Search Results (60)

Objectives: Females are often underrepresented in preclinical fear research due to concerns over estrous cycle related variability. This study examined whether there were differences between female and male C57BL/6J mice in terms of fear extinction and safety learning, aiming to verify the inclusion of both sexes in fear regulation research. Methods: Mice underwent a 5-day fear conditioning and extinction protocol, with recent (Day 6) and remote (Day 13) retrieval tests. A separate cohort received unpaired tone-shock safety conditioning over two days, followed by recent and remote retrieval. Freezing percentage and locomotor distance, among other measures, were quantified to compare behavioral responses between sexes. Results: During fear acquisition and extinction, females and males showed comparable conditioned fear and progressive extinction, with no sex differences in freezing percentage, bout counts, or locomotor distance. Freezing remained low during both recent and remote retrieval in both sexes. In the safety-conditioning task, the safety cue reduced freezing relative to contextual baseline, contextual freezing declined from recent to remote retrieval, and no sex differences were observed across measures. Conclusions: Female and male C57BL/6J mice exhibit equivalent performance in auditory fear conditioning, extinction, retrieval, and safety learning under matched conditions. These findings support equitable inclusion of both sexes in preclinical fear-regulation studies, enhancing translational relevance without added behavioral variability. Full article

Staphylococcus epidermidis is more often known as a human skin commensal, serving as a primary protective bacterium on the skin’s surface. However, more recent literature highlights the role of S. epidermidis as a nosocomial pathogen and a multidrug-resistant organism that poses a global threat. The evolution of S. epidermidis can be owed to its accumulation of resistance mechanisms, including adhesion, biofilm formation, genomic islands, phage elements, integrated plasmids, and quorum sensing. It is suspected that through gene transfer, S. epidermidis is partially responsible for the feared multidrug-resistant Staphylococcus aureus through the mecA gene and many other genomic island transfers. Overall, prolonged nosocomial exposure and misuse of antibiotics have driven dramatic genomic remodeling in S. epidermidis, characterized by many methods of genetic recombination, SCCmec and insertion sequence acquisition, and accumulation of multiple resistance genes. Our review reviews the role of S. epidermidis as both a commensal and a pathogenic bacterium, summarizes the genes responsible for its multidrug resistance, and describes methods of combatting its invasion. Full article

This dataset provides synchronized multimodal behavioral measurements from 36 mice across four experimental groups: wild-type and rTg4510 tauopathy mice, each tested with or without doxycycline-mediated suppression of mutant tau expression. Of these, 34 mice had complete measurements across all three behavioral paradigms and were used for analyses requiring full cross-task linkage. At six months of age, all animals underwent three standardized behavioral paradigms: home cage monitoring, ten-day trace eyeblink conditioning, and contextual fear conditioning. The individual-level data included locomotor activity, rearing duration, conditioned response metrics, eyelid closure latencies, and contextual freezing percentages. All measurements were linked using unique mouse identifiers, enabling cross-task analysis without preprocessing or imputation. The dataset was accompanied by a complete data dictionary, processing workflow diagram, and validation analyses demonstrating cross-paradigm correlations. The cross-task associations are illustrated in the main figures, with additional early phase acquisition and temporal processing correlations provided in the main figures. Provided in an open CSV format with detailed metadata, this resource supports behavioral phenotyping, machine learning applications, and the investigation of learning mechanisms in tauopathy models. Full article

Emotional Footprint Identification refers to the process of recognizing or understanding the emotional impact that a person, experience, or interaction leaves on others. Emotion Recognition plays an important role in human–computer interaction for identifying emotions such as fear, sadness, anger, happiness, and surprise on the human face during the conversation. However, accurate emotional footprint identification plays a crucial role due to the dynamic changes. Conventional deep learning techniques integrate advanced technologies for emotional footprint identification, but challenges in accurately detecting emotions in minimal time. To address these challenges, a novel Divergence Shepherd Feature Optimization-based Stochastic-Tuned Deep Multilayer Perceptron (DSFO-STDMP) is proposed. The proposed DSFO-STDMP model consists of three distinct processes namely data acquisition, feature selection or reduction, and classification. First, the data acquisition phase collects a number of conversation data samples from a dataset to train the model. These conversation samples are given to the Sokal–Sneath Divergence shuffling shepherd optimization to select more important features and remove the others. This optimization process accurately performs the feature reduction process to minimize the emotional footprint identification time. Once the features are selected, classification is carried out using the Rosenthal correlative stochastic-tuned deep multilayer perceptron classifier, which analyzes the correlation score between data samples. Based on this analysis, the system successfully classifies different emotions footprints during the conversations. In the fine-tuning phase, the stochastic gradient method is applied to adjust the weights between layers of deep learning architecture for minimizing errors and improving the model’s accuracy. Experimental evaluations are conducted using various performance metrics, including accuracy, precision, recall, F1 score, and emotional footprint identification time. The quantitative results reveal enhancement in the 95% accuracy, 93% precision, 97% recall and 97% F1 score. Additionally, the DSFO-STDMP minimized the in training time by 35% when compared to traditional techniques. Full article

Introduction: Building a life in an asylum country poses specific challenges for women, who often face compounded barriers in healthcare, language acquisition, economic independence, childcare, education, cultural adaptation, and legal processes. This study examines the experiences of asylum-seeking women in Portugal, focusing on discrimination perpetrated by professionals within reception and integration institutions. Methods: Drawing on 24 semi-structured interviews with women from the Middle East (n = 14) and Africa (n = 10), this research adopts a criminological and gender lens and employs a narrative paradigm informed by constructivist Grounded Theory and an abductive approach. Results: The analysis reveals that institutional discrimination, manifested through neglect, hostility, and cultural insensitivity, reinforces feelings of abandonment and fear, obstructs integration, and perpetuates cycles of marginalization and vulnerability. These dynamics are intensified by gender-based and structural violence embedded in asylum procedures and professional practices. The findings highlight the emotional and relational dimensions of institutional encounters, showing how empathy, trust, and intercultural awareness among professionals are crucial for effective inclusion. Conclusions: This study concludes that addressing institutional discrimination requires systemic change, professional training in gender-sensitive and intercultural competencies, and the promotion of equitable, inclusive, and human rights-based reception practices in Portugal. Full article

Background: Hyperphosphorylated tau accumulation and neurofibrillary tangles (NFTs) are hallmarks of tauopathies, including Alzheimer’s disease (AD), and are strongly associated with cognitive decline. The rTg4510 mouse model, which expresses mutant human tau (P301L), develops progressive tauopathy in the absence of amyloid-β pathology, providing a valuable tool for investigating tau-driven neurodegeneration. Previous studies have demonstrated spatial and object-recognition memory deficits at six months of age, which can be prevented by doxycycline (DOX)-mediated suppression of tau expression. However, it remained unclear whether non-spatial hippocampal learning, particularly temporal associative learning, would be similarly affected. Methods: We evaluated six-month-old rTg4510 mice with or without DOX treatment. To control for potential motor confounds, we first assessed spontaneous home cage activity. We then tested hippocampus-dependent non-spatial learning using two paradigms: trace eyeblink conditioning (500-ms trace interval) and contextual fear conditioning. Results: General motor function remained intact; however, rTg4510 mice without DOX treatment exhibited increased rearing behavior. These mice demonstrated significant deficits in trace eyeblink conditioning acquisition, with particularly clear impairment on the final day of training. Contextual fear conditioning showed milder deficits. Analysis of response peak latency revealed subtle temporal processing abnormalities during early learning. Two months of DOX treatment initiated at four months of age prevented these learning deficits, confirming their association with tau overexpression. Conclusions: Our findings demonstrate that rTg4510 mice exhibit deficits in non-spatial temporal associative learning alongside previously reported spatial and object-recognition impairments. Trace eyeblink conditioning serves as a sensitive behavioral assay for detecting tau-related hippocampal dysfunction, and the prevention of learning deficits by DOX treatment highlights its potential utility as a translational biomarker for evaluating tau-targeted interventions. Full article

Fear memory is a critical adaptive process that enables organisms to avoid potential threats and survive in complex environments. Traditionally viewed as a neuronal phenomenon, emerging evidence has demonstrated that astrocytes play a fundamental role in fear memory acquisition, consolidation, extinction, and retrieval across the distributed neural network encompassing the amygdala, hippocampus, and prefrontal cortex. This review presents recent advances in our understanding of the molecular mechanisms by which astrocytes modulate fear memory processing within the tripartite circuit. We examine how astrocytes contribute to synaptic plasticity, neurotransmitter regulation, metabolic support, and intercellular communication during the different phases of fear memory processing. Particular emphasis is placed on the region-specific functions of astrocytes, their dynamic interactions with neurons, and their therapeutic implications for treating fear-related disorders such as post-traumatic stress disorder (PTSD) and anxiety disorders. The integration of cutting-edge technologies, including spatial transcriptomics, optogenetics, and chemogenetics, has revealed sophisticated astrocyte–neuron communication mechanisms that challenge the traditional neuron-centric view of memory processing. Full article

Fear acquisition is an essential survival mechanism for humans; however, the role and mechanisms of mindfulness training in this process remain unclear. This study employed a discriminative fear conditioning paradigm to investigate the effects and mechanisms of short-term mindfulness training, exemplified by the breath-counting task, on fear acquisition. The experiment consisted of three consecutive phases: intervention, habituation, and acquisition. During the intervention phase, each participant was assigned to one of two conditions: the breath-counting task group (experimental group) or the free reading group (control group). The results indicated that the mindfulness group exhibited significantly lower expectancy ratings for shocks to the CS− compared to the control group, while no significant difference was found in the shock ratings for CS+. Regarding skin conductance responses, although the mindfulness group showed a significantly reduced fear response to CS relative to the free reading group, there was no significant difference in overall fear acquisition effects between the two groups. The above findings indicate that breath-counting tasks enhance sensitivity to the acquisition of conditioned fear by reducing exaggerated fear responses to safety signals. The conclusions of this study further elucidate the conflicting results regarding the effects of mindfulness training on fear acquisition and provide novel perspectives for the prevention of anxiety spectrum disorders. Full article

Post-translational modifications of proteins via palmitoylation, a thioester linkage of a 16-carbon fatty acid to a cysteine residue, reversibly increases their affinity for cholesterol-rich lipid rafts in membranes, changing their function. Little is known about how altered palmitoylation affects function at the systemic level and contributes to CNS pathology. However, recent studies suggested a role for the downregulation of palmitoyl acetyltransferase (DHHC) 21 gene expression in the development of Major Depressive Disorder (MDD)-like syndrome. Here, we sought to investigate how susceptibility (sucrose preference below 65%) or resilience (sucrose preference > 65%) to stress-induced anhedonia affects DHHC gene expression in the hippocampus of C57BL/6J mice during the phase of spontaneous recovery from anhedonia. Because MDD is a recurrent disorder, it is important to understand the molecular mechanisms underlying not only the symptomatic phase of the disease but also a state of temporary remission. Indeed, molecular changes associated with the application of pharmacotherapy at the remission stage are currently not well understood. Therefore, we used a mouse model of chronic stress to address these questions. The stress protocol consisted of rat exposure, social defeat, restraint stress, and tail suspension. Mice from the stress group were not treated, received imipramine via drinking water (7 mg/kg/day), or received intraperitoneal injections of dicholine succinate (DS; 25 mg/kg/day) starting 7 days prior to stress and continuing during a 14-day stress procedure. Controls were either untreated or treated with either of the two drugs. At the 1st after-stress week, sucrose preference, forced swim, novel cage, and fear-conditioning tests were carried out; the sucrose test and 5-day Morris water maze test followed by a sacrifice of mice on post-stress day 31 for all mice were performed. Transcriptome Illumina analysis of hippocampi was carried out. Using the RT-PCR, the hippocampal gene expression of Dhhc3, Dhhc7, Dhhc8, Dhhc13, Dhhc14, and Dhhc21 was studied. We found that chronic stress lowered sucrose preference in a subgroup of mice that also exhibited prolonged floating behavior, behavioral invigoration, and impaired contextual fear conditioning, while auditory conditioning was unaltered. At the remission phase, no changes in the sucrose test were found, and the acquisition of the Morris water maze was unchanged in all groups. In anhedonic, but not resilient animals, Dhhc8 expression was lowered, and the expression of Dhhc14 was increased. Antidepressant treatment with either drug partially preserved gene expression changes and behavioral abnormalities. Our data suggest that Dhhc8 and Dhhc14 are likely to be implicated in the mechanisms of depression at the remission stage, serving as targets for preventive therapy. Full article

Background/Objectives: Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. Patients diagnosed with post-traumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with individuals exposed to early adverse experiences and women having increased vulnerability for diagnoses; however, the mechanisms of this increased vulnerability remain unknown. PTSD involves a complex network of highly interconnected brain regions, including the bed nucleus of the stria terminalis (BNST). Serotonin (5-HT) release into the BNST yields an increased expression of both fear and anxiety, specifically through 5-HT_2C receptor signaling. The present experiment addressed whether 5-HT_2C receptor signaling in the BNST is necessary for the acquisition of early-life stress (ELS)-induced enhancements in adult contextual fear learning. Methods: Rats received 0 or 15 footshocks on postnatal day 17, an established model of acute ELS (aELS) that yields enhanced adult fear learning. In adulthood, rats received bilateral infusions of a vehicle, a 5-HT_2C receptor antagonist (RS-102221), or a 5-HT_2C receptor agonist (MK-212) into the BNST 15 min prior to one-footshock contextual fear conditioning in a novel context. The next day, rats were returned to the fear-conditioning context to assess their fear memory (freezing). Results: Females demonstrated aELS-induced enhancement in contextual fear learning, while males did not. BNST infusions of RS-102221 reduced contextual fear conditioning, independent of aELS condition and sex. Infusions of MK-212 had no effect. Conclusions: Taken together, these data suggest that serotonergic signaling through 5-HT_2C receptors in the BNST contributes to contextual fear conditioning, but not aELS-induced stress-enhanced fear learning (SEFL). Full article

Fear overgeneralization is a prevalent clinical symptom of anxiety disorders. Various research studies have demonstrated that attention plays a crucial role in fear generalization. Moreover, fear is not only generalized to the stimulus, but individuals may also exhibit a certain degree of fear generalization to the context. This research investigates whether fear generalizes to stimuli and context simultaneously and the potential impact of attentional bias. The study involved two conditioned fear factors, a stimulus and context, with visual image materials combining both elements. Participants were instructed to focus on global attention in Study 1, while in Study 2, they were divided into groups based on their attention bias direction towards either stimuli or context during the fear acquisition phase. This study found that participants exhibited generalized conditioned fear to both stimuli and context, regardless of attentional bias. Additionally, participants showed a lower degree of generalization in the area to which they directed their attention during the acquisition phase. The results of this research reveal the differing expressions of fear generalization towards context and stimuli, highlighting the important role of attention in this process. Full article

This paper presents the identification of arousal and valence during visual stimuli exposure using electroencephalograms (EEGs) and functional near-infrared spectroscopy (fNIRS) signals. Specifically, various images were shown to several volunteers to evoke different emotions defined by their level of arousal and valence, such as happiness, sadness, fear, and anger. Brain activity was recorded using the Emotiv EPOC X and NIRSport2 devices separately. The recorded signals were then processed and analyzed to identify the primary brain regions activated during the trials. Next, machine learning methods were employed to classify the evoked emotions with highest accuracy values of 71.3% for EEG data with a Multi-Layer Perceptron (MLP) method and 64.0% for fNIRS data using a Bagging Trees (BAG) algorithm. This approach not only highlights the effectiveness of using EEG and fNIRS technologies but also provides insights into the complex interplay between different brain areas during emotional experiences. By leveraging these advanced acquisition techniques, this study aims to contribute to the broader field of affective neuroscience and improve the accuracy of emotion recognition systems. The findings could have significant implications for developing intelligent systems capable of more empathetic interactions with humans, enhancing applications in areas such as mental health, human–computer interactions, or adaptive learning environments, among others. Full article

Perineuronal nets (PNNs), a specialized form of extra cellular matrix (ECM), surround numerous neurons in the CNS and allow synaptic connectivity through holes in its structure. We hypothesize that PNNs serve as gatekeepers that guard and protect synaptic territory and thus may stabilize an engram circuit. We present high-resolution and 3D EM images of PNN-engulfed neurons in mice brains, showing that synapses occupy the PNN holes and that invasion of other cellular components is rare. PNN constituents in mice brains are long-lived and can be eroded faster in an enriched environment, while synaptic proteins have a high turnover rate. Preventing PNN erosion by using pharmacological inhibition of PNN-modifying proteases or matrix metalloproteases 9 (MMP9) knockout mice allowed normal fear memory acquisition but diminished long-term memory stabilization, supporting the above hypothesis. Full article

Fear over-generalization as a core symptom of anxiety disorders is manifested by fear responses even to safe stimuli that are very dissimilar to the original dangerous stimulus. The present study investigated the effects of two separate conditioned stimuli–unconditioned stimuli (CS–US) pairing procedures on fear acquisition and generalization using a perceptual discrimination fear-conditioning paradigm, with US expectancy ratings and skin conductance response (SCR) as indicators. One group accepted continuous followed by partial CS–US pairings (C–P group); the other group accepted partial followed by continuous CS–US pairings (P–C group). It was found that compared to the P–C group, the C–P group showed stronger perceptual discrimination of CS+ and CS− in the fear acquisition and showed weaker SCRs and stronger extinction of US expectancy in the generalization. These findings emphasize that CS–US pairings significantly influence fear acquisition and generalization and suggest that continuous-following partial CS–US pairings promote individual discrimination of threat and safety signals and inhibit the generalization of conditioned fear. The results of this study have implications for clinical interventions for patients experiencing negative events. Full article

Fear conditioning evokes a physiologic release of glucocorticoids that assists learning. As a cochaperone in the glucocorticoid receptor complex, FKBP51 modulates stress-induced glucocorticoid signaling and may influence conditioned fear responses. This study combines molecular and behavioral approaches to examine whether locally reducing FKBP51 expression in the ventral hippocampus is sufficient to affect fear-related behaviors. We hypothesized that reducing FKBP51 expression in the VH would increase glucocorticoid signaling to alter auditory fear conditioning. Adult male rats were injected with an adeno-associated virus (AAV) vector expressing short hairpin – RNAs (shRNA) targeting FKBP5 into the ventral hippocampus to reduce FKBP5 levels or a control AAV. Infusion of FKBP5-shRNA into the ventral hippocampus decreased auditory fear acquisition and recall. Although animals injected with FKBP5-shRNA showed less freezing during extinction recall, the difference was due to a reduced fear recall rather than improved extinction. Reducing ventral hippocampus FKBP51 did not affect exploratory behavior in either the open field test or the elevated zero maze test but did increase passive behavior in the forced swim test, suggesting that the reduction in auditory fear recall was not due to more active responses to acute stress. Furthermore, lower ventral hippocampus FKBP51 levels did not alter corticosterone release in response to restraint stress, suggesting that the reduced fear recall was not due to lower corticosterone release. Our findings suggest FKBP51 in the ventral hippocampus plays a selective role in modulating fear-learning processes and passive behavioral responses to acute stress rather than hypothalamic-pituitary-adrenal axis reactivity or exploratory responses. Full article