Lasting Memory Research Articles

ISPNE Opening Plenary: Creating lasting memories – Involvement of stress hormones and amygdala activation: Time: Thursday, 06/Sep/2018: 3:30pm–4:15pm

The neuropeptide oxytocin (OXT) may facilitate attention to social stimuli by influencing early stage bottom-up processing although findings in relation to different emotional expressions are inconsistent and its influence on top-down cognitive processing mechanisms unclear. In the current double-blind placebo (PLC) controlled between-subject design study we therefore recruited 71 male subjects (OXT = 34, PLC = 37) to investigate the effects of intranasal OXT (24IU) on both bottom-up attention allocation and top-down attention inhibition using a prosaccade and antisaccade paradigm incorporating social (neutral, happy, fearful, sad, angry faces) and non-social (oval shape) visual stimuli with concurrent eye movement acquisition. Results revealed a marginal significant interaction effect between treatment, condition and task (p = 0.054), with Bonferroni-corrected post-hoc tests indicating that OXT specifically increased antisaccade errors for social stimuli (ps < 0.04, effect sizes 0.46-0.88), but not non-social stimuli. Antisaccades are under volitional control and therefore this may indicate that OXT treatment reduced top-down inhibition. However, the overall findings are consistent with OXT acting to reduce top-down control of attention as a result of increasing bottom-up early attentional processing of social, but not non-social, stimuli in situations where the two systems are in potential conflict. Marked deficits in bottom-up attention allocation to social stimuli have been reported in autism spectrum disorder, within this context OXT may have the potential to increase early attention allocation towards social cues.

Lucky Boy in the Lucky Country: The Autobiography of Max Corden, Economist, edited by Werner MaxCorden. Published by Palgrave Macmillan, 2017, 243 pages, ISBN: 978-331965165-1, AU$ 149.00

Lucky Boy in the Lucky Country: The Autobiography of Max Corden, Economist, edited by Werner MaxCorden. Published by Palgrave Macmillan, 2017, 243 pages, ISBN: 978-331965165-1, AU$ 149.00

Tailoring relaxation dynamics and mechanical memory of crumpled materials by friction and ductility.

Crumpled sheets show slow mechanical relaxation and long lasting memory of previous mechanical states. By using uniaxial compression tests, the role of friction and ductility on the stress relaxation dynamics of crumpled systems is investigated. We find a material dependent relaxation constant that can be tuned by changing ductility and adhesive properties of the sheet. After a two-step compression protocol, nonmonotonic aging is reported for polymeric, elastomeric and metal sheets, with relaxation dynamics that are dependent on the material's properties. These findings can contribute to tailoring and programming of crumpled materials to get desirable mechanical properties.

Kito-ryu jujutsu and the desolation of Kodokan judo’s Koshiki-no-kata -Remembering Inoue Shoji (1927-2018)

Inoue Shoji (1927-2018) was born in Tokushimaprefecture, Japan. As a youngster he took up judo. Later, he studied Kito-ryu jujutsu for some time with Odaka Shigeru. During his professional career as a prison guard he followed up on an offer to become a judo therapist. In a dojo in the Yamashina-ku ward in Kyoto he taught both judo and a limited catalogue of Kito-ryu that included exercises that were adopted into Kodokan judo under the name koshiki-no-kata [The Antique Forms]. With Kodokan judo continuing to deteriorate into an ordinary sport and losing its core values and purpose, Inoue increasingly appreciated the traditional martial arts values preserved in Kito-ryu jujutsu. His enthusiasm was reflected in beginning to give public demonstrations at various events in Japan and becoming a representative of Kito-ryu in the Nihon Kobudo Kyokai. Inoue’s supreme moment of glory likely was his public demonstration in 2013 at the occasion of the Fifth International Judo Federation (IJF) World Kata Judo Championships held in Kyoto. It was this performance that introduced him to the international judo community and brought him certain fame. For most foreign judoka this was their first contact with Kito-ryu. Irrespective of the quality of Inoue’s display, his approach offered a counterweight against the Kodokan’s historic reinvention and the IJF sports kata caricature. Several video clips publicly available on YouTube remain as a lasting memory of his art. Inoue Shoji held the rank of Kodokan 8th dan, and peacefully died in Kyoto on October 30th, 2018.

It's All in the Details: Relations Between Young Children's Developing Pattern Separation Abilities and Hippocampal Subfield Volumes.

The ability to keep similar experiences separate in memory is critical for forming unique and lasting memories, as many events share overlapping features (e.g., birthday parties, holidays). Research on memory in young children suggests their memories often lack high-resolution details, i.e., show impoverished pattern separation (PS). Recently developed assessments of PS suitable for children allow us to relate the formation of distinct, detailed memories for the development of the hippocampus, a neural structure critical for this ability in adults. The hippocampus displays a protracted developmental profile and underlies the ability to form detailed memories. This study examined age-related differences in hippocampal subfield volumes in 4- to 8-year-old children and relations with performance on a mnemonic similarity task (MST) designed to index memory specificity. Results revealed age-moderated associations between MST performance and cornu ammonis 2-4/dentate gyrus subfields. Specifically, age-related differences in the ability to form detailed memories tracked with normative patterns of volume increases followed by reductions over this age range. That is, greater volume correlated with better performance in younger children, whereas smaller volume correlated with better performance in older children. These findings support the hypothesis that developmental differences in hippocampal circuitry contribute to age-related improvements in detailed memory formation during this period.

Potential killers exposed: tracking endogenous influenza-specific CD8+ T cells.

Current influenza A virus (IAV) vaccines stimulate antibody responses that are directed against variable regions of the virus, and are therefore ineffective against divergent strains. As CD8+ T cells target the highly conserved, internal IAV proteins, they have the potential to increase heterosubtypic immunity. Early T‐cell priming events influence lasting memory, which is required for long‐term protection. However, the early responding, IAV‐specific cells are difficult to monitor because of their low frequencies. Here, we tracked the dissemination of endogenous IAV‐specific CD8+ T cells during the initial phases of the immune response following IAV infection. We exposed a significant population of recently activated, CD25+CD43+ IAV‐specific T cells that were not detected by tetramer staining. By tracking this population, we found that initial T‐cell priming occurred in the mediastinal lymph nodes, which gave rise to the most expansive IAV‐specific CD8+ T‐cell population. Subsequently, IAV‐specific CD8+ T cells dispersed to the bronchoalveolar lavage and blood, followed by spleen and liver, and finally to the lung. These data provide important insight into the priming and tissue dispersion of an endogenous CD8+ T‐cell response. Importantly, the CD25+CD43+ phenotype identifies an inclusive population of early responding CD8+ T cells, which may provide insight into TCR repertoire selection and expansion. A better understanding of this response is critical for designing improved vaccines that target CD8+ T cells.

Gp96-Ig/Costimulator Combination Platform Improves T Cell Priming, Enhances Immunity and Memory

Abstract The recent excitement in the field of immuno-oncology has been driven largely by the clinical success of checkpoint inhibitors. However, 60–90% of patients are still failing to respond to these therapies. It is widely believed that approaches targeting multiple facets of the immune system, including combinations with checkpoint inhibition and costimulator agonism, will be required to improve patient outcomes. Heat Biologics has developed a next generation T cell activating platform called ComPACT (COMbination Pan-Antigen Cytotoxic Therapy) that incorporates expression of a tumor antigen chaperone (gp96-Ig) and a T cell costimulator (OX40L-Ig) within a single vaccine cell line to effectively prime and boost antigen-specific CD4+ and CD8+ T cells. Furthermore, ComPACT stimulates activation of CD127+KLRG1- memory precursor cells, and lacks the toxic systemic inflammatory cytokine production and proliferation of non-specific CD4+ T cells and Tregs observed with systemic administration of OX40 agonist antibodies. ComPACT also led to high frequencies of IFNγ+, TNFα+, granzyme B+ and IL-2+ antigen-specific CD8+ T cells at both priming and boosting. Here, we have further assessed ImPACT and ComPACT-OX40L in combination with the anti-PD1 checkpoint inhibitor and with expression of an additional cell-secreted T cell costimulator, TL1A-Ig. We show that these treatments synergize effectively to amplify antigen-specific T cells and program a memory response. The combination of ComPACT-OX40L/TL1A with αPD1 or αPD-L1 may therefore translate into an efficacious approach generate long lasting memory in immuno-oncology settings.

Nutritional value and taste play different roles in learning and memory in the honey bee (Apis mellifera)

Honey bees will learn to respond to an odor when their antennae are stimulated with sucrose, even if they are not fed during the conditioning phase. However, if they are not fed, the memory of this association is significantly reduced 24 h after conditioning. These results suggest that stimulation of proboscis with sucrose and/or the nutritional quality of the reward plays an important role in establishing a long lasting memory. Three sugars, xylose, sorbitol and mannitol, are used to investigate the relationship among learning, sensory perception and nutritional value. The proboscis extension reflex is used to show that honey bees cannot taste these sugars, whereas mortality data suggest that bees can metabolize all three sugars. Feeding with sorbitol or xylose during olfactory associative conditioning restores robust 24 h memories. However, when given a free choice between consuming sucrose alone or sucrose supplemented with these nutritional sugars, bees did not show a preference for food containing the higher nutritional content. Furthermore, bees did not ingest solutions containing only the tasteless sugar even when it was the only food source. Together, these results suggest that nutritional content and not just sensory information is important for establishing long term memories, but that bees may not be able to assess nutritional content when it is disassociated from taste.

PhUn in the Snow: 3rd Graders Learn About Exercise Physiology

Physiology Understanding (PhUn) week is an ongoing effective outreach program of the American Physiological Society. This annual event for K‐12 students is held every November. During PhUn week, students get to meet a physiologist and perform science activities. This past year a small private parochial school contacted me and asked me to come into the third grade class in January. The event started with an introduction to the job of a physiologist and an explanation of heart function. The students created their hypothesis Exercise increases heart rate and planned their experiment. The correct way to measure heart rate via the carotid artery was demonstrated by the physiologist and students took their baseline heart rate. Then together with their partner the students went outside to perform their experiment. There was fresh snowfall on the playground yet the students were undaunted to perform the exercise portion of the activity. One member of the student pair ran for three minutes around the perimeter of the playground. Upon stopping they measured their heart rate. The second member of the pair repeated the exercise and took their post exercise heart rate. The whole class went back into the classroom to discuss their results. A discussion was held and students stated their data from before (baseline) and after exercise. The students agreed that their data supported their hypothesis. The physiologist explained why the heart rate needs to increase with exercise. It is always a thrill to be able to work with young students and be the first scientist they have ever met. This PhUn week event is certain to create a lasting memory for both physiologist and students alike.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

2nd Grade Students Have PhUn Learning About Thermoregulation

Physiology Understanding (PhUn) week is a yearly event sponsored by the American Physiological Society (APS). As part of this annual event, physiologists visit K‐12 classrooms and teach students about physiology. While the event is usually held in November it can be held at different times of the year to accommodate students' and teachers' schedules. The different methods in which animals stay warm in the winter was the perfect topic to bring into the second grade classroom during the winter. Students learned the role of a physiologist and the definition of thermoregulation. The class was very interactive when describing the differences in how animals stay warm in the winter: hibernation, fur, huddling together, and warm winter jackets. The physiologist then focused the discussion on three animals: polar bear, human and bird. The degree to which the polar bear fur, human skin and bird's feathers provide insulation from the cold was discussed. To reinforce the knowledge learned, the students performed the Insulation Bag “hands‐in” activity. Three sets of hand mitts made from zipper lock bags were immersed into a bucket of ice water. One empty set of mitts mimicked human skin, a second set with bubble wrap in the mitts was used to mimic feathers and a third set had a layer of vegetable shortening to mimic the insulation of a polar bear. The students tested each type of bag and then determined in which mitt their hands were the warmest. They then met Phreezy bear (APS stuffed animal) and completing the activities in the APS Fun with Physiology activity book for grades 2–4. Each classroom was given an APS How do I Stay Warm poster to remember the lesson. This PhUn week event is sure to create a lasting memory for both students and physiologist alike.Support or Funding InformationAmerican Physiological SocietyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

(171) - Alterations in memories for fearful experiences among youth with chronic pain

Interpretation of survival salient stimuli, such as the detection of threat, constitutes a fundamental protective mechanism in an organism. In chronic pain, this response mechanism becomes faulty, contributing to a distorted perception of threat. Stimuli that are improperly perceived as threatening can leave lasting memory traces that interfere with the recollection of actual pain experiences. In this study, we examined how adolescents with chronic pain encoded and retrieved memories of emotionally salient stimuli from a differential fear conditioning paradigm. Patients ages 10–24 (n = 33) and cohort matched healthy peers (HC, n = 14) participated in the “Screaming Lady” fear conditioning paradigm to examine contingency learning. Patients completed the Fear of Pain Questionnaire (FOPQ) and were examined across high (HF, n = 12), moderate (MF, n = 7), and low fear (LF, n = 12) levels, in comparison to the healthy counterparts. All participants were asked a series of questions pertaining to feelings of anxiety or unpleasantness regarding the conditioned stimulus (CS+) and neutral stimulus (CS-) on the day of the experiment and one month post-experiment via a telephone memory interview. High fear participants reported increased feelings of anxiety towards the CS- at the one-month follow up mark (P < .05), and reported marginally significant (P = .08) increased feelings of unpleasantness towards the CS-. An analysis of the reported unconditioned stimulus (UCS, unpleasant scream) frequency revealed that pain groups tended to report higher frequencies for the CS + than the control group. We also examined memory interviews qualitatively with NVivo software for memory accuracy, content, and affect. These initial findings suggest a distortion in memory of threat among pediatric chronic pain patients compared to healthy peers. In future work, we will investigate additional covariates such as state and trait anxiety to identify additional factors involved in the distortion of fear memories.

In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo.

Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.

Creating lasting memories in end of life care

Lead nurse Candice St John has a unique way of helping bereaved families remember their children

The mysteries of remote memory.

Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process—the standard theory of memory consolidation—would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might already ab ovo be encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges.This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.

Flexible electronics: Lasting memories are in sight

Flexible electronics: Lasting memories are in sight

ПРОФЕСОР ВОЛОДИМИР ПАВЛОВИЧ ЧОРНІЙ: ЖИТТЯ І ТВОРЧА ДІЯЛЬНІСТЬ

Abstract Background: Volodymyr Pavlovych Chorniy – a famous Ukrainian Slavicist, the Professor of the Department of History of Central and Eastern Europe, the Director of the Institute of Slavic Studies of Ivan Franko National University of Lviv, the perennial editor-in-chief of the scientific journal “Problems of Slavic Studies”, the founder and chairman of the Organizing Committee of International Slavist Colloquium – passed away on February 3, 2018. During the life of the scientist many publications have appeared concerning his biography and scientific achievements, but as a rule, they are of a very general, outline nature and concern only specific areas or just results of his activity. Taking into consideration the fact that a lot of what have been done by Volodymyr Pavlovych has long been recognized by the general scientific community, the figure of the Professor undoubtedly deserves a more thorough and comprehensive study. Purpose : The article offered to readers has several main goals. Above all, it is to honor the memory of the scientist, as well as to highlight the major stages of his life and creative activity designed to initiate their further, more in-depth scientific research. Results : The life and work of Volodymyr Pavlovych based on a wide range of sources (autobiographical notes, family archive, oral evidence of relatives and colleagues as well as other materials) have been characterized in detail for the first time. The attempt is to analyze comprehensively the scientific heritage of the scientist and its role in the development of Ukrainian Slavic science has also been made. The special attention has been paid to different areas of the professor's scientific-organizational and teaching work, as well as the peculiarities of his outlook and talent. Everybody, who knew Volodymyr Pavlovych, has a lasting memory of a good, decent, sensitive and loving Man, a talented Scientist, a wise Teacher and Mentor who has been engaged in his favorite work with admirable honesty and perseverance for more than half a century; his versatile creative activity has become the part of the history of Franko University and marked an entire era in Ukrainian Slavic science contributing to the preservation and multiplication of its best achievements and traditions. Key words : Volodymyr Pavlovych Chorniy, biography, creative activity, scientific heritage, history, Bulgarian studies, Slavistics.

Disruption of Perceptual Learning by a Brief Practice Break

Some forms of associative learning require only a single experience to create a lasting memory [1, 2]. In contrast, perceptual learning often requires extensive practice within a day for performance to improve across days [3, 4]. This suggests that the requisite practice for durable perceptual learning is integrated throughout each day. If the total amount of daily practice is the only important variable, then a practice break within a day should not disrupt across-day improvement. To test this idea, we trained human listeners on an auditory frequency-discrimination task over multiple days and compared the performance of those who engaged in a single continuous practice session each day [4] with those who were given a 30-min break halfway through each practice session. Continuous practice yielded significant perceptual learning [4]. In contrast, practice with a rest break led to no improvement, indicating that the integration process had decayed within 30min. In a separate experiment, a 30-min practice break also disrupted durable learning on a non-native phonetic classification task. These results suggest that practice trials are integrated up to a learning threshold within a transient memory store before they are sent en masse into a memory that lasts across days. Thus, the oft cited benefits of distributed over massed training [5, 6] may arise from different mechanisms depending on whether the breaks occur before or after a learning threshold has been reached. Trial integration could serve as an early gatekeeper to plasticity, helping to ensure that longer-lasting changes are only made when deemed worthwhile.

Intermittent Ethanol during Adolescence Leads to Lasting Behavioral Changes in Adulthood and Alters Gene Expression and Histone Methylation in the PFC.

Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC) transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task. As adults, mice were tested for cognitive changes using the novel object recognition task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge ethanol altered ethanol sensitivity in young mice and led to lasting memory deficits in the object recognition test and greater ethanol sensitivity in adulthood. Using genomic profiling of transcripts in the PFC, we found that binge ethanol reduced myelin-related gene expression and altered chromatin modifying genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that ethanol’s actions on histone methylation may be a switch for future transcriptional changes that underlie the behavioral changes lasting into adulthood.

Relevance of Spatial Heterogeneity of Immune Infiltration for Predicting Risk of Recurrence After Endocrine Therapy of ER+ Breast Cancer.

Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole. The prognostic significance of immune scores was compared with Oncotype DX 21-gene recurrence score (RS), PAM50 risk of recurrence (ROR) score, IHC4, and clinical treatment score, available for 963 patients. Statistical tests were two-sided. Scores of immune cell abundance were not associated with recurrence-free survival. In contrast, high immune spatial scores indicating increased cell spatial clustering were associated with poor 10-year, early (0-5 years), and late (5-10 years) recurrence-free survival (Immune Hotspot: LR-χ2 = 14.06, P < .001, for 0-10 years; LR-χ2 = 6.24, P = .01, for 0-5 years; LR-χ2 = 7.89, P = .005, for 5-10 years). The prognostic value of spatial scores for late recurrence was similar to that of IHC4 and RS in both populations, but was not as strong as other tests in comparison for recurrence across 10 years. These results provide a missing link between tumor immunity and disease outcome in ER+ disease by examining tumor spatial architecture. The association between spatial scores and late recurrence suggests a lasting memory of protumor immunity that may impact disease progression and evolution of endocrine treatment resistance, which may be exploited for therapeutic advances.

Oquendo Recounts Past Year’s Victories, Coming Year’s Challenges

Oquendo Recounts Past Year’s Victories, Coming Year’s Challenges