A retrieval-specific mechanism of adaptive forgetting in the mammalian brain

Forgetting is a ubiquitous phenomenon that is actively promoted in many species. How and whether organisms’ behavioral goals drive which memories are actively forgotten is unknown. Here we show that processes essential to controlling goal-directed behavior trigger active forgetting of distracting memories that interfere with behavioral goals. When rats need to retrieve particular memories to guide exploration, it reduces later retention of other memories encoded in that environment. As with humans, this retrieval-induced forgetting is competition-dependent, cue-independent and reliant on prefrontal control: Silencing the medial prefrontal cortex with muscimol abolishes the effect. cFos imaging reveals that prefrontal control demands decline over repeated retrievals as competing memories are forgotten successfully, revealing a key adaptive benefit of forgetting. Occurring in 88% of the rats studied, this finding establishes a robust model of how adaptive forgetting harmonizes memory with behavioral demands, permitting isolation of its circuit, cellular and molecular mechanisms.Fil: Bekinschtein, Pedro Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; ArgentinaFil: Weisstaub, Noelia V.. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Gallo, Francisco Tomás. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Renner, Maria. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Anderson, Michael C.. University of Cambridge; Estados Unido

5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex

Context-dependent memories may guide adaptive behavior relaying in previous experience while updating stored information through reconsolidation. Retrieval can be triggered by partial and shared cues. When the cue is presented, the most relevant memory should be updated. In a contextual version of the object recognition task, we examined the effect of medial PFC (mPFC) serotonin 2a receptor (5-HT2aR) blockade during retrieval in reconsolidation of competing objects memories. We found that mPFC 5-HT2aR controls retrieval and reconsolidation of object memories in the perirhinal cortex (PRH), but not in the dorsal hippocampus in rats. Also, reconsolidation of objects memories in PRH required a functional interaction between the ventral hippocampus and the mPFC. Our results indicate that in the presence of conflicting information at retrieval, mPFC 5-HT2aR may facilitate top-down context-guided control over PRH to control the behavioral response and object memory reconsolidation.Fil: Morici, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Miranda, Magdalena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Gallo, Francisco Tomás. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Zanoni Saad, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad Favaloro; ArgentinaFil: Bekinschtein, Pedro Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Weisstaub, Noelia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Neurophotonics Approaches for the Study of Pattern Separation

Successful memory involves not only remembering over time but also keeping memories distinct. Computational models suggest that pattern separation appears as a highly efficient process to discriminate between overlapping memories. Furthermore, lesion studies have shown that the dentate gyrus (DG) participates in pattern separation. However, these manipulations did not allow identifying the neuronal mechanism underlying pattern separation. The development of different neurophotonics techniques, together with other genetic tools, has been useful for the study of the microcircuit involved in this process. It has been shown that less-overlapped information would generate distinct neuronal representations within the granule cells (GCs). However, because glutamatergic or GABAergic cells in the DG are not functionally or structurally homogeneous, identifying the specific role of the different subpopulations remains elusive. Then, understanding pattern separation requires the ability to manipulate a temporal and spatially specific subset of cells in the DG and ideally to analyze DG cells activity in individuals performing a pattern separation dependent behavioral task. Thus, neurophotonics and calcium imaging techniques in conjunction with activity-dependent promoters and high-resolution microscopy appear as important tools for this endeavor. In this work, we review how different neurophotonics techniques have been implemented in the elucidation of a neuronal network that supports pattern separation alone or in combination with traditional techniques. We discuss the limitation of these techniques and how other neurophotonic techniques could be used to complement the advances presented up to this date.Fil: Morales, Cristian. Pontificia Universidad Católica de Chile; ChileFil: Morici, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Miranda, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Gallo, Francisco Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Bekinschtein, Pedro Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Weisstaub, Noelia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentin

Dopamine Modulates Adaptive Forgetting in Medial Prefrontal Cortex

Active forgetting occurs in many species, but how behavioral control mechanisms influence which memories are forgotten remains unknown. We previously found that when rats need to retrieve a memory to guide exploration, it reduces later retention of other competing memories encoded in that environment. As with humans, this retrieval-induced forgetting relies on prefrontal control processes. Dopaminergic input to the prefrontal cortex is important for executive functions and cognitive flexibility. We found that, in a similar way, retrieval-induced forgetting of competing memories in male rats requires prefrontal dopamine signaling through D1 receptors. Blockade of medial prefrontal cortex D1 receptors as animals encountered a familiar object impaired active forgetting of competing object memories as measured on a later long-term memory test. Inactivation of the ventral tegmental area produced the same pattern of behavior, a pattern that could be reversed by concomitant activation of prefrontal D1 receptors. We observed a bidirectional modulation of retrieval-induced forgetting by agonists and antagonists of D1 receptors in the medial prefrontal cortex. These findings establish the essential role of prefrontal dopamine in the active forgetting of competing memories, contributing to the shaping of retention in response to the behavioral goals of an organism.Fil: Gallo, Francisco Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Zanoni Saad, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Silva, Azul. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Morici, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Miranda, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Anderson, Michael C.. University of Cambridge; Estados UnidosFil: Weisstaub, Noelia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Bekinschtein, Pedro Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Tourist loyalty and intangible cultural heritage: the case of Popayán, Colombia

The purpose of this paper is to analyse the loyalty of the tourists who visit a city with an important heritage event: The Holy Week Processions in the city of Popayán (Colombia), recognised by UNESCO as Intangible Cultural Heritage. Design/methodology/approach – This research focuses on determining the mediating effect of the perception of the processions and the evaluation of the elements of the destination during a visit to the city by using a sample of 615 tourists. The software tool used in this research is the Smart partial least squares. Findings – Results show that the motivations of the visitor are not enough by themselves to guarantee loyalty regarding the destination, but other variables are needed such as the perception of the processions and the evaluation of the elements of the destination, through which the motivation acquires a true meaning to secure the tourist’s loyalty. Practical implications – The principal practical implication of this research is offering to the stakeholders involved in the promotion and organisation of this event an opportunity to undertake and review actions for improvement. Originality/value – This research seeks to enlighten the interaction between heritage, sustainability and heritage in Latin America

Tourist segmentation in an intangible heritage setting: the Holy Week processions in the city of Popayán, Colombia

This research intends to establish a characterisation of the tourists who attend a representation that has been recognised as intangible cultural heritage by UNESCO, specifically, the Holy Week processions in the city of Popayán, Colombia. To achieve this goal, segmentation we conducted on the basis of two models that are widely used in the segmentation of tourists in World Heritage Sites: the McKercher model, based on cultural motivations, and Poria, Butler, and Airey’s model, based on the emotional perception of the visited heritage. Within this segmentation, there are four underlying types of visitors: incidental cultural, sightseeing cultural, serendipitous cultural and purposeful cultural tourists. The results show that there are three motivational dimensions among tourists who attend the Holy Week processions in the city of Popayán: hedonic, cultural, and convenience. The innovation of this research is, therefore, to reinforce the validation of types of tourists in the literature on Word Heritage Site destinations but, in this case, we apply it to an intangible cultural heritage resource in Latin America

Infant gut microbiota contributes to cognitive performance in mice

Work in the author’s laboratories was performed on resources provided by the Spanish Health and Science Ministries (PREOBE project P06-CTS-02341, BFU2012-40254-C03-01, and PID2020-114269GB-I00), Junta de Andalucía, and UFZ-Germany. T.C. participated in the PhD program in biomedicine at UGR, was a fellowship of the FPI program (BES-2013-065133) funded by the Spanish Ministry of Economy and Competitiveness, and is currently supported by the ‘‘Sara Borrell’’ program (CD21/00187) of the Carlos III Institute. I.A., S.M.-M., and A.R.-R. were granted PhD scholarships (FPU) from the Spanish Ministry of Economy and Competitiveness. A.R.-R. currently holds a María Zambrano Next Generation EU-Talent Reincorporation from UGR.Gut microbiota has been related to infant neurodevelopment. Here, an association between infant composite cognition with gut microbiota composition was established as soon as 6 months. Higher diversity and evenness characterized microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses established an association between microbial histidine ammonia lyase activity and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice showed that memory, assessed by novel object recognition test, was a transmissible trait. Furthermore, Inf-aboveCC mice were enriched in species previously linked to cognition belonging to Bacteroides, Phaeicola and Bifidobacterium. Finally, Inf-aboveCC mice showed differential faecal histidine, hippocampal urocanate and histidine-urocanate-glutamate ratios compared to Inf-aboveCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition pointing at modulation of histidine metabolite levels as a potential underlying mechanism.Spanish Health and Science Ministries (PREOBE project P06-CTS-02341, BFU2012-40254-C03-01, PID2020-114269GB-I00)Junta de AndalucíaUFZ-GermanySpanish Ministry of Economy and Competitiveness BES-2013-065133Carlos III Institute (CD21/00187)María Zambrano Next Generation EU-Talent ReincorporationUG

Pediatric extremity bone sarcoma reconstruction with the vascularized fibula flap: Observational study assessing long-term functional outcomes, complications, and survival

[Background] Limb salvage is important in pediatric patients with bone sarcomas. The vascularized fibula flap is a versatile option, combined or not with a bone allograft. The authors evaluated the functional long-term outcomes, complications, and survival of using this technique in pediatric patients.[Methods] A retrospective review of 27 pediatric patients reconstructed between 2011 and 2018 with the fibula flap after bone sarcoma resection was conducted. Long-term functional outcomes, complications, and survival were assessed. Variables analyzed were age, sex, Capanna technique, follow-up, complications, additional surgeries, time to weight bearing, length discrepancy, and sport practice. r functional recovery are expected in patients below the age of 8 years.[Results] Twenty-seven patients with a mean age of 9.3 years were included. The mean follow-up was 44.33 months. The Capanna technique was performed in 15 patients. All extremities but one were salvaged. The overall complication rate was 74.07%. Fibula fracture and nonunion rates were 34.04% and 11.11%, respectively. Partial weight bearing was resumed at a mean of 9.07 months. About 79.17% of patients with a 12-month follow-up achieved full weight bearing. An age below 8 years was significantly associated with a lower major complication rate and a shorter time to weight bearing and full weight bearing. Major complications and additional surgeries were significantly associated with longer periods until weight bearing and full weight bearing.[Conclusions] The fibula flap allows the majority of extremities to be reconstructed. However, a high rate of complications and additional surgeries should be anticipated. Full weight bearing is usually achieved within the first year, with modest functional increase afterward. Less complications and a faster functional recovery are expected in patients below the age of 8 years.Funding was received from the Spanish public institution Carlos III Health Institute for the accomplishment of this study, center affiliated to the Spanish Ministry of Economy, Industry and Competitiveness, as part of the Research in Healthcare Program (Reference number PI16/01447).Peer reviewe