Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963-1·68) deaths globally, declining from 3·69 million (3·04-4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0-92·9) per 100 000 population to 16·4 (12·6-21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811-1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000-882 000) and 501 000 (373 000-648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0-21·5]), followed by norovirus (10·2% [2·4-17·0]) and Shigella spp (9·3% [5·4-15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5-48·5) for rotavirus, 24·0% (15·1-36·7) for Shigella spp, and 23·4% (13·7-34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290-49 000) and 18 800 (4650-44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. Gates Foundation.
Inbred mouse strains are essential to biomedical research, yet accumulating mutations and substrain divergence introduce phenotypic variability that can confound experimental outcomes. This study investigates behavioral differences among 13 inbred mouse substrains: eight C57BL/6 (B6) and five C57BL/10 (B10), bred in-house to control for environmental effects. Female F1 offspring underwent a standardized battery of behavioral assays-open field test (OFT), locomotor response to cocaine (LOCO), fear conditioning (FC), prepulse inhibition (PPI), and the forced swim test (FST)-chosen for their relevance to models of psychiatric and substance use disorders. Significant substrain-specific differences were observed across all behaviors. In the OFT, B6 substrains such as C57BL/6J showed higher activity than others, while B10 substrains exhibited distinct edge-zone preference patterns. Cocaine-induced locomotor stimulation varied significantly among B6 substrains but not among B10. In FC, substrain differences emerged in pre-training, contextual, and cued freezing behavior, particularly among B10 substrains. PPI testing revealed substrain-dependent variation in acoustic startle responses, with C57BL/10J displaying consistently lower startle amplitudes. In the FST, substrain-specific differences in swimming velocity and high mobility duration and frequency were found within the B6 group, while swimming distance showed substrain variation within the B10 group. These findings demonstrate substantial phenotypic variability among closely related substrains, underscoring the critical importance of substrain selection in behavioral research. By focusing on female mice (a group underrepresented in prior work), this study addresses an essential gap and provides insights for researchers designing preclinical models of psychiatric disorders. The results provide the basis for studies in reduced complexity crosses to identify causal genetic variants underlying behavioral traits.
Basketball performance emerges from the rapid integration of sensory information, motor execution, and technical skill. Neuro-athletic training (NAT) has gained attention as a sensory-driven intervention targeting visuomotor, vestibular, and proprioceptive systems to acutely enhance performance. However, evidence regarding the immediate and short-term effects of a single NAT session in youth basketball players remains limited. To investigate the acute and short-term (30 min) effects of a single-session neuro-athletic training intervention on physical and basketball-specific technical performance in male youth basketball players. Forty-two male youth basketball players (14-17 years) completed a single-group repeated-measures study. Participants performed a single-session neuro-athletic training (NAT) protocol consisting of three stations integrating visual tracking, near-far focusing, reaction-based tasks, gaze stabilization, and basketball-specific skills such as passing, dribbling, and shooting. Assessments were conducted at baseline (Pre), immediately after NAT (Immediate), and 30 min post-intervention (Post-30). Outcomes included sit-and-reach flexibility, countermovement jump (CMJ) height, 20-m sprint time, dynamic balance, and AAHPERD passing and shooting tests. Significant time effects were observed for all outcomes (all p < 0.001). Sit-and-reach performance increased from 7.69 ± 7.86 cm at Pre to 9.31 ± 7.67 cm immediately after NAT and 9.62 ± 7.79 cm at 30 min (η2 p = 0.508). CMJ height increased from 25.09 ± 5.25 to 27.66 ± 5.23 cm immediately and 28.60 ± 5.33 cm at 30 min (η2 p = 0.581), whereas 20-m sprint time decreased from 1.80 ± 0.30 to 1.62 ± 0.25 s immediately and remained lower at 1.74 ± 0.29 s at 30 min (η2 p = 0.425). Passing and shooting scores also improved markedly, increasing from 28.38 ± 3.04 to 34.62 ± 3.06 and 36.19 ± 2.99 (η2 p = 0.870), and from 16.00 ± 3.20 to 20.81 ± 3.42 and 22.81 ± 3.56 (η2 p = 0.793), respectively. A single-session neuro-athletic training intervention induced rapid and meaningful improvements in physical and basketball-specific technical performance, with several benefits retained after 30 min. These findings support NAT as an effective acute priming strategy for youth basketball performance.
Certain events that occur in early life, such as changes in nutrition, can induce structural and functional modifications in brain development, leading to behavioral programing in the offspring. These effects depend on the timing, intensity, and duration of exposure, and may contribute to chronic disorders in adulthood. Artificial non-nutritive sweeteners (NNS), such as saccharin, have recently been proposed as potential developmental disruptors. Saccharin consumption during pregnancy is discouraged, as it can cross the placenta and accumulate in the fetus. In this study, pregnant rats were administered 0.1% saccharin in drinking water throughout gestation. On postnatal day 21, offspring were assessed for behavioral outcomes using the open field and elevated plus maze tests. During sacrifice, the prefrontal cortex of the animals was collected. Gestational saccharin exposure induced sex-specific behavioral changes: offspring of saccharin-consuming mothers spent more time in the center of the arena, while only females showed increased open-arm entries. These alterations were coupled with changes in prefrontal endocannabinoid, glutamatergic, and GABAergic gene expression. Only saccharin-exposed male pups showed significant alterations in Dagla, Daglb and Gpr55 along with increased expression of glutamatergic receptors (Grin1, Grin2a, Grin2c, Gria1, Grm3). Females exhibited reduced expression of GABAergic receptor genes (Gabrg2, Gabbr2), and significant changes in the phosphorylated expression of proteins involved in the insulin pathway (IRS-1, PI3K, AKT, GSK3b). These findings suggest that developmental NNS exposure produces long-lasting behavioral outcomes in offspring, which are linked to alterations in multiple signaling pathways within the prefrontal cortex.
Dysphagia is a major consequence of Alzheimer's disease (AD) that is understudied and undertreated. Neuropathology in AD occurs early in the disease progression, but little is known about pathologies underlying functional swallowing changes; this knowledge gap is a barrier to developing effective treatment. We hypothesized that an established AD rat model (TgF344-AD) would demonstrate significant deficits in oromotor/swallowing function versus Wild Type (WT) with corresponding amyloid beta pathology in brain structures critical to swallowing. Nine male TgF344-AD and 6 Wildtype Fisher 344 rats underwent deglutition assessments and PET imaging using the radiotracer [11C]PiB to assess brain and brainstem amyloid beta (Aβ) pathology at 11 months of age-a time point corresponding to early-middle stage AD progression. A priori brain regions of interest (ROIs) included those commonly associated with Aβ pathology and more specific swallowing associated structures such as brainstem nuclei and cortical motor areas. Deglutition was assessed using a videofluoroscopic swallow study and a pasta biting task. Significantly increased levels of Aβ in the AD group were found in regions critical to swallowing motor control including the secondary motor area, thalamus, nucleus ambiguus, and hypoglossal nuclei. The AD group demonstrated significant changes in aerodigestive coordination, including delayed swallow onset, increased apnea duration, and increased frequency of aberrant post-swallow inhale pattern that was correlated with nucleus ambiguus Aβ levels. The AD group also exhibited altered oral processing including reduced bolus size and mastication rate. The TgF344-AD rat model of Alzheimer's exhibits robust changes in oral processing and respiratory-swallow coordination that parallel clinical AD dysphagia. At this early-middle stage timepoint, Aβ pathology is primarily impacting cerebral swallowing networks as well as the nucleus ambiguus and hypoglossal nuclei in the brainstem. Our finding of increased Aβ in the nucleus ambiguus warrants further study as this motor nucleus plays a role in swallowing, respiration, and vocalization-all factors that are known to be impacted by AD in the clinical population.
Early-life social experiences have a profound impact on the development of the brain and behavior. Previous work has shown that prairie voles (Microtus ochrogaster) raised in a socially limited environment (raised by a single mother and isolated after weaning) engaged in more social behaviors compared to those raised in a socially enriched environment (raised biparentally and group-housed after weaning). Furthermore, intranasal oxytocin has been therapeutically used in children, yet little is known about how this might affect brain development. Oxytocin is a crucial neuropeptide involved in social behavior and cognition, and variation in parental care and early social experiences has the potential to alter oxytocin receptors (OTR) throughout the brain. However, few studies have asked how different social experiences interact to alter brain phenotype. In this study, male prairie voles were raised in either a socially limited condition (raised by a single mother and isolated after weaning) or raised in a socially enriched condition (raised biparentally and group housed after weaning). Subjects in each condition were also administered either intranasal oxytocin or saline (PND 21-42). Finally, brains were collected, and we used autoradiography to quantify OTR throughout the brain of these animals. It showed that much of the forebrain did not show differences in OTR density as a result of either manipulation, reinforcing the idea that OTR phenotype is generally resistant to external forces. However, we found two important exceptions to this theme in the prefrontal cortex and the lateral septum - two areas of the brain that are critical to social behavior in general and prairie vole pair bonding in particular. Specifically, socially limited animals had significantly more OTR in the prefrontal cortex compared to socially enriched animals, and subjects administered intranasal oxytocin during adolescent development expressed more OTR in the lateral septum compared those treated with saline. Although the impacts of external sources on OTR density appear to be restricted to only a few locations in the brain, these brain regions are central to social functioning, indicating limited but potentially significant impacts on social behaviors are plausible.
Physical inactivity among children and adolescents has reached critical levels worldwide, with approximately 81% of school-aged youth failing to meet the World Health Organization recommendation of at least 60 min of moderate-to-vigorous physical activity per day. At the same time, screen-based sedentary behaviors have increased substantially, raising concerns about their combined impact on brain development, cognitive processes, and behavioral regulation. Although extensive research exists, evidence regarding dose-response relationships, neurobiological mechanisms, and the moderating role of screen-related behaviors remains fragmented. This scoping review aimed to systematically map the evidence linking physical activity and sedentary behavior with cognitive outcomes in children and adolescents, examine dose-response patterns, synthesize underlying neurobiological mechanisms (including brain-derived neurotrophic factor and neuroplasticity), and evaluate the moderating influence of screen time and smartphone-related behaviors. The review followed PRISMA-ScR guidelines and the Joanna Briggs Institute methodology. Six electronic databases (PubMed/MEDLINE, Scopus, Web of Science, SPORTDiscus, PsycINFO, and CINAHL) were searched for studies published between January 2000 and March 2026. Eligibility criteria were defined using the Population-Concept-Context framework. Two independent reviewers conducted screening, achieving strong inter-rater reliability (κ = 0.84). Of 2,843 records identified, 60 studies met inclusion criteria across four thematic domains: physical activity and cognitive outcomes, dose-response parameters, neurobiological mechanisms, and screen-based sedentary behavior including nomophobia. Chronic physical activity, particularly in school-based and clinical ADHD settings, was consistently associated with executive function improvements across included systematic reviews and trials. Screen time exceeding 4 h per day was associated with anxiety, depressive symptoms, and attentional deficits in observational data. Evidence on exercise-induced BDNF upregulation, contingent on structured exposure (≥3 sessions/week, ≥12 weeks), is restricted to five pediatric RCTs and warrants cautious interpretation. This scoping review maps consistent associations between physical activity and improved cognitive function in youth, mediated through neurobiological pathways that vary in strength across study designs and populations. Excessive screen exposure is associated with cognitive risk in observational data. Integrated public health frameworks addressing physical activity, screen time, and sleep represent a priority direction for future longitudinal research and policy development.
Perinatal mental health is a major public health concern. Epidemiological studies indicate that approximately 10-20% of women in the postpartum period experience clinically significant depressive or obsessive-compulsive symptoms. Many postpartum symptoms involve heightened vigilance and behaviors aimed at protecting the infant from possible harm, suggesting the presence of offspring-centered defensive processes. One offspring-centered defensive behavior described in wild rats is entrance-sealing, in which lactating females plug the entrance of their burrow to limit access by potential intruders. Although laboratory mice rarely exhibit such behavior spontaneously, similar bedding-plugging behavior has been occasionally observed, suggesting that mice retain the capacity for this response. However, no method has existed for reliably quantifying such behavior under controlled laboratory conditions. To address this gap, we developed the Tube-Plugging Test (TPT), an assay that measures bedding accumulated at tube-like openings attached to the home cage and enables repeated, non-invasive quantification of plugging behavior. Using this approach, we found that tube plugging occurred rarely in males, intermittently in virgin females, and most robustly in postpartum females. Notably, plugging behavior exhibited substantial inter-individual variability, but was more temporally stable across days in postpartum females than in virgin females. In postpartum females, exposure to a male intruder altered plugging behavior at the tube through which the intruder was introduced, suggesting that plugging is modulated by direct social context. Together, these findings establish the TPT as a simple and reproducible method for quantifying plugging behavior and identify tube plugging as a measurable component of offspring-centered defensive behavior.
In the quest to investigate the internal cognitive mechanisms underlying consumer behavior, often metaphorically termed the "black box," studies indicate that purchasing decisions are significantly influenced by implicit cognitive processes. Conventional data collection methods that appeal to the conscious level may mislead marketing strategies. This motivates the rapid increase of research in two fields: psychology and neuroscience. This interdisciplinary research was focused on the cultural unconscious. Similar to the archetypes (the building blocks of the collective unconscious), cultural codes (the building blocks of the cultural unconscious) play a crucial role in shaping purchasing decisions. Based on this, the research question is "What is the cultural code of the selected product in the social unconscious of the target population?" This research comprises two consecutive sub-studies: in-depth interviews (Study 1), and an fMRI task (Study 2). A heavy-duty vehicle (truck) was chosen as the product, and professional truck drivers (n = 22 for Study 1 and n = 34 for Study 2) from Nortwest Anatolia, in Türkiye, were selected to represent the target population. In Study 1, the unconscious cultural code associated with the truck was discovered as "migration" through in-depth interviews utilizing psychoanalytic and transactional approaches. In Study 2, an fMRI experiment was developed to test whether the "truck + migration" image would elicit brain activation patterns similar to those associated with unconscious relational encoding and retrieval, reported in the literature (fusiform gyrus, middle temporal gyrus, parahippocampus / hippocampus, precuneus, angular gyrus, anterior cingulate), and significantly different from those elicited by control images. Detecting these specific activations would provide neuroscientific support for the hypothesis that the concepts of truck and migration are relationally encoded in participants' cultural unconscious, thereby validating the qualitative findings by in-depth interviews. Identifying a product's unconscious cultural code enables a more precise design of the marketing mix. By using these interdisciplinary qualitative and quantitative methods sequentially, an innovative and original method was developed, yielding both theoretical contributions in cultural code discovery and consumer neuroscience, as well as practical implications, particularly in marketing.
We propose that the excitability margin (ΔV margin ), defined as the difference between spike threshold and resting membrane potential, may function as a quantitative gating variable linking chronic stress, inflammatory load, and transient increases in excitability associated with reactivation to emotionally polarized replay or other maladaptive forms of circuit reactivation. Based on a conceptually guided integration of published electrophysiological data, we modeled how chronic restraint stress, a conservatively parameterized stress-associated inflammatory component, and a transient state of increased engram reactivity may jointly reduce the excitability reserve of ventral CA1 (vCA1) pyramidal neurons. In the main scenario, the model-derived effective margin decreased from 18.4 mV to approximately 6.0 mV, corresponding to a 67.5% reduction. Additional illustrative pro-excitatory scenarios further reduced the margin to approximately 4.3 mV, 3.7 mV, or 1.7 mV. These values fall within the range of physiologically reported amplitudes of transient depolarizing events, including local NMDA spikes, sharp wave-associated depolarizations, intracellular ripples, and larger subthreshold burst-related events. This suggests that in circuits where analogous transient depolarizing events occur, narrowing of ΔV margin may increase the likelihood that otherwise subthreshold network activity contributes to threshold crossing and maladaptive reactivation. We therefore hypothesize that progressive narrowing of ΔV margin may act as a gating mechanism for preferential reactivation of vulnerable neuronal ensembles, increasing the probability of repetitive, emotionally polarized replay or other maladaptive forms of circuit reactivation and secondary circuit destabilization. This framework may provide a unifying excitability-based mechanistic hypothesis and a hypothesis-generating transdiagnostic framework relevant to schizophrenia-, depression-, and trauma-related phenotypes, while remaining potentially informative for other conditions characterized by excitability instability. The model generates clear, falsifiable predictions: interventions that widen ΔV margin or reduce trigger efficacy should attenuate hyperreactivity in the vCA1/vHipp system analyzed here and limit secondary markers of network dysregulation, while also providing a transferable framework for testing analogous low-margin dynamics in other phenotype-relevant circuit nodes.
The purpose of the present paper is not to validate the metaphysical claims of yogic traditions, but to examine whether their phenomenological descriptions correspond to measurable physiological processes. The proposal advanced here is explicitly theoretical: a hypothesis-generating model informed by preliminary retrospective clinical observations, not a claim of established proof. All interpretations of iconographic material are advanced as phenomenological correspondences - possible mappings onto identifiable neurophysiological states - rather than assertions of historical or archaeological fact. Kundalini has been described in yogic literature as a transformative psychophysiological process, with systematic iconographic representations that date back across millennia. Its physiological basis remains undefined within contemporary neuroscience. This article proposes that the phenomenological descriptions embedded in classical Indian iconography may correspond in structure and sequence to identifiable neurophysiological states of autonomic integration. This article proposes a neurophysiological theoretical framework for interpreting kundalini phenomena, drawing on preliminary, retrospective clinical observations, published neuroscience, and cross-tradition phenomenological analysis. A retrospective analysis of a 14-year single-practitioner observational dataset comprising 404 consecutive patients treated for autonomic dysregulation, sleep disturbance, and attentional dysfunction using non-invasive, non-pharmacological interventions. No randomisation or control arm was employed. The dataset is presented as exploratory and hypothesis-generating clinical evidence rather than experimental proof. Observed patterns-including improvements in heart rate variability (HRV), cortisol diurnal rhythm restoration, and attentional stability-are associated with a progressive nervous system integration trajectory consistent with the classical bottom-up kundalini model. The neural dispersion index (NDI), proposed in this study as an exploratory heuristic synthesis metric requiring independent validation, is used to track these changes across a seven-domain profile. The natural clinical progression follows a four-stage sequence: fragmentation (NDI > 60) → dormant baseline (NDI 40-60) → progressive integration (NDI 25-40) → threshold coherence (NDI < 25). Preliminary observations support a testable neurophysiological model of kundalini as a process of progressive autonomic and cortical integration. The model generates four specific falsifiable predictions. Formal prospective investigation is required before any clinical conclusions can be drawn.
Early identification of childhood behavioural markers using wearable sensing is important for timely intervention in developmental and sleep-related disorders. Wrist-worn accelerometer data provide objective measures of behavioural regulation by capturing actigraphy-derived states such as Sleep, Wake, and Transitional periods. However, existing deep learning methods for behavioural state detection often face challenges related to redundant features, sensitivity to sensor noise, limited robustness in long-term wearable deployment, and high energy consumption. This study proposes a Quantum Variational Feature Selection-Spiking Graph Transformer Network (QVFS-SGTN), a hybrid quantum-neuromorphic framework for robust and energy-efficient behavioural state classification. The prediction task was defined as a three-class classification problem involving Sleep, Wake, and Transitional behavioural states from high-frequency wrist-worn accelerometer data. The proposed model integrates a parameterized quantum circuit-based feature selector to identify non-linear and entangled sensor correlations. Selected features are then processed by a spiking graph transformer network, which models temporal dependencies through event-driven self-attention and neuromorphic neuron dynamics. Experiments were conducted using the Child Mind Institute wearable dataset, with additional cross-dataset validation performed on the external Multi-Ethnic Study of Atherosclerosis sleep dataset. The proposed QVFS-SGTN framework achieved state-of-the-art performance on the Child Mind Institute wearable dataset, with an accuracy of 0.968, an F1-score of 0.968, and an AUC of 0.991. Robustness evaluation demonstrated stable performance under significant Gaussian noise, maintaining accuracy above 92%. Energy analysis showed a 40-55% reduction in computational cost compared with conventional deep learning models. In cross-dataset evaluation using the MESA sleep dataset, the model achieved an accuracy of 0.931 without fine-tuning, indicating strong generalization capability. The findings demonstrate that combining quantum-enhanced feature selection with spiking graph-based temporal modelling can improve the robustness, accuracy, and energy efficiency of wearable behavioural state detection. The QVFS-SGTN framework effectively addresses key limitations of existing deep learning approaches, including feature redundancy, sensor noise sensitivity, and computational cost. These results support the potential of the proposed hybrid quantum-neuromorphic model for scalable, long-term, real-world paediatric behavioural monitoring.
Brain-derived neurotrophic factor (BDNF) is a key player in the molecular mechanisms underlying learning and memory in mammals. Recent studies have shown that mutant fish lacking BDNF exhibit widespread deficits in learning tasks. Moreover, natural variation in brain BDNF gene expression predicts individual differences in learning ability in fish. These findings suggest that the role of BDNF in cognition may be widespread among vertebrates. Following this hypothesis, we used a bdnf knockout zebrafish model to investigate whether BDNF is involved in recognition memory in fish. Zebrafish larvae were tested in a novel object recognition test, where their response to a previously encountered stimulus and a novel one was recorded. Overall, zebrafish did not demonstrate a group-level preference for either stimulus. However, individuals appeared to show variation in their responses to the novel stimulus (either approaching or avoiding it). When accounting for the individual variation, the strength of recognition memory performance was lower in zebrafish lacking bdnf compared with control zebrafish, although this effect was influenced by the type of stimulus used. Moreover, the absence of BDNF resulted in less variability in the behavioral response towards the novel stimulus, supporting the role of this protein in shaping individual differences in behavior. Our findings suggest that BDNF may be involved in recognition test performance and the underlying behavior, although the nature of this involvement and the contribution of memory processes remain unclear.
Women are especially vulnerable to stress-related disorders such as posttraumatic stress disorder (PTSD), yet most preclinical studies have focused on males. Rodents often exhibit sexually-dimorphic coping strategies in fear behaviors, thus complicating neurobiological interpretations. To facilitate comparisons, an operant conditioned suppression paradigm was implemented where the measure of fear is not dependent on the coping strategy. The effect of single prolonged stress (SPS) on fear behavior was assessed. Since stress has been linked to excitatory phenotypes, mRNA expression of vesicular glutamate transporter 1 (VGLUT1) and glutamate decarboxylase (GAD1) was measured to assess excitation and inhibition-related markers in the ventral hippocampus (vHip), a stress-sensitive brain region. Activity-regulated cytoskeleton associated protein (Arc/Arg3.1) was used to identify neurons activated during fear extinction. The goal of this study was to determine whether SPS produces sex differences in conditioned-suppression fear behavior and to identify accompanying molecular changes in the vHip. Thirty-two adult male and female Long Evans rats (n = 16/sex) were trained to lever press for sucrose on variable-interval (VI) schedules. After stable responding, a subset (8/sex) underwent single prolonged stress (SPS). All rats received fear conditioning with five presentations of a conditioned stimulus (CS)-shock pairing. Extinction sessions included baseline VI-60 responding followed by CS presentations. Fear was defined as the suppression of lever pressing during CS. Tissue containing the vHip was collected following the last session for RNA in situ hybridization (RNA-ISH) to examine mRNA expression of molecular markers of excitation/inhibition (VGLUT1, GAD1) and neuronal activation (Arc). SPS impaired extinction in males on day 1 but had no effect in females. On day 2, males showed greater fear than females regardless of SPS. No significant effects were observed on day 3 or the recall session. No significant effects of sex or stress were observed on vHip mRNA expression of VGLUT1, GAD1, or Arc under the experimental conditions. These findings demonstrate sex-specific effects of SPS on fear extinction measured by conditioned suppression. Future studies should explore earlier time points, additional regions (e.g., amygdala and medial prefrontal cortex) hormonal modulation, and interventions that may mitigate SPS effects in males and females.
Trait anxiety refers to the individual variability in the predisposition to respond anxiously to stimuli. Anxiety has been shown to affect several physiological processes, including fine motor tasks, both in humans and in rodents. Therefore, trait anxiety may be a confounder factor in behavioral studies assessing motor functions in preclinical animal models. Among the tools employed to investigate motor functions in rodents, CatWalk XT is one of the most used. CatWalk XT is a computer-assisted apparatus that allows rapid and objective quantification of both static and dynamic gait parameters in rodents. The test consists of a training period in which the mouse learns to cross a platform and a test day in which the mouse footprints are recorded and analyzed. Here, we investigated whether trait anxiety, assessed with the Elevated Plus Maze (EPM) test, influences mice performance on CatWalk XT. The results showed a correlation between anxiety levels as measured by the EPM and CatWalk test, with trait anxiety affecting the CatWalk learning and gait parameters. Indeed, mice with higher degrees of anxiety displayed a higher number of noncompliant runs during the training, ultimately protracting the time required by the experimenter to perform the CatWalk test. In addition, mice displaying fewer total entries in the EPM exhibited increased print lengths when assessed with the CatWalk system. In conclusion, our findings indicate that individual differences in trait anxiety must be considered when testing mice with the CatWalk XT system. The use of specific anxiety tests before CatWalk testing may be useful to exclude those mice showing the highest levels of anxiety. This strategy would optimize researcher's time, limit animals' stress, and avoid errors in the results interpretation.
Rodent studies of the taste system commonly employ two methods of taste administration (MOA): active licking from spouts or intra-oral cannula (IOC) deliveries. While bottle drinking preserves natural consumption behavior, IOC administration, where animals receive liquids passively into their oral cavity, provides precise temporal control of stimulus delivery but limits the reliability of measuring voluntary intake and hedonic response. To overcome these limitations, a third method, nose-poke for IOC delivery (NP-IOC), was introduced. In NP-IOC, each taste is delivered through the IOC following an active nose poke, thus combining voluntary decision-making with temporal precision. Whether NP-IOC preserves natural taste-guided behavior, however, remains unknown. Here, we examined how NP-IOC affects taste neophobia (the reluctance to consume novel tastes) and conditioned taste aversion (CTA, avoidance of a taste paired with malaise). Rats received water either via standard bottle licking (control) or through the NP-IOC system. Following habituation, animals were tested for neophobia using low-neophobic (LN) sucrose or high-neophobic (HN) saccharin solutions, followed by CTA training via lithium chloride injection. Our results showed sexual differences in neophobia using NP-IOC: males preserved the expected difference between LN and HN tastes, whereas females showed attenuated neophobia, eliminating the typical HN avoidance observed with bottle administration. Nevertheless, CTA learning remained robust across sexes and MOAs. Deeper analysis of this seemingly similar learned aversion, however, revealed again sex differences: while male rats showed strong CTA regardless of pre-CTA consumption, females maintained a correlation between pre and post-CTA consumption under both MOAs, suggesting sex-specific taste learning patterns. These findings support the use of NP-IOC in taste research that requires both precise stimulus control and voluntary behavior, while also underscoring the necessity of exploring divergent behavioral strategies and the associated brain circuits in males and females.
Once recognized only in humans, variance in the cognitive phenotype is now acknowledged in a range of vertebrate species. However, our understanding of its underlying causes is still incomplete. Brain-derived neurotrophic factor (BDNF) is an essential protein for brain functioning and plays a key role in cognitive processes such as learning and memory, including interindividual variation. Environmental factors influence BDNF abundance in the brain, and so do genetic polymorphisms in humans and mice. Using the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel of near-isogenic medaka lines, which captures a wide range of natural genetic variation in this species, we investigated the potential quantitative genetic variation in bdnf gene expression in the brain. Our findings show significant variation in bdnf mRNA expression levels across MIKK lines, with a two-fold difference between the lines exhibiting lower and higher expression. Seasonal variation was also observed, with higher average bdnf levels in summer. However, a tentative analysis suggested that this average effect was not consistent across the lines, with some lines even showing significantly greater expression in winter. Similarly, across the entire sample, males and females did not differ in bdnf expression overall, although some lines displayed sex differences greater than expected by chance. These results suggest that quantitative genetic differences, in concert with environmental influences, contribute to bdnf expression variability.
Non-human models, including fish, are increasingly important for investigating how pharmacological agents such as hallucinogens influence behavior, physiology, and cellular processes. These models help to reveal underlying mechanisms and to support assessments of toxicological impact, efficacy, and safety. In this study, we used isogenic lineages of the amphibious mangrove rivulus (Kryptolebias marmoratus), an emerging model fish known for high activity and socially dynamic interactions. This species often display aggression towards conspecifics making it well-suited to study behavioral effects of low doses of the psychoactive compound, psilocybin. We determined whether psilocybin could induce calming effects and reduce social aggression and activity. We socially stimulated fish using pairs of size-matched fish from different isogenic lineages and compared baseline social behavior following a waterborne dose of psilocybin. Waterborne psilocybin treatment resulted in a significant decrease in activity levels and in the frequency of swimming bursts (an aggressive behavior) towards a conspecific fish from a different lineage, with modest alterations on other behaviors. Our results also revealed considerable intraspecific variation in the behavioral response of these homozygous fish, suggesting the effects of psilocybin were largely independent of genotype. This study demonstrates that psilocybin reduces aggression and activity in an emerging fish model, adding to the evidence supporting its potential as a therapeutic agent for future clinical translation.
Cannabinoids have emerged as potential modulators of pathological processes in Alzheimer's disease (AD), including neuroinflammation, synaptic dysfunction, and protein aggregation. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main phytocannabinoids from Cannabis sativa, interact with the endocannabinoid system and may influence neuronal and glial signaling pathways relevant to AD pathology. This mini review summarizes evidence from transgenic animal models and clinical studies evaluating CBD, THC, and their combination in AD. Preclinical studies show that CBD and THC reduce β-amyloid accumulation, attenuate tau phosphorylation, and regulate neuroinflammatory responses, often associated with improvements in learning and memory. Cognitive outcomes appear to depend on cannabinoid composition, with CBD or THC administered individually showing more consistent effects, while combined CBD + THC effects appear dose- and ratio-dependent. Clinical evidence in AD patients remains limited and primarily reports improvements in neuropsychiatric symptoms, such as reductions in agitation, nighttime activity, and behavioral disturbances, whereas cognitive improvements are modest. Cannabinoid-based treatments are generally well tolerated, with mild sedation, somnolence, or disorientation as the most reported adverse effects. Overall, current data support the biological plausibility of cannabinoids as modulators of neuroinflammatory and synaptic processes in AD. However, heterogeneity in formulations, dosing, and study design limits firm conclusions. Future research should focus on dose optimization, biomarker-guided clinical trials, and long-term safety assessments to better define their therapeutic potential in AD.
The ability to understand complex sentences, such as passives, improves during middle childhood. However, it remains unknown when children transition from a "wait-and-listen" strategy to incremental, word-by-word revision of interpretive hypotheses, and whether behavioral accuracy reflects mature online processing. Using eye-tracking in a sentence-picture matching task, we examined how Russian-speaking children aged 6-7 years (n = 16), 8-10 years (n = 16), and adults (n = 35) process four sentence types (active/passive, direct/reversed word order). Semantic cues were minimized, forcing reliance on morphosyntactic markers. Linear mixed models treated age as a continuous variable to capture fine-grained trajectories. Accuracy improved sharply between ages 7 and 8, with 8-10-year-olds performing at adult levels. However, oculomotor patterns revealed a clear dissociation: at the critical second word in passive direct sentences-where the participle signals thematic role revision-adults and 8-10-year-olds showed a distinct signature (decreased fixation time, increased gaze returns), indicating rapid incremental revision. This signature was absent in 6-7-year-olds, who delayed engagement until the third word. Linear mixed models confirmed that age-related increases in fixation duration were specifically tied to this revision point, extending previous ERP findings that localized revision effects only to the third word. Adult-like behavioral accuracy by age 8-10 masks continued immaturity of incremental revision mechanisms. Eye-tracking captures this dissociation, positioning it as a sensitive marker of syntactic development and revealing that the ability to use morphosyntactic cues for real-time revision continues to develop beyond middle childhood.