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The reliance on student samples has long been a subject of debate in experimental approaches to studying behaviour. We contribute to this discussion by looking at differences in financial behaviour between a student and a non-student sample in three sets of lab experiments conducted in Spain, Germany and Poland (n=857). Participants from both samples switched more often and made better financial decisions after they received a message encouraging them to switch financial service providers. While the size of the effect on switching frequency was comparable between the two samples, the effect on switching quality was significantly stronger on non-students. Further analysis suggests this is due to a better performance of students before the prompt leaving less room for improvement by the reminder. Results suggest that experimental evidence derived from students should be generalized with caution.
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Harmful algal blooms and the toxins produced during these events are a human and environmental health concern worldwide. Saxitoxin and its derivatives are potent natural aquatic neurotoxins produced by certain freshwater cyanobacteria and marine algae species during these bloom events. Saxitoxins effects on human health are well studied, however its effects on aquatic biota are still largely unexplored. This work aims at evaluating the effects of a pulse acute exposure (24 h) of the model cladoceran Daphnia magna to 30 µg saxitoxin L-1, which corresponds to the safety guideline established by the World Health Organization (WHO) for these toxins in recreational freshwaters. Saxitoxin effects were assessed through a comprehensive array of biochemical (antioxidant enzymes activity and lipid peroxidation), genotoxicity (alkaline comet assay), neurotoxicity (total cholinesterases activity), behavioral (swimming patterns), physiological (feeding rate and heart rate), and epigenetic (total 5-mC DNA methylation) biomarkers. Exposure resulted in decreased feeding rate, heart rate, total cholinesterases activity and catalase activity. Contrarily, other antioxidant enzymes, namely glutathione-S-transferases and selenium-dependent Glutathione peroxidase had their activity increased, together with lipid peroxidation levels. The enhancement of the antioxidant enzymes was not sufficient to prevent oxidative damage, as underpinned by lipid peroxidation enhancement. Accordingly, average DNA damage level was significantly increased in STX-exposed daphnids. Total DNA 5-mC level was significantly decreased in exposed organisms. Results showed that even a short-term exposure to saxitoxin causes significant effects on critical molecular and cellular pathways and modulates swimming patterns in D. magna individuals. This study highlights sub-lethal effects caused by saxitoxin in D. magna, suggesting that these toxins may represent a marked challenge to their thriving even at a concentration deemed safe for humans by the WHO.
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In the mammalian neocortex, GABAergic interneurons (INs) inhibit cortical networks in profoundly different ways. The extent to which this depends on how different INs process excitatory signals along their dendrites is poorly understood. Here, we reveal that the functional specialization of two major populations of cortical INs is determined by the unique association of different dendritic integration modes with distinct synaptic organization motifs. We found that somatostatin (SST)-INs exhibit NMDAR-dependent dendritic integration and uniform synapse density along the dendritic tree. In contrast, dendrites of parvalbumin (PV)-INs exhibit passive synaptic integration coupled with proximally enriched synaptic distributions. Theoretical analysis shows that these two dendritic configurations result in different strategies to optimize synaptic efficacy in thin dendritic structures. Yet, the two configurations lead to distinct temporal engagement of each IN during network activity. We confirmed these predictions with in vivo recordings of IN activity in the visual cortex of awake mice, revealing a rapid and linear recruitment of PV-INs as opposed to a long-lasting integrative activation of SST-INs. Our work reveals the existence of distinct dendritic strategies that confer distinct temporal representations for the two major classes of neocortical INs and thus dynamics of inhibition.
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Dear Editor, According to GINA, severe asthma is defined as uncontrolled asthma, despite therapy adherence with an optimized high dose of inhaled corticosteroid plus long-acting ß2-agonist coupled with management of modifiable factors/comorbidities, that worsens when this treatment is decreased. It affects a significant portion of asthmatic patients and imposes a high risk of exacerbations and mortality, which are associated with significant healthcare costs and psychosocial impact...
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Musculoskeletal (MSK) injuries have a significant physical and psychological influence on an athlete's life. A systematic review of prospective cohort, cross-sectional, and case-control studies was undertaken in this study to analyze the association between MSK injuries with depressive symptoms in athletes. We searched on PubMed, Web of Science, and Scopus, with data inception to 15 February 2023. The methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Of the 3677 potential studies only nine were included. These studies showed a bidirectional association between MSK injuries and depressive symptoms. Athletes with MSK injuries had higher levels of depressive symptoms, which raises the likelihood of experiencing depression in the future. Women athletes had higher levels of depressive symptoms compared with men. The presence of depressive symptoms is a significant predictor of disability in athletes. Our findings suggest that coaches should be more aware of depressive symptoms, in order to prevent MSK injuries, and to monitor athletes following an MSK injury.
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Traumatismos en Atletas , Enfermedades Musculoesqueléticas , Masculino , Humanos , Femenino , Depresión/epidemiología , Estudios Prospectivos , Estudios Transversales , Atletas/psicología , Traumatismos en Atletas/psicologíaRESUMEN
Naturally occurring radioactive materials (NORM) contribute to the dose arising from radiation exposure for workers, public and non-human biota in different working and environmental conditions. Within the EURATOM Horizon 2020 RadoNorm project, work is ongoing to identify NORM exposure situations and scenarios in European countries and to collect qualitative and quantitative data of relevance for radiation protection. The data obtained will contribute to improved understanding of the extent of activities involving NORM, radionuclide behaviours and the associated radiation exposure, and will provide an insight into related scientific, practical and regulatory challenges. The development of a tiered methodology for identification of NORM exposure situations and complementary tools to support uniform data collection were the first activities in the mentioned project NORM work. While NORM identification methodology is given in Michalik et al., 2023, in this paper, the main details of tools for NORM data collection are presented and they are made publicly available. The tools are a series of NORM registers in Microsoft Excel form, that have been comprehensively designed to help (a) identify the main NORM issues of radiation protection concern at given exposure situations, (b) gain an overview of materials involved (i.e., raw materials, products, by-products, residues, effluents), c) collect qualitative and quantitative data on NORM, and (d) characterise multiple hazards exposure scenarios and make further steps towards development of an integrated risk and exposure dose assessment for workers, public and non-human biota. Furthermore, the NORM registers ensure standardised and unified characterisation of NORM situations in a manner that supports and complements the effective management and regulatory control of NORM processes, products and wastes, and related exposures to natural radiation worldwide.
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Exposición a la Radiación , Monitoreo de Radiación , Protección Radiológica , Radiactividad , Radioisótopos/análisis , Europa (Continente)RESUMEN
This study's aim was two-fold: (i) to test the intra-session reliability of the one-leg balance activity test; and (ii) to assess the influence of age on reaction time (RT) and the differences between dominant and non-dominant feet. Fifty young soccer players with an average age of 12.4 ± 1.8 years were divided into two groups: younger soccer players (n = 26; 11.6 ± 0.9 years) and older soccer players (n = 24; 14.2 ± 0.8 years). Each group then completed four trials (two with each leg) of the one-leg balance activity (OLBA) to evaluate RT under a single-leg stance. Mean RT and the number of hits were calculated, and the best trial was also selected. T-tests and Pearson correlations were performed for statistical analysis. Values for RT were lower, and the number of hits was higher while standing on the non-dominant foot (p = 0.01). MANOVA revealed that the "Dominant Leg" factor did not affect the multivariate composite (Pillai Trace = 0.05; F(4, 43) = 0.565; p = 0.689; Partial ETA Squared = 0.050; Observed Power = 0.174). The "Age" factor did not present an effect on the multivariate composite (Pillai Trace = 0.104; F(4, 43) = 1.243; p = 0.307; Partial ETA Squared = 0.104; Observed Power = 0.355). The results of the present investigation demonstrate that RT may be lower while standing on the non-dominant foot.
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Naturally occurring radioactive materials (NORM) are present worldwide and under certain circumstances (e.g., human activities) may give radiation exposure to workers, local public or occasional visitors and non-human biota (NHB) of the surrounding ecosystems. This may occur during planned or existing exposure situations which, under current radiation protection standards, require identification, management, and regulatory control as for other practices associated with man-made radionuclides that may result in the exposure of people and NHB. However, knowledge gaps exist with respect to the extent of global and European NORM exposure situations and their exposure scenario characteristics, including information on the presence of other physical hazards, such as chemical and biological ones. One of the main reasons for this is the wide variety of industries, practices and situations that may utilise NORM. Additionally, the lack of a comprehensive methodology for identification of NORM exposure situations and the absence of tools to support a systematic characterisation and data collection at identified sites may also lead to a gap in knowledge. Within the EURATOM Horizon 2020 RadoNorm project, a methodology for systematic NORM exposure identification has been developed. The methodology, containing consecutive tiers, comprehensively covers situations where NORM may occur (i.e., minerals and raw materials deposits, industrial activities, industrial products and residues and their applications, waste, legacies), and thus, allows detailed investigation and complete identification of situations where NORM may present a radiation protection concern in a country. Details of the tiered methodology, with practical examples on harmonised data collection using a variety of existing sources of information to establish NORM inventories, are presented in this paper. This methodology is flexible and thus applicable to a diversity of situations. It is intended to be used to make NORM inventory starting from the scratch, however it can be used also to systematise and complete existing data.
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Exposición a la Radiación , Monitoreo de Radiación , Protección Radiológica , Residuos Radiactivos , Humanos , Ecosistema , Radioisótopos/análisis , Unión Europea , Residuos Radiactivos/análisisRESUMEN
Microbial metabolomics allows understanding and to comprehensively analyse metabolites, and their related cellular and metabolic processes, that are produced and released to the extracellular environment under specific conditions. In that regard, the main objective of this research is to understand the impact of culture media changes in the metabolic profile of Pedobacter lusitanus NL19 (NL19) and Pedobacter himalayensis MTCC 6384 (MTCC6384) and respective influence on the production of biotechnologically relevant compounds. Solid-phase microextraction combined with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry with time-of-flight analyser (GC × GC-ToFMS) was applied to comprehensively study the metabolites produced by NL19 and MTCC6384 both in tryptic soy broth 100% (TSB100) and tryptic soy broth with 25% casein peptone (PC25). A total of 320 metabolites were putatively identified, which belong to different chemical families: alcohols, aldehydes, esters, ethers, hydrocarbons, ketones, nitrogen compounds, sulphur compounds, monoterpenes, and sesquiterpenes. Metabolites that were statistically different from the control (sterile medium) were selected allowing for the construction of the metabolic profile of both strains. A set of 80 metabolites was tentatively associated to the metabolic pathways such as the metabolism of fatty acids, branched-chain aminoacids, phenylalanine, methionine, aromatic compounds, and monoterpene and sesquiterpene biosynthesis. This study allowed to better understand how slight changes of the culture media and thus the composition of nutrients impair the metabolic profile of bacteria, which may be further explored for metabolomics pipeline construction or biotechnological applications.
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Aldehídos , Compuestos Orgánicos Volátiles , Humanos , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectrometría de Masas , Monoterpenos , Medios de Cultivo , Compuestos Orgánicos Volátiles/química , Microextracción en Fase Sólida/métodosRESUMEN
In the neocortex, fast synaptic inhibition orchestrates both spontaneous and sensory-evoked activity. GABAergic interneurons (INs) inhibit pyramidal neurons (PNs) directly, modulating their output activity and thus contributing to balance cortical networks. Moreover, several IN subtypes also inhibit other INs, forming specific disinhibitory circuits, which play crucial roles in several cognitive functions. Here, we studied a subpopulation of somatostatin-positive INs, the Martinotti cells (MCs) in layer 2/3 of the mouse barrel cortex (both sexes). MCs inhibit the distal portion of PN apical dendrites, thus controlling dendrite electrogenesis and synaptic integration. Yet, it is poorly understood whether MCs inhibit other elements of the cortical circuits, and the connectivity properties with non-PN targets are unknown. We found that MCs have a strong preference for PN dendrites, but they also considerably connect with parvalbumin-positive, vasoactive intestinal peptide-expressing, and layer 1 (L1) INs. Remarkably, GABAergic synapses from MCs exhibited clear cell type-specific short-term plasticity. Moreover, whereas the biophysical properties of MC-PN synapses were consistent with distal dendritic inhibition, MC-IN synapses exhibited characteristics of fast perisomatic inhibition. Finally, MC-PN connections used α5-containing GABAA receptors (GABAARs), but this subunit was not expressed by the other INs targeted by MCs. We reveal a specialized connectivity blueprint of MCs within different elements of superficial cortical layers. In addition, our results identify α5-GABAARs as the molecular fingerprint of MC-PN dendritic inhibition. This is of critical importance, given the role of α5-GABAARs in cognitive performance and their involvement in several brain diseases.SIGNIFICANCE STATEMENT Martinotti cells (MCs) are a prominent, broad subclass of somatostatin-expressing GABAergic interneurons, specialized in controlling distal dendrites of pyramidal neurons (PNs) and taking part in several cognitive functions. Here we characterize the connectivity pattern of MCs with other interneurons in the superficial layers (L1 and L2/3) of the mouse barrel cortex. We found that the connectivity pattern of MCs with PNs as well as parvalbumin, vasoactive intestinal peptide, and L1 interneurons exhibit target-specific plasticity and biophysical properties. The specificity of α5-GABAARs at MC-PN synapses and the lack or functional expression of this subunit by other cell types define the molecular identity of MC-PN connections and the exclusive involvement of this inhibitory circuits in α5-dependent cognitive tasks.
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Parvalbúminas , Péptido Intestinal Vasoactivo , Femenino , Masculino , Animales , Péptido Intestinal Vasoactivo/metabolismo , Parvalbúminas/metabolismo , Neuronas , Células Piramidales/fisiología , Interneuronas/fisiología , Somatostatina/metabolismo , Sinapsis/fisiología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Perisomatic inhibition of pyramidal neurons (PNs) coordinates cortical network activity during sensory processing, and this role is mainly attributed to parvalbumin-expressing basket cells (BCs). However, cannabinoid receptor type 1 (CB1)-expressing interneurons are also BCs, but the connectivity and function of these elusive but prominent neocortical inhibitory neurons are unclear. We find that their connectivity pattern is visual area specific. Persistently active CB1 signaling suppresses GABA release from CB1 BCs in the medial secondary visual cortex (V2M), but not in the primary visual cortex (V1). Accordingly, in vivo, tonic CB1 signaling is responsible for higher but less coordinated PN activity in the V2M than in the V1. These differential firing dynamics in the V1 and V2M can be captured by a computational network model that incorporates visual-area-specific properties. Our results indicate a differential CB1-mediated mechanism controlling PN activity, suggesting an alternative connectivity scheme of a specific GABAergic circuit in different cortical areas.
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Endocannabinoides , Neocórtex , Interneuronas/fisiología , Neuronas/fisiología , Células Piramidales/fisiología , Receptor Cannabinoide CB1 , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
GluN3A is an atypical glycine-binding subunit of NMDA receptors (NMDARs) whose actions in the brain are mostly unknown. Here, we show that the expression of GluN3A subunits controls the excitability of mouse adult cortical and amygdalar circuits via an unusual signaling mechanism involving the formation of excitatory glycine GluN1/GluN3A receptors (eGlyRs) and their tonic activation by extracellular glycine. eGlyRs are mostly extrasynaptic and reside in specific neuronal populations, including the principal cells of the basolateral amygdala (BLA) and SST-positive interneurons (SST-INs) of the neocortex. In the BLA, tonic eGlyR currents are sensitive to fear-conditioning protocols, are subject to neuromodulation by the dopaminergic system, and control the stability of fear memories. In the neocortex, eGlyRs control the in vivo spiking of SST-INs and the behavior-dependent modulation of cortical activity. GluN3A-containing eGlyRs thus represent a novel and widespread signaling modality in the adult brain, with attributes that strikingly depart from those of conventional NMDARs.
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Amígdala del Cerebelo , Neocórtex , Receptores de Glicina , Receptores de N-Metil-D-Aspartato , Amígdala del Cerebelo/metabolismo , Animales , Corteza Cerebral/metabolismo , Glicina/metabolismo , Interneuronas/metabolismo , Ratones , Neocórtex/metabolismo , Neuronas/metabolismo , Receptores de Glicina/genética , Receptores de Glicina/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
With the COVID-19 outbreak, schools have experienced difficulty providing moderate-to-vigorous physical activity (MVPA) to their students, which should normally account for at least 50% of children's physical education (PE) class time. We aimed to determine the intensity of physical activity (PA) within PE classes at various grade levels to compare children's in-class PA with the World Health Organization's (WHO) recommended guidelines. Thus, 301 students (1st to 12th grade) participated in the investigation. Children were evaluated during the PE classes with different typologies and durations. We assessed PA intensity using accelerometry and grouped data into either sedentary-to-light PA (SEDLI) or MVPA. Each child was assessed using both the time spent in PA (hours:minutes:seconds) and the percentage of time spent in PA versus other class activities. We found that, in the second-grade level group (fifth and sixth grades), girls spent more time in MVPA intensity than boys. Additionally, two-hour PE classes doubled the SEDLI for students in the third-grade group, and polythematic classes (those with more than one sport) promoted more MVPA level time than monothematic classes (only one sport). Concerning PA intensity during PE classes, 31-43% of the PE class total time was spent in MVPA but presented short duration and did not usually persist for 10 consecutive minutes (59% of the time). Children spent a large amount of time at the SEDLI intensity, considered insufficient for PA health benefits. Finally, to meet WHO guidelines for PA intensity, PE classes will need to increase MVPA time and reduce non-active periods between activities.
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COVID-19 , Educación y Entrenamiento Físico , Acelerometría , COVID-19/epidemiología , Niño , Ejercicio Físico , Femenino , Humanos , Masculino , Pandemias , Instituciones AcadémicasRESUMEN
Lantibiotics are a promising class of natural antimicrobial peptides. Lichenicidin is a two-peptide lantibiotic in which two mature peptides act synergistically to exhibit full bioactivity. Considering the two-peptide lantibiotics described so far, only cytolysin has been deeply characterized in terms of toxicity towards eukaryotic cells and it was found to be hemolytic and cytotoxic. This work aimed to improve the production of lichenicidin in vivo and characterize its antibacterial activity and toxicity against human cells. Peptides were purified and minimal inhibitory concentration (MIC) was determined against several strains; a time-kill assay was performed with Staphylococcus aureus. The hemolytic effect of lichenicidin was evaluated on blood samples from healthy donors and its toxicity towards human fibroblasts. The quantity of purified peptides was 1 mg/l Bliα and 0.4 mg/l Bliß. MIC for methicillin-sensitive and resistant S. aureus (MSSA and MRSA) strains were 16-32 µg/ml and 64-128 µg/ml, respectively. At the MIC, lichenicidin took less than 3 h to eliminate MSSA, indicating a strong bactericidal effect. It induces cell lysis at the highest concentration, an effect that might be potentiated by Bliß. Lichenicidin was not cytotoxic to human erythrocytes and fibroblasts. In this work, we evaluated the therapeutic potential of lichenicidin as a possible antimicrobial alternative.
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Antiinfecciosos/farmacología , Péptidos Antimicrobianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Bacteriocinas/farmacología , Fibroblastos/efectos de los fármacos , Péptidos/farmacología , Secuencia de Aminoácidos , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Péptidos Antimicrobianos/aislamiento & purificación , Bacteriocinas/química , Bacteriocinas/aislamiento & purificación , Línea Celular , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Hemólisis , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Empathy is the capacity to understand and resonate with the experiences of other people. Patient enablement is the degree to which a patient feels strengthened in terms of being able to deal with, understand and manage their disease. METHODS: Secondary cross-sectional analysis of existing data from 2 independent datasets (456 primary health care patients), with the application of two validated questionnaires, Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE) and Patient Enablement Instrument (PEI). OBJECTIVE: Evaluate medical empathy and patients' enablement after consultation with their family doctors and to verify if there was an association between these two concepts. RESULTS: The median value of JSPPPE-VP score was 6.60 (interquartile range 1.00) and of PEI/ICC score was of 1.83 (interquartile range 0.67). Regarding empathy (JSPPPE-VP), patients taking chronic medication had a slight but significantly higher median score than patients not taking them (6.70 versus 6.60, P = 0.049), although regression modelling did not confirm any relevant predictor of JSPPPE-VP score. Regarding enablement (PEI/ICC), we found significantly higher scores on younger patients, as well as, on more educated and professionally active ones (P < 0.001). Multivariable linear regression and Poisson regression modelling confirmed such variables as statistically significant potential predictors. CONCLUSIONS: A significant positive association was found between empathy score (JSPPPE-VP) and enablement score (PEI/ICC), when adjusted to sociodemographic cofactors. On this linear regression model, age category and educational level were also significantly associated with empathy score, with the same pattern found on bivariate analysis.
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Empatía , Médicos , Estudios Transversales , Humanos , Satisfacción del Paciente , Relaciones Médico-Paciente , Portugal , Atención Primaria de Salud , Encuestas y CuestionariosRESUMEN
Novel natural products are urgently needed to address the worldwide incidence of bacterial resistance to antibiotics. Extreme environments are a major source of novel compounds with unusual chemical structures. Pedobacter lusitanus NL19 is a new bacterial species that was isolated from one such environment and which produces compounds with potent activity against relevant microorganisms in the clinical, food, veterinary and aquaculture areas. The production of antimicrobials by P. lusitanus NL19 was identified in tryptic soy agar (TSA), but not in its equivalent broth (TSB). It was observed that in TSB medium a high concentration of casein peptone (PC) repressed the production of antibacterial compounds. HPLC, MS and MS/MS spectra with de novo sequencing revealed that the bioactivity of P. lusitanus NL19 was due to the production of pedopeptins. Hence, biosynthesis of pedopeptins is inhibited by high concentrations of PC in the broth medium. Furthermore, a nonribosomal peptide synthetase (NRPS) gene cluster was identified in the genome of NL19 encoding the biosynthesis of the peptides. qPCR analysis confirmed that the transcription of these genes is repressed in cells cultivated in high concentrations of PC. It is shown that pedopeptins are nonribosomal peptides with a broad-spectrum activity, including against Gram-positive and Gram-negative bacteria and yeasts.
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Caseínas/química , Pedobacter/química , Péptidos Cíclicos/antagonistas & inhibidores , Peptonas/metabolismo , Estructura Molecular , Pedobacter/metabolismo , Péptidos Cíclicos/biosíntesis , Péptidos Cíclicos/química , Peptonas/químicaRESUMEN
The neocortex plays a crucial role in all basic and abstract cognitive functions. Conscious mental processes are achieved through a correct flow of information within and across neocortical networks, whose particular activity state results from a tight balance between excitation and inhibition. The proper equilibrium between these indissoluble forces is operated with multiscale organization: along the dendro-somatic axis of single neurons and at the network level. Fast synaptic inhibition is assured by a multitude of inhibitory interneurons. During cortical activities, these cells operate a finely tuned division of labor that is epitomized by their detailed connectivity scheme. Recent results combining the use of mouse genetics, cutting-edge optical and neurophysiological approaches have highlighted the role of fast synaptic inhibition in driving cognition-related activity through a canonical cortical circuit, involving several major interneuron subtypes and principal neurons. Here we detail the organization of this cortical blueprint and we highlight the crucial role played by different neuron types in fundamental cortical computations. In addition, we argue that this canonical circuit is prone to many variations on the theme, depending on the resolution of the classification of neuronal types, and the cortical area investigated. Finally, we discuss how specific alterations of distinct inhibitory circuits can underlie several devastating brain diseases.
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Neocórtex , Animales , Inhibición Psicológica , Interneuronas , Ratones , Inhibición Neural , Neuronas , NeurofisiologíaRESUMEN
Down syndrome (DS) results in various degrees of cognitive deficits. In DS mouse models, recovery of behavioral and neurophysiological deficits using GABAAR antagonists led to hypothesize an excessive activity of inhibitory circuits in this condition. Nonetheless, whether over-inhibition is present in DS and whether this is due to specific alterations of distinct GABAergic circuits is unknown. In the prefrontal cortex of Ts65Dn mice (a well-established DS model), we found that the dendritic synaptic inhibitory loop formed by somatostatin-positive Martinotti cells (MCs) and pyramidal neurons (PNs) was strongly enhanced, with no alteration in their excitability. Conversely, perisomatic inhibition from parvalbumin-positive (PV) interneurons was unaltered, but PV cells of DS mice lost their classical fast-spiking phenotype and exhibited increased excitability. These microcircuit alterations resulted in reduced pyramidal-neuron firing and increased phase locking to cognitive-relevant network oscillations in vivo. These results define important synaptic and circuit mechanisms underlying cognitive dysfunctions in DS.
Down syndrome is a genetic disorder caused by the presence of a third copy of chromosome 21. Affected individuals show delayed growth, characteristic facial features, altered brain development; with mild to severe intellectual disability. The exact mechanisms underlying the intellectual disability in Down syndrome are unclear, although studies in mice have provided clues. Drugs that reduce the inhibitory activity in the brain improve cognition in a mouse model of Down syndrome. This suggests that excessive inhibitory activity may contribute to the cognitive impairments. Many different neural circuits generate inhibitory activity in the brain. These circuits contain cells called interneurons. Sub-types of interneurons act via different mechanisms to reduce the activity of neurons. Identifying the interneurons that are affected in Down syndrome would thus improve our understanding of the brain basis of the disorder. Zorrilla de San Martin et al. compared mice with Down syndrome to unaffected control mice. The results revealed an increased activity in two types of inhibitory brain circuits in Down syndrome. The first contains interneurons called Martinotti cells. These help the brain to combine inputs from different sources. The second contains interneurons called parvalbumin-positive basket cells. These help different areas of the brain to synchronize their activity, which in turn makes it easier for those areas to exchange information. By mapping the changes in inhibitory circuits in Down syndrome, Zorrilla de San Martin et al. have provided new insights into the biological basis of the disorder. Future studies should examine whether targeting specific circuits with pharmacological treatments could ultimately help reduce the associated impairments.
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Síndrome de Down/fisiopatología , Interneuronas/metabolismo , Parvalbúminas/metabolismo , Corteza Prefrontal/fisiopatología , Células Piramidales/metabolismo , Somatostatina/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , RatonesRESUMEN
Flash glucose monitoring system (FGMS) is an improved subset of continuous glucose monitoring with a recognized effectiveness on glycemic control, though validation in patients with Liver Cirrhosis (LC) is lacking. To evaluate the accuracy of FGMS in patients with Type 2 Diabetes Mellitus (DM) and LC, a prospective, case-control study was performed in 61 ambulatory patients with LC and DM (LC group, n = 31) or DM (Control group, n = 30). During 14 days, patients performed 4 assessments per day of self-monitoring of blood glucose (SMBG, reference value) followed by FGMS scanning. There were 2567 paired SMBG and FGMS values used in the accuracy analysis, with an overall mean absolute relative difference (MARD) of 12.68% in the LC group and 10.55% in the control group (p < 0,001). In patients with LC, the percentage of readings within Consensus Consensus Error Grid analysis Zone A and A + B were 80.36% and 99,26%, respectively. Sensor clinical accuracy was not affected by factors such as body mass index, age, gender, Child-Pugh score or edematoascitic decompensation. This is the first study to approach FGMS clinical accuracy in LC, revealing a potential usability of this system to monitor glycemic control in this population.