes invoked by the memory of salient experiences.

‘Pou maumahara’, ‘the memory place’: Remembrance and material cultures of colonial conflict at the Auckland War Memorial Museum Tāmaki Paenga Hira

This article explores how material objects reveal patterns of remembrance in the public histories of the nineteenth-century New Zealand Wars fought between British regiments and colonial forces and Māori hapū and iwi (tribal groups). It is based on collections research conducted at the Auckland War Memorial Museum which conceptualises a new gallery displaying stories and objects relating to the wars. Bringing together museology and historiography, the article argues that an engagement with the material culture of the New Zealand Wars and public lexicons of memory in a museum context offer opportunities to move beyond national narratives. Just as these colonial conflicts reconfigured the materiality of violence and collective belonging, so too do museum-based objects activate the presentation of these histories in light of new public needs since 2017.

Integrative Analysis of Morphine-Induced Differential Circular RNAs and ceRNA Networks in the Medial Prefrontal Cortex.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs. Despite the fact that the functional mechanisms of most circRNAs remain unknown, emerging evidence indicates that circRNAs could sponge microRNAs (miRNAs), bind to RNA binding proteins (RBP), and even be translated into protein. Recent research has demonstrated the crucial roles played by circRNAs in neuropsychiatric disorders. The medial prefrontal cortex (mPFC) is a crucial component of drug reward circuitry and exerts top-down control over cognitive functions. However, there is currently limited knowledge about the correlation between circRNAs and morphine-associated contextual memory in the mPFC. Here, we performed morphine-induced conditioned place preference (CPP) in mice and extracted mPFC tissue for RNA-sequencing. Our study represented the first attempt to identify differentially expressed circRNAs (DEcircRNAs) and mRNAs (DEmRNAs) in the mPFC after morphine-induced CPP. We identified 47 significantly up-regulated DEcircRNAs and 429 significantly up-regulated DEmRNAs, along with 74 significantly down-regulated DEcircRNAs and 391 significantly down-regulated DEmRNAs. Functional analysis revealed that both DEcircRNAs and DEmRNAs were closely associated with neuroplasticity. To further validate the DEcircRNAs, we conducted qRT-PCR, Sanger sequencing, and RNase R digestion assays. Additionally, using an integrated bioinformatics approach, we constructed ceRNA networks and identified critical circRNA/miRNA/mRNA axes that contributed to the development of morphine-associated contextual memory. In summary, our study provided novel insights into the role of circRNAs in drug-related memory, specifically from the perspective of ceRNAs.

Cognitive decline and affective alterations in SCA2-58Q mice

The cerebellum is traditionally recognized as a brain region dedicated to motor control and movement coordination. Yet, the growing body of research has recently highlighted the cerebellar role in cognitive processes, learning, and emotional states. Patients with damage to this particular region of the brain exhibit deficiencies in verbal communication, impaired speech, executive functions, and memory, along with various affective disorders [1]. In the field of neurodegeneration research, the cerebellum is primarily recognized for its role in the onset of spinocerebellar ataxias (SCAs). SCA2 is an autosomal dominant polyglutamine-related neurological disorder resulting from a notable escalation in the number of CAG triplet repeats that encode the amino acid glutamine in the ATXN2 gene. The mutated protein ataxin-2 fails to perform its molecular functions, disrupting calcium homeostasis and cellular activity, ultimately resulting in widespread Purkinje neuron death in the cerebellar cortex [2]. In our research, we used SCA2-58Q transgenic mice that express the mutant human ataxin-2 gene under the action of the Purkinje-specific promoter (PCP2/L7). Each of these tests were aimed at evaluating specific aspects of the mice’s behavior. This model enabled to investigate the direct involvement of Purkinje cells in the cognitive and affective symptoms associated with SCA2. Our team conducted three behavioral tests to determine the anxiolytic behavior: the open field test, the novelty suppressed feeding test, and the light-dark place preference test. The novel object recognition and fear conditioning tests were used to assess recognition and contextual memory, respectively. The Morris water maze test was conducted to evaluate spatial learning and memory. The researchers assessed depression and anhedonia levels using the forced swimming, tail suspension, and sucrose preference tests. The study revealed anxiety, spatial memory impairment, and affective decline in 7–8-month-old SCA2 mice. Previous results of the beam walk test [3, 4] indicated a delay in motor skill development in SCA2-58Q mice, which began at 8–10 months of age. This indicates that cognitive decline and affective changes occur before the primary motor impairment in spinocerebellar ataxia type 2. Currently, there is no disease-modifying treatment for SCA2, and patients are typically given supportive therapy and treatment for individual symptoms. In conclusion, our research provides a more comprehensive clinical picture and takes a step towards optimizing the diagnosis and selecting more effective therapy options for SCA2.

Exosomes from WT Mice Enhances Memory Recall-induced IEG Expression and Rescue Dendritic Spines Deficit in Angelman Syndrome Mice

Angelman syndrome (AS) is a rare neurogenetic disorder caused by deletion or mutations in the UBE3A gene, which lead to the deficiency of the UBE3A protein in neurons. UBE3A is crucial for normal neuronal communication, as it regulates the turnover of synaptic proteins and synaptic plasticity. Exosomes, small extracellular vesicles released by various cells, including neurons, play important roles in intercellular communication. Exosomes contain a variety of molecules, including proteins and nucleic acids, and can transfer these components between cells. Emerging evidence indicates that exosomes are critical for normal brain functions, and in recent years many studies have investigated the therapeutic potential of exosomes as vehicles for delivering therapeutic cargoes in various neurological disorders. In this study, we investigated the potential role of exosomes in regulating spine morphology in AS mice. Our results showed that activation of the lysosomal calcium channel TRPML1 stimulated exosome release from synaptosomes prepared from adult WT mice, but not from synaptosomes prepared from adult AS mice. Intriguingly, UBE3A was present in exosomes secreted from WT mice. It has been previously shown that hippocampal neurons of AS mice exhibit fewer dendritic spines, as compared to those from WT mice. Incubation of cultured hippocampal neurons from AS mice with conditioned medium from cultured hippocampal neurons from WT mice rescued the number of dendritic spines. Our data suggest that this effect is most likely due to exosomes in the medium, since purified exosomes from conditioned medium of WT neurons produced a similar rescue effect in cultured neurons from AS mice. Moreover, intravenous injection of exosomes prepared from synaptosomes of adult WT mice seemed to enhance contextual memory recall and associated immediate early gene (IEG) expression, and te number of dendritic spines in CA1 pyramidal neurons in adult AS mice. Whether and to what degree UBE3A present in WT exosomes participates in the rescue of AS neuronal morphology remains to be determined. Together, these results reveal both altered exosomal secretion and composition in AS mice. Treatment of AS neurons or adult AS mice with exosomes rescued dendritic spine deficits in vitro and in vivo. These results open new therapeutical approaches for using exosomes as a potential treatment for this disease.

BENDI: Improving Cognitive Assessments in Toddlers and Children with Down Syndrome Using Stealth Assessment.

Cognitive assessment is a fundamental step in diagnosing intellectual and developmental disabilities, designing interventions, and evaluating their impact. However, developed and developing countries have different access to tools designed for these purposes. Our goal was to develop a battery for cognitive assessment mediated by digital technology that allows the exploration of cognitive domains (inhibitory control, attention, motor ability, and context memory) in children with Down Syndrome (DS) in Chile. Four tasks, based on established experimental paradigms modified to provide a game-like experience, were tested in 68 children with DS from 20 months to 12 years of age. We present evidence of reliability based on internal consistency and split-half analyses, with results ranging from adequate to excellent. Regarding validity, factorial and correlational analyses show evidence consistent with what was theoretically expected of internal structure, convergence, and divergence with other measures. Expected age trajectories were observed as well. Our data offer evidence that supports the use of tasks based on touch-screen devices for cognitive assessment in the population with DS. The tasks also have a low cultural load, so they could be validated and used in other contexts without the need for an adaptation process.