Search

• A high-fat diet impairs learning and memory in male mice and increases anxiety-like behavior across sexes and ages. • A high-fat diet exacerbates systemic inflammation across age and sex in mice and induces microglia in aged male mice. • Hypothalamic proteome reveals metabolic stress induced by a high-fat diet in aged male mice. Aging and age-related diseases are associated with cellular stress, metabolic imbalance, oxidative stress, and neuroinflammation, accompanied by cognitive impairment. Lifestyle factors such as diet, sleep fragmentation, and stress can potentiate damaging cellular cascades and lead to an acceleration of brain aging and cognitive impairment. High-fat diet (HFD) has been associated with obesity, metabolic disorders like diabetes, and cardiovascular disease. HFD also induces neuroinflammation, impairs learning and memory, and may increase anxiety-like behavior. Effects of a HFD may also vary between sexes. The interaction between Age- and Sex- and Diet-related changes in neuroinflammation and cognitive function is an important and poorly understood area of research. This study was designed to examine the effects of HFD on neuroinflammation, behavior, and neurodegeneration in mice in the context of aging or sex differences. In a series of studies, young (2–3 months) or old (12–13 months) C57BL/6J male mice or young male and female C57Bl/6J mice were fed either a standard diet (SD) or a HFD for 5–6 months. Behavior was assessed in Activity Chamber, Y-maze, Novel Place Recognition, Novel Object Recognition, Elevated Plus Maze, Open Field, Morris Water Maze, and Fear Conditioning. Post-mortem analyses assessed a panel of inflammatory markers in the plasma and hippocampus. Additionally, proteomic analysis of the hypothalamus, neurodegeneration, neuroinflammation in the locus coeruleus, and neuroinflammation in the hippocampus were assessed in a subset of young and aged male mice. We show that HFD increased body weight and decreased locomotor activity across groups compared to control mice fed a SD. HFD altered anxiety-related exploratory behavior. HFD impaired spatial learning and recall in young male mice and impaired recall in cued fear conditioning in young and aged male mice, with no effects on spatial learning or fear conditioning in young female mice. Effects of Age and Sex were observed on neuroinflammatory cytokines, with only limited effects of HFD. HFD had a more significant impact on systemic inflammation in plasma across age and sex. Aged male mice had induction of microglial immunoreactivity in both the locus coeruleus (LC) and hippocampus an effect that HFD exacerbated in the hippocampal CA1 region. Proteomic analysis of the hypothalamus revealed changes in pathways related to metabolism and neurodegeneration with both aging and HFD in male mice. Our findings suggest that HFD induces widespread systemic inflammation and limited neuroinflammation. In addition, HFD alters exploratory behavior in male and female mice, and impairs learning and memory in male mice. These results provide valuable insight into the impact of diet on cognition and aging pathophysiology. [ABSTRACT FROM AUTHOR]

Leading philosophical models of curiosity represent it as a desiderative attitude whose content is a question, and which is satisfied by knowledge of the answer to that question. I argue that these models do not capture the distinctive character of a form of curiosity that I call 'erotic curiosity'. Erotic curiosity addresses itself not to a question but to an object whose significance for the inquirer is affective as well as epistemic. This form of curiosity is best understood by analogy to erotic love as theorized by Plato in the Symposium. [ABSTRACT FROM AUTHOR]

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the "metabolic syndrome". We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conducted in the plasma and frontal cortex. We also investigated the reversal effect of postpartum carbetocin (Cbt) on these signatures, along with its impact on deficits in cognitive, social, and exploratory behavior. We found that PRS induced long-lasting changes in biomarkers of secondary bile acid metabolism in the plasma and glutathione metabolism in the frontal cortex. Cbt treatment demonstrated disease-dependent effects by reversing the metabolite alterations. The metabolomic signatures of PRS were associated with long-term cognitive and emotional alterations alongside endocrinological disturbances. Our findings represent the first evidence of how early life stress may alter the metabolomic profile in aged individuals, thereby increasing vulnerability to CNS disorders. This raises the intriguing prospect that the pharmacological activation of oxytocin receptors soon after delivery through the mother may rectify these alterations. [ABSTRACT FROM AUTHOR]

Environmental enrichment has the potential to improve the welfare and post‐release survival of hatchery fish stocked for conservation purposes. However, the effectiveness of environmental enrichment is partly dependent on the fish species, life stage, and specific enrichment structure used. To enhance the effectiveness of environmental enrichment, it is crucial to focus on characteristic differences in enrichment structures, such as type and level. This study investigated how differences in enrichment type and level affected physiological and behavioral aspects of the welfare of pre‐release juvenile rock bream Oplegnathus fasciatus by evaluating growth performance, basal and stressed cortisol levels, antioxidant enzyme activities, and exploratory behaviors regarding anxiety and flexibility. Fish were reared for 4 weeks in different enrichment treatments: barren, low‐level cover structure, high‐level cover structure, low‐level interference structure (LI), and high‐level interference structure (HI). The results revealed that fish reared with the LI treatment showed less anxiety and greater flexibility with respect to exploratory behaviors, without oxidative damage being detected. Despite exhibiting less anxiety as well, fish reared in the HI treatment had oxidative damage, indicated by lower superoxide dismutase activity, compared to those in the barren treatment. In addition, none of these enrichment structures enhanced growth performance or mitigate chronic and acute stress responses. Overall, the low‐level interference structure may be more favorable in promoting the behavioral welfare of the fish. Application of this type and level of enrichment may increase the survival of the hatchery fish after release, which is critical to stocking success. [ABSTRACT FROM AUTHOR]

Background: Research reproducibility is a common problem in preclinical behavioral science. Mice are an important animal model for studying human behavioral disorders. Experimenters, processing methods, and rearing environments are the main causes of data variability in behavioral neuroscience. It is likely that mice adapt their behavior according to the environment outside the breeding cage. We speculated that mice housed on elevated shelves and mice housed on low shelves might have differently altered anxiety‐like behavior toward heights. Purpose: The purpose of this study was to investigate potential behavioral changes in mice raised at different heights for 3 weeks. Changes in behavior were examined using various experimental tests. Results: Mice housed on elevated shelves showed reduced anxiety‐like behavior in a light/dark traffic test compared with mice housed on low shelves. There were no significant differences between the two groups in terms of activity, exploratory behavior, muscle strength, or depression‐like behavior. Conclusions: Our results indicate that different cage heights and corresponding light exposure may alter the anxiety‐like behavior of mice in response to brightness. Researchers need to carefully control the cage height and light intensity experienced by the mice to produce reproducible test results. [ABSTRACT FROM AUTHOR]

This study was conducted to elucidate the possible protective efficiency of Echinacea purpurea hydroethanolic extract (EchEE) against bifenthrin (BIF)-induced neuro-chemical and behavioral changes in rats. Total phenolics content, reducing power and radical scavenging activity of EchEE were estimated. Four groups of adult male albino rats were used (10 rats each) as follows: 1) Control healthy rats ingested with placebo, 2) Healthy rats orally received EchEE (465 mg/kg/day), 3) Rats intoxicated with BIF (7mg/kg/day) dissolved in olive oil, and 4) Rats co-treated with EchEE (465 mg/kg/day) besides to BIF (7mg/kg/day) intoxication. After 30 days, some neuro-chemical and behavioral tests were assessed. The behavioral tests revealed that rats received BIF exhibited exploratory behavior and spatial learning impairments, memory and locomotion dysfunction, and enhanced anxiety level. Biochemical findings revealed that BIF induced-oxidative stress in the cortex and hippocampus; this was appeared from the significant rise in malondialdehyde (MDA) and nitric oxide (NO) levels, coupled with decreased catalase (CAT), superoxide dismutase (SOD), paraoxonase-1 (PON-1) activities, and reduced glutathione (GSH) level in both brain areas. Also, BIF induced a significant increase caspas-3, tumor necrosis factor alpha (TNF), and interleukin-1beta (IL-1ß) in both areas; dopamine and serotonin levels, and ACh-ase activity were markedly decreased in both areas. Interestingly, treatment of rats with EchEE in combination with BIF resulted in a significant decrease in oxidative stress damage, and modulation of the apoptotic and pro-inflammatory markers. Also, EchEE markedly improved behavioral activities and neurotransmitters level that were impaired by BIF. In conclusion, the present study clearly indicated that EchEE can attenuate brain dysfunction induced by pesticides exposure through preventing the oxidative stress. This may be attributed to its high antioxidant component. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that there was no significant difference in the number and duration of seizures between treated and untreated animals. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective in preventing neuron loss in the hippocampal CA3 field compared to combination treatment. The treatment alleviated the impairments in activity level, exploratory behavior, and anxiety but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, either alone or in combination, may be clinically useful in preventing the development of histopathological and behavioral abnormalities associated with epilepsy. [ABSTRACT FROM AUTHOR]

As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia's important involvement in the pathology and progression of Alzheimer's disease (AD), understanding whether systemically administered drugs intended for other affections could impact microglia function, already impacted by the presence of beta-amyloid, is important. The aim of this study was to evaluate morphological changes of microglia, using in vivo 2-photon laser scanning microscopy, in a murine model of AD under systemic administration of sodium or calcium ion channel blockers in order to establish potential effects that these drugs might have on microglia under neuro-inflammatory conditions. A total of 30 mice (age 14–16 weeks, weight 20–25 g) were used, with 25 APP randomly divided into three groups. The remaining animals were CX3CR1GFP/GFP male mice (n = 5) used as WT controls. After baseline behavior testing, all animals received daily intraperitoneal injections for 30 days according to the assigned group [WT (n = 5), Control (n = 5), Carbamazepine (n = 10), and Verapamil (n = 10)]. The results showed that the Verapamil treatment improved short-term memory and enhanced exploratory behavior in APP mice. The Carbamazepine treatment also improved short-term memory but did not elicit significant changes in anxiety-related behavior. Both Verapamil and Carbamazepine reduced the surveillance speed of microglia processes and changed microglia morphology in the cortex compared to the Control group. Due to their complex molecular machinery, microglia are potentially affected by drugs that do not target them specifically, and, as such, investigating these interactions could prove beneficial in our management of neurodegenerative pathologies. [ABSTRACT FROM AUTHOR]

Curiosity has been seen as an important driver of individual innovation. However, empirical evidence regarding the relationship between curiosity and innovation is equivocal. We draw on the situational strength perspective to develop and test a contingency model that focuses on the contextual boundary conditions of this relationship among Chinese employees. In a controlled experiment with 191 part‐time MBA students, in which curiosity was examined as a state, we found that (1) the main effect of curiosity on innovative behavioral intention was insignificant; (2) authoritarian leadership and job autonomy moderated the association of curiosity with innovative behavioral intention, such that this association was positively significant under circumstances of low authoritarian leadership or high job autonomy but not under circumstances of high authoritarian leadership or low job autonomy; and (3) job autonomy functioned as a mediator for the moderating effect of authoritarian leadership. These findings were constructively replicated in a field study of 206 subordinate–supervisor dyads in which curiosity was examined as a trait and innovative behavior was rated by supervisors. Theoretical and practical implications of our findings and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Adhesion molecules play major roles in cell proliferation, migration, survival, neurite outgrowth and synapse formation during nervous system development and in adulthood. The neural cell adhesion molecule L1 contributes to these functions during development and in synapse formation and synaptic plasticity after trauma in adulthood. Mutations of L1 in humans result in L1 syndrome, which is associated with mild-to-severe brain malformations and mental disabilities. Furthermore, mutations in the extracellular domain were shown to cause a severe phenotype more often than mutations in the intracellular domain. To explore the outcome of a mutation in the extracellular domain, we generated mice with disruption of the dibasic sequences RK and KR that localize to position 858RKHSKR863 in the third fibronectin type III domain of murine L1. These mice exhibit alterations in exploratory behavior and enhanced marble burying activity. Mutant mice display higher numbers of caspase 3-positive neurons, a reduced number of principle neurons in the hippocampus, and an enhanced number of glial cells. Experiments suggest that disruption of the dibasic sequence in L1 results in subtle impairments in brain structure and functions leading to obsessive-like behavior in males and reduced anxiety in females. [ABSTRACT FROM AUTHOR]

DAT-HET rats with their underlying hyperdopaminergia are a promising model for the investigation of neuropsychiatric diseases, which are based on impaired dopamine neurotransmission, including alcoholism. The aim of the work was to evaluate the effect of free alcoholization on drinking, locomotor, exploratory behavior, anxiety, and Tyrosine hydroxylase (TH) levels in rats with impaired functioning of the DA system (DAT-HET). The study was carried out on adult male rats of the DAT-HET (n = 15) and Wistar (n = 13), which were divided into 4 groups: "DAT-HET ethanol" (n = 10) and "Wistar ethanol" (n = 9), who were in the mode of free alcoholization for 112 days of the experiment. The DAT-HET water (n = 5) and Wistar water (n = 4) groups did not have access to an ethanol solution and did not participate in behavioral tests. Ethanol preference and consumption was assessed in the "Two-bottle choice test". The amount of ethanol consumed in the cells was recorded weekly. Behavior was assessed using the Open Field and Elevated Plus Maze tests. After alcoholization, to assess the level of TH, an immunohistochemical (IHC). It was found that during free alcoholization, DAT-HET rats do not form preferences for ethanol. Under the low ethanol consumption, the initial hyperactivity in DAT-HET rats is leveled. The DAT-HET model leads to an increase in TH levels in nAcc. In addition, the free alcoholization reduces the level of TH in nAcc with the development of a pathological increase in TH, observed in the DAT-HET model, but has no effect on healthy animals. [ABSTRACT FROM AUTHOR]

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. Physiological and behavioral evaluations were conducted throughout the stress paradigm to determine if exercise blunts the effects of UCMS. Chronic stress induced voluntary wheel running (VWR) and weight loss in male and female mice. Compared to males, increased VWR was reported in females who also regained their weight lost by the end of the UCMS protocol. Exercise promoted resilience to stress-induced hyponeophagia in the novelty-suppressed feeding test and increased sucrose consumption. Exercise induced a sex-specific reduction in immobility and avoidance behavior in the tail suspension and open field tests and increased exploratory behavior in the light-dark test. These results indicate that exercise can promote resilience to the behavioral effects of chronic stress in males and females, and can affect behavior independent of chronic stress. [ABSTRACT FROM AUTHOR]

Brain-related comorbidities are frequently observed in chronic obstructive pulmonary disease (COPD) and are related to increased disease progression and mortality. To date, it is unclear which mechanisms are involved in the development of brainrelated problems in COPD. In this study, a cigarette smoke and lipopolysaccharide (LPS) exposure murine model was used to induce COPD-like features and assess the impact on brain and behavior. Mice were daily exposed to cigarette smoke for 72 days, except for days 42, 52, and 62, on which mice were intratracheally exposed to the bacterial trigger LPS. Emphysema and pulmonary inflammation as well as behavior and brain pathology were assessed. Cigarette smoke-exposed mice showed increased alveolar enlargement and numbers of macrophages and neutrophils in bronchoalveolar lavage. Cigarette smoke exposure resulted in lower body weight, which was accompanied by lower serum leptin levels, more time spent in the inner zone of the open field, and decreased claudin-5 and occludin protein expression levels in brain microvessels. Combined cigarette smoke and LPS exposure resulted in increased locomotion and elevated microglial activation in the hippocampus of the brain. These novel findings show that systemic inflammation observed after combined cigarette smoke and LPS exposure in this COPD model is associated with increased exploratory behavior. Findings suggest that neuroinflammation is present in the brain area involved in cognitive functioning and that blood-brain barrier integrity is compromised. These findings can contribute to our knowledge about possible processes involved in brain-related comorbidities in COPD, which is valuable for optimizing and developing therapy strategies. [ABSTRACT FROM AUTHOR]

Changes in the physiological and behavioral states of fish are affected by foreign substances. Therefore, fish need a certain adaptation period to eliminate the stress response. Herein, in order to determine the adaptation period, the bionic robot fish was used to obtain behavioral information about crucian carp, which was tested at five time points (1st, 7th, 14th, 21st and 28th day) within 28 days. First, the fear response and exploratory behavior of crucian carp affected by three-color bionic robot fish were explored. Then, according to the measurement results of the behavior, morphology, and feeding, and the physiological and biochemical properties of the crucian carp, a multi-parameter evaluation method was proposed to determine the adaptation period of the crucian carp under this monitoring mode. The results showed that more than 4 areas were occupied by crucian carp from the 21st day. From the 16th day, the number of crucian carp swimming with clear outlines gradually increased. The number of abnormal swimming occurrences decreased on day 13. More than 80% of the crucian carp body color returned to dark on the 23rd day. The crucian carp did not respond to food until day 19, when most of the crucian carp began to scramble for food. Food consumption reached more than two thirds on day 22. In addition, glucose and total protein leveled off after day 21, when mean hemoglobin levels were highest. Triglycerides showed a trend of first decreasing and then increasing. The pigmented area of the skin section gradually decreases and eventually stabilizes. In summary, it takes at least 23 days for the crucian carp to adapt to the influence of the bionic robot fish. [ABSTRACT FROM AUTHOR]

Adolescent intermittent ethanol (AIE) exposure in rodents has been shown to alter adult behavior in several domains, including learning and memory, social interaction, affective behavior, and ethanol self-administration. AIE has also been shown to produce non-specific behavioral changes that compromise behavioral efficiency. Many studies of these types rely on measuring behavior in mazes and other enclosures that can be influenced by animals' activity levels and exploratory behavior, and relatively few such studies have assessed sex as a biological variable. To address the effects of AIE and its interaction with sex on these types of behavioral assays, male and female adolescent rats (Sprague Dawley) were exposed to 10 doses of AIE (5 g/kg, intra-gastrically [i.g.]), or control vehicle, over 16 days (postnatal day [PND] 30-46), and then tested for exploratory and anxiety-like behaviors on the novelty-induced hypophagia (NIH) task in an open field, the elevated plus (EPM) maze, and the Figure 8 maze. AIE reduced activity/exploratory behaviors in males on the anxiety-producing NIH and EPM tasks, but reduced activity in both males and females in the Figure 8 maze, a task designed to create a safe environment and reduce anxiety. Independent of AIE, females engaged in more rearing behavior than males during the NIH task but less in the EPM, in which they were also less active than males. AIE also increased EPM open arm time in females but not in males. These findings demonstrate previously unrecognized sex differences in the effects of AIE on activity, exploratory behavior, and anxiety-like behavior; additionally, they underscore the need to design future behavioral studies of AIE using sex as a variable and with rigorous attention to how AIE alters these behaviors. [ABSTRACT FROM AUTHOR]

The high mobility group AT-hook 2 (HMGA2) protein works as an architectural regulator by binding AT-rich DNA sequences to induce conformational changes affecting transcription. Genomic deletions disrupting HMGA2 coding sequences and flanking noncoding sequences cause dwarfism in mice and rabbits. Here, CRISPR/Cas9 was used in mice to generate an Hmga2 null allele that specifically disrupts only the coding sequence. The loss of one or both alleles of Hmga2 resulted in reduced body size of 20% and 60%, respectively, compared to wild-type littermates as well as an allometric reduction in skull length in Hmga2-/- mice. Both male and female Hmga2-/- mice are infertile, whereas Hmga2+/- mice are fertile. Examination of reproductive tissues of Hmga2-/- males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed. Sperm analyses revealed severe oligospermia in mutant males and slightly decreased sperm viability, increased DNA damage but normal sperm chromatin compaction. Testis histology surprisingly revealed a normal seminiferous epithelium, despite the significant reduction in testis size. In addition, Hmga2-/- mice showed a significantly reduced exploratory behavior. In summary, the phenotypic effects in mouse using targeted mutagenesis confirmed that Hmga2 is affecting prenatal and postnatal growth regulation, male reproductive tissue development, and presents the first indication that Hmga2 function is required for normal mouse behavior. No specific effect, despite an allometric reduction, on craniofacial development was noted in contrast to previous reports of an altered craniofacial development in mice and rabbits carrying deletions of both coding and noncoding sequences at the 50 part of Hmga2. [ABSTRACT FROM AUTHOR]

Introduction: Decreased motivational tendency to seek out, engage in, and enjoy investing in complex cognitive processes in a sustained manner (need for cognition; NFC) may be a predictor and consequence of heightened anxiety and depression symptoms (ADS). However, the majority of investigations on this topic have been cross-sectional, which hinders causal inferences.Methods: The current study thus determined the within-person relations between NFC and ADS by using random intercept cross-lagged panel model (RI-CLPM) and bivariate dual latent change score (BLCS) approaches to separate between- and within-person effects. RI-CLPM and BLCS also present with advantages of adjusting for regression to the mean, baseline scores, autoregressive and lagged effects, and minimizing measurement error. Community-dwelling adults (n = 6750) completed the Mental Health Inventory-5 and trait-level NFC scales approximately every one year across 10 years.Results: RI-CLPM showed that within persons, lower level of NFC predicted higher future level of ADS, and vice versa (d = -0.852 to -0.498). Likewise, BLCS demonstrated that within persons, smaller change in NFC forecasted larger subsequent increase in ADS, and conversely (d = -0.631 to -0.519). Findings remained after adjusting for socio-demographic covariates.Conclusion: Consistent with theories, findings suggested that the within-person level-to-future level and change-to-future change relations among NFC and ADS were bi-directional and negative, with moderate-to-large effect sizes. Targeting NFC may treat or prevent the emergence of depression and anxiety disorders. Such efforts may include augmenting or personalizing evidence-based cognitive-behavioral therapeutic strategies for individuals with or at-risk for heightened ADS. [ABSTRACT FROM AUTHOR]

Goal-oriented behaviors of animals can be modeled by reinforcement learning algorithms. Such algorithms predict future outcomes of selected actions utilizing action values and updating those values in response to the positive and negative outcomes. In many models of animal behavior, the action values are updated symmetrically based on a common learning rate, that is, in the same way for both positive and negative outcomes. However, animals in environments with scarce rewards may have uneven learning rates. To investigate the asymmetry in learning rates in reward and non-reward, we analyzed the exploration behavior of mice in five-armed bandit tasks using a Q-learning model with differential learning rates for positive and negative outcomes. The positive learning rate was significantly higher in a scarce reward environment than in a rich reward environment, and conversely, the negative learning rate was significantly lower in the scarce environment. The positive to negative learning rate ratio was about 10 in the scarce environment and about 2 in the rich environment. This result suggests that when the reward probability was low, the mice tend to ignore failures and exploit the rare rewards. Computational modeling analysis revealed that the increased learning rates ratio could cause an overestimation of and perseveration on rare-rewarding events, increasing total reward acquisition in the scarce environment but disadvantaging impartial exploration. [ABSTRACT FROM AUTHOR]

The use of pesticides for plague control in agroecosystems generates a threat to wildlife and a major problem for human health. Pesticide compounds are also an important source of water and atmosphere contamination. Although insecticides are effective on their target organisms, they often affect organisms that are not their target. The aim of the present study was to research the effects of 3 types of neurotoxic insecticides—a pyrethroid (cypermethrin), a neonicotinoid (imidacloprid), and an organophosphate (chlorpyrifos)—on behavioral and physiological parameters of Pardosa saltans spider (Lycosidae). Our study analyzed for the first time the exploratory behavior of the spider mothers in the presence of these 3 insecticides on their egg‐sacs and also on the ground. We also evaluated the oxidative stress effects on the juveniles hatched in the egg‐sac protected by silk in relation to variations in detoxification enzymes (catalase, glutathione reductase, superoxide dismutase, glutathione‐S‐transferase, and glutathione peroxidase) and lipid peroxidation (reactive oxygen species [ROS]). The results show that these insecticides are repellents for mothers (cypermethrin is the most repellent), and maternal behavior is modified after detection of an insecticide on their egg‐sac but mothers do not abandon their egg‐sacs. These neurotoxic insecticides affect the juveniles inside their egg‐sac. Cypermethrin and chlorpyrifos caused more oxidative stress in juveniles than did imidacloprid. The ROS generated by these insecticides seemed to be adequately eliminated by the juveniles' antioxidant systems. Environ Toxicol Chem 2021;40:2861–2873. © 2021 SETAC [ABSTRACT FROM AUTHOR]

Introduction: Caloric restriction (CR) has been proven to promote a series of health benefits from yeast to primates. Nowadays, increasing rates of obesity certainly encourage researchers to evaluate CR effects and establish it as a therapeutic approach. Maternal obesity is also a concern, and studies in the developmental origins of health and disease (DOHaD) have shown the importance of interventions during pregnancy, especially those involving maternal nutrition. On the other hand, undernutrition during pregnancy leads to increased weight gain, disturbed feeding behavior and dysfunctional metabolism in adulthood. Methods: In this way, we utilized moderate CR (20% compared to control consumption) in pregnant Wistar rats as intervention, with malnutrition control by micronutrients supplementation. We assessed CR effects on offspring's developmental milestones, feeding behavior, exploratory behavior, and memory on adolescence (PND21) and adulthood (PND60). Results: We did not find alterations on litter size or birth weight, although CR pups were leaner at adult ages. Importantly, no delay in development was observed. Besides, female pups showed earlier suction reflex and male pups showed earlier response to the negative geotaxis. CR pups also showed less preference for palatable food (Froot Loops®) at adult age, which could be decisive on obesity tendency. Locomotor activity was increased by CR on PND60 and there was no effect on memory at all. Discussion: Our results on development and behavior demonstrate that gestational CR may be a helpful health strategy if malnutrition is well controlled, with potential clinical impact. [ABSTRACT FROM AUTHOR]

Abstract: Pain puts patients at risk for developing psychiatric conditions such as anxiety and depression. Preclinical mouse models of pain-induced affective behavior vary widely in methodology and results, impairing progress towards improved therapeutics. To systematically investigate the effect of long-term inflammatory pain on exploratory behavior and stress coping strategy, we assessed male C57BL/6J mice in the forced swim test (FST), elevated zero maze, and open field test at 4 and 6 weeks postinjection of Complete Freund's Adjuvant, while controlling for testing order and combination. Inflammatory pain did not induce a passive stress coping strategy in the FST and did not reduce exploratory behavior in the elevated zero maze or the open field test. Using systematic correlational analysis and composite behavioral scores, we found no consistent association among measures for mice with or without inflammatory pain. A meta-analysis of similar studies indicated a modest, significant effect of Complete Freund's Adjuvant on exploratory behavior, but not immobility in the FST, and high heterogeneity among effect sizes in all 3 paradigms. Given the urgency for understanding the mechanisms of pain comorbidities and identifying novel therapies, these findings support the reallocation of our limited resources away from such unreliable assays and toward motivated and naturalistic behaviors. Future studies in pain and psychiatric translational research may benefit by considering outcomes beyond binary categorization, quantifying the associations between multiple measured behaviors, and agnostically identifying subtle yet meaningful patterns in behaviors. [ABSTRACT FROM AUTHOR]

According to the two-hit hypothesis of psychoneuropathology formation, infectious diseases and other pathological conditions occurring during the critical periods of early ontogenesis disrupt normal brain development and increase its susceptibility to stress experienced in adolescence and adulthood. It is believed that these disorders are associated with changes in the functional activity of the glutamatergic system in the hippocampus. Here, we studied expression of NMDA (GluN1, GluN2a, GluN2b) and AMPA (GluA1, GluA2) glutamate receptor subunits, as well as glutamate transporter EAAT2, in the ventral and dorsal regions of the hippocampus of rats injected with LPS during the third postnatal week and then subjected to predator stress (contact with a python) in adulthood. The tests were performed 25 days after the stress. It was found that stress altered protein expression in the ventral, but not in the dorsal hippocampus. Non-stressed LPS-treated rats displayed lower levels of the GluN2b protein in the ventral hippocampus vs. control animals. Stress significantly increased the content of GluN2b in the LPS-treated rats, but not in the control animals. Stress also affected differently the exploratory behavior of LPS-injected and control rats. Compared to the non-stressed animals, stressed control rats demonstrated a higher locomotor activity during the 1st min of the open field test, while the stressed LPS-injected rats displayed lower locomotor activity than the non-stressed rats. In addition, LPS-treated stressed and non-stressed rats spent more time in the open arms of the elevated plus maze and demonstrated reduced blood levels of corticosterone. To summarize the results of our study, exposure to bacterial LPS in the early postnatal ontogenesis affects the pattern of stress-induced changes in the behavior and hippocampal expression of genes coding for ionotropic glutamate receptor subunits after psychogenic trauma suffered in adulthood. [ABSTRACT FROM AUTHOR]

Curiosity and intent to use alcohol in pre-adolescence is a risk factor for later experimentation and use, yet we know little of how curiosity about use develops. Here, we examine factors that may influence curiosity about alcohol use, as it may be an important predictor of later drinking behavior. Cross-sectional data on youth ages 10-11 from the ongoing Adolescent Brain Cognitive Development℠ (ABCD) Study Year 1 follow-up were used (n = 2,334; NDA 2.0.1). All participants were substance-naïve at time of assessment. Group factor analysis identified latent factors across common indicators of risk for early substance use (i.e., psychopathology and trait characteristics; substance use attitudes/behaviors; neurocognition; family and environment). Logistic mixed-effect models tested associations between latent factors of risk for early substance use and curiosity about alcohol use, controlling for demographics and study site. Two multidimensional factors were significantly inversely and positively associated with greater curiosity about alcohol use, respectively: 1) low internalizing and externalizing symptomatology coupled with low impulsivity, perceived neighborhood safety, negative parental history of alcohol use problems, and fewer adverse life experiences and family conflict; and 2) low perceived risk of alcohol use coupled with lack of peer disapproval of use. When assessing all risk factors in an overall regression, lack of perceived harm from trying alcohol once or twice was associated with greater likelihood of alcohol curiosity. Taken together, perceptions that alcohol use causes little harm and having peers with similar beliefs is related to curiosity about alcohol use among substance-naïve 10-11-year-olds. General mental health and environmental risk factors similarly increase the odds of curiosity for alcohol. Identification of multidimensional risk factors for early alcohol use may point to novel prevention and early intervention targets. Future longitudinal investigations in the ABCD cohort will determine the extent to which these factors and curiosity predict alcohol use among youth. [ABSTRACT FROM AUTHOR]

• Maternal prebiotic intake in mice alters offspring behavior and brain gene expression. • Perinatal prebiotic consumption changes the offspring gut microbiome. • Prebiotic intake while nursing increases fecal butyrate and propionate in offspring. • Consuming a prebiotic perinatally may influence offspring brain development. Compelling evidence links enteric microbes to brain function and behavior. Galacto-oligosaccharide prebiotics have been shown to modulate the composition of gut flora and induce metabolic, neurochemical, and behavioral changes in adult rodents. Despite the brain being most susceptible to environmental factors, such as nutrients and toxins, during the earliest stages of development, it is unknown whether maternal prebiotic supplementation during gestation and lactation influences the offspring gut microbiome, brain, or behavior. The aim of this study was to test whether maternal galacto-oligosaccharide intake during pregnancy and lactation alters the brain and behavior in naïve and endotoxin-challenged offspring. CD1 female mice received either normal drinking water or water supplemented with Bimuno® galacto-oligosaccharides (B-GOS) during gestation and suckling. Offspring behavior was tested at weaning age or adulthood, and a cross-foster design was employed in a separate cohort to differentiate between effects of prenatal and postnatal maternal B-GOS intake. Lipopolysaccharide was also administered to pups at postnatal day 9 to determine whether maternal B-GOS influences the neurobiological and behavioral effects of a neonatal pro-inflammatory challenge in adulthood. Fecal microbiome composition and metabolites were analyzed to explore potential relationships between the maternal microbiome, the offspring gut microbiome, and the offspring brain and behavior. Maternal B-GOS supplementation increased exploratory behavior and reduced expression of hippocampal glutamate receptor genes in young, weaning-age offspring. In addition, postnatal, but not prenatal, B-GOS supplementation increased fecal butyrate and propionate levels. Finally, in adult offspring, perinatal B-GOS intake increased cortical glutamate receptor subunits in females, increased social preference, and reduced anxiety. We provide novel and comprehensive evidence for the influence of maternal prebiotic intake on offspring behavior, brain gene expression, and gut microbiome composition in mice. [ABSTRACT FROM AUTHOR]

The subjective nature of human emotions makes them uniquely challenging to investigate in preclinical models. While behavioral assays in rodents aim to evaluate affect (i.e., anxiety, hypervigilance), they often lack ethological validity. Playback of negatively valenced 22-kHz ultrasonic vocalizations (USVs) in rats shows promise as a translational tool to investigate affective processing. Much like how human facial expressions can communicate internal states, rats emit 22-kHz USVs that similarly convey negative affective states to conspecifics indicating possible threat. 22-kHz USV playback elicits avoidance and hypervigilant behaviors, and recruit brain regions comparable to those seen in human brains evoked by viewing fearful faces. Indeed, 22-kHz playback alters neural activity in brain regions associated with negative valence systems (i.e., amygdala, bed nucleus of the stria terminalis, periaqueductal gray) alongside increases in behaviors typically associated with anxiety. Here, we present evidence from the literature that supports leveraging 22-kHz USV playback in rat preclinical models to obtain clinically relevant and translational findings to identify the neural underpinnings of affective processing and neuropathological dysfunction. • Rat 22-kHz USV playback can be used to translationally assess threat processing. • Aversive USV playback leads to decreased approach and exploratory behavior. • 22-kHz USVs activate negative valence systems comparable to human fearful face task. • 22-kHz USV playback can provide a window into pathological threat assessment. [ABSTRACT FROM AUTHOR]

Serotonin 5-HT2A receptors and the brain-derived neurotrophic factor (BDNF) are involved in the pathophysiology and treatment of many psychiatric diseases. However, the interaction between 5-HT2A and BDNF is still poorly understood. In the present paper, the effects of chronic treatment with mixed 5-HT2A/2C receptor agonist DOI, highly selective 5-HT2A agonists TCB-2 and 25CN-NBOH on behavior and the BDNF system have been investigated. Chronic treatment of males of C57Bl/6 mice with DOI, TCB-2 and 25CN-NBOH (1 mg/kg, i.p., 14 days) resulted in desensitization of 5-HT2A receptors. Treatment with 25CN-NBOH significantly increased startle amplitude. At the same time all used drugs failed to affect anxiety, exploratory and stereotyped behavior as well as spatial memory and learning. TCB-2 and 25CN-NBOH increased the BDNF mRNA level. All 5-HT2A agonists increased the proBDNF level but failed to alter the mature BDNF protein level. TrkB and p75NTR mRNA levels were affected by all utilized agonists. All drugs decreased the total level as well as membrane TrkB protein one indicating downregulation of TrkB receptors. All agonists decreased the membrane p75NTR protein level. Thus, we have shown for the first time that the chronic activation of the 5-HT2A receptor with agonists has affected the BDNF system almost on all levels—transcription, proBDNF production, TrkB and p75NTR receptors' level. The obtained data suggested possible suppression in BDNF-TrkB signaling under chronic treatment with 5-HT2A agonists. [ABSTRACT FROM AUTHOR]

P2X2 and P2X3 receptors are widely expressed in both the peripheral nervous system and the central nervous system and have been proven to participate in different peripheral sensory functions, but there are few studies on the involvement of P2X2 and P2X3 receptors in animal behaviors. Here we used P2X2 and P2X3 knockout mice to address this issue. P2X2 knockout mice showed normal motor function, exploratory behavior, anxiety‐like behaviors, learning and memory behaviors and passive coping response to behavioral challenge. Nevertheless, the effect of ATP infusion in the medial prefrontal cortex (mPFC) on the passive coping response was blocked by P2X2 but not P2X3 receptor deletion. Additionally, no deficits in a wide variety of behavioral tests were observed in P2X3 knockout mice. These findings demonstrate a role of P2X2 receptor in the mPFC in adenosine‐5′‐triphosphate modulation of the passive coping response to behavioral challenge and show that the P2X2/P2X3 receptor is dispensable for behaviors. [ABSTRACT FROM AUTHOR]

• Chemotherapy increases IL-6 within the brain and alters depressive-like behavior. • Social housing attenuates chemotherapy-induced CNS alterations. • Oxytocin administration ameliorates IL-6 expression and depressive-like behavior. • Oxytocin antagonist administration increases IL-6 expression and depressive-like behavior. Breast cancer survivors receiving chemotherapy often report increased anxiety and depression. However, the mechanism underlying chemotherapy-induced changes in affect remains unknown. We hypothesized that chemotherapy increases cytokine production, in turn altering exploratory and depressive-like behavior. To test this hypothesis, female Balb/C mice received two injections, separated by two weeks, of vehicle (0.9% saline) or a chemotherapeutic cocktail [9 mg/kg doxorubicin (A) and 90 mg/kg cyclophosphamide (C)]. Peripheral and central cytokine concentrations were increased one and seven days, respectively, after AC. Because of the beneficial effects of social enrichment on several diseases with inflammatory components, we examined whether social enrichment could attenuate the increase in peripheral and central cytokine production following chemotherapy administration. Socially isolated mice receiving AC therapy demonstrated increased depressive-like and exploratory behaviors with a concurrent increase in hippocampal IL-6. Whereas, group housing attenuated AC-induced IL-6 and depressive-like behavior. Next, we sought to determine whether central oxytocin may contribute to the protective effects of social housing after AC administration. Intracerebroventricular administration of oxytocin to socially isolated mice recapitulated the protective effects of social enrichment; specifically, oxytocin ameliorated the AC-induced effects on IL-6 and depressive-like behavior. Furthermore, administration of an oxytocin antagonist to group housed mice recapitulated the responses of socially isolated mice; specifically, AC increased depressive-like behavior and central IL-6. These data suggest a possible neuroprotective role for oxytocin following chemotherapy, via modulation of IL-6. This study adds to the growing literature detailing the negative behavioral effects of chemotherapy and provides further evidence that social enrichment may be beneficial to health. [ABSTRACT FROM AUTHOR]

are a recently-identified set of basic perceptions about the general character of reality (e.g. the world is boring) thought to have many psychological implications. This article explores implications relevant to wellbeing and positive intervention research. After summarizing the supposed general function of primal world beliefs, I specify ten hypotheses concerning gratitude, curiosity, optimism, trust, self-efficacy, positive emotions, engagement, meaning, life satisfaction, and overall wellbeing. Each variable may involve behavioral patterns that present as trait-like personality characteristics while actually being context-specific reactions to underlying (and malleable) perceptions. Experimental research could test these hypotheses by (a) examining whether primal world beliefs partially mediate the wellbeing impact of established interventions such as Three Good Things and (b) creating novel interventions specifically targeting primal world beliefs. To foster the latter, I discuss elements that novel interventions might incorporate, illustrating with an example called the Leaf Exercise. [ABSTRACT FROM AUTHOR]

Rationale: Νeurosteroids, like dehydroepiandrosterone (DHEA), play an important role in neurodegeneration and neural protection, but they are metabolized in androgens, estrogens, or other active metabolites. A newly developed synthetic DHEA analog, BNN27 ((20R)-3β,21-dihydroxy-17R,20-epoxy-5-pregnene), exerts neurotrophic and neuroprotective actions without estrogenic or androgenic effects. Objectives: This study aimed to investigate potential anxiolytic or antidepressant properties of BNN27. Methods: Male and female adult Wistar rats were treated with BNN27 (10, 30, or 90 mg/kg, i.p.) and subjected to behavioral tests measuring locomotion, exploration, and "depressive-like" behavior (open field, light/dark box, hole-board, and forced swim tests). The hippocampus and prefrontal cortex were collected for glutamate and GABA measurements, and trunk blood was collected for gonadal hormone analysis. Results: Acute high-dose BNN27 reduced locomotion and exploratory behavior in both sexes. Intermediate acute doses (30 mg/kg) of BNN27 reduced exploration and testosterone levels only in males, and enhanced progesterone levels in both sexes. Notably, with the present design, BNN27 had neither anxiolytic nor antidepressant effects and did not affect estrogen levels. Interestingly, acute administration of a low BNN27 dose (10 mg/kg) increased glutamate turnover, GABA, and glutamine levels in the hippocampus. The same dose also enhanced glutamate levels in the prefrontal cortex of males only. Sex differences were apparent in the basal levels of behavioral, hormonal, and neurochemical parameters, as expected. Conclusions: BNN27 affects locomotion, progesterone, and testosterone levels, as well as the glutamatergic and GABAergic systems of the hippocampus and prefrontal cortex in a sex-dependent way. [ABSTRACT FROM AUTHOR]

Uncontrollable stress precipitates negative mental and physical health outcomes. Furthermore, the vicarious experience of stress (e.g. observing another individual experience a direct stressor) can mimic the effects of directly experiencing the stressor. The current experiment examined the behavioral and physiological effects of the vicarious experience of stress using the socially monogamous prairie vole. Male prairie voles were exposed to either an empty open field chamber, or a chamber in which the animal observed a sibling undergoing a concurrent direct physical stressor (tail suspension test) for five minutes. Exploratory and anxiety-like behaviors were recorded in all observers during the test session. Cardiac indices of heart rate and heart rate variability were recorded in a subset of observers prior to, during, and following the test session. Corticosterone levels were measured in all observers and siblings following the test session. When compared to animals exposed to an empty open field chamber, animals that observed a sibling undergo a direct physical stressor exhibited increased heart rate and circulating corticosterone, and decreased heart rate variability. These physiological stress indicators were supported by behavioral changes, including increased freezing followed immediately by orienting of the head toward the center of the apparatus, and decreased locomotion, grooming, and rearing. These preliminary results suggest that prairie voles experience stress vicariously, and provide a foundation for additional studies focused on the underlying mechanisms of vicarious stress. The use of this model may inform our understanding of the social transmission of stress among social species, including humans. The experience of stress, including observing stress in a loved one, has negative consequences on mental and physical health. This study used a social rodent (prairie voles) to demonstrate that stress transfers among social individuals, consequently producing an increased physiological and behavioral stress response in prairie voles observing their siblings experience stress. This research informs our understanding of the interactions of social experiences and stress in humans. [ABSTRACT FROM AUTHOR]

Drawing on Cognitive Appraisal and Job Demands-Resources (JD-R) theories, this study examines how job stress and work-related curiosity may affect employee's innovative behavior. The study utilized two-wave longitudinal data collected from 311 frontline employees from five-star hotels in the UAE. The study found that employees who demonstrated curiosity about different aspects of their work were more likely to engage in innovative behavior. On the other hand, stress was observed to have a different effect. The negative effect of job stress on innovative behavior tended to become positive and significant when curiosity was part of the response to stress. [ABSTRACT FROM AUTHOR]

Animals can navigate an environment relying on different sources of information, such as geometrical or featural cues. The favoring of one type of information over another depends on multiple factors, such as inter-individual differences in behavior and cognition. Free-range chickens present different range use patterns, which may be explained by behavioral and cognitive differences. However, how behavior, cognition, and range use intercorrelate is still poorly understood. In this work, we aimed to further understand possible differences in behavior and cognition between two groups of free-range broiler chickens: those who frequently explore their range ('high rangers') and those who prefer to stay in or near the barn ('low rangers'). Prior to range access, individual behavior was measured in open field-, emergence-, and social motivation tests. To investigate cognitive differences, we analyzed whether exploratory behavior was linked to different performances in the use of distal and local spatial cues during an orientation task. During the social motivation test, low rangers showed a higher inclination to be near conspecifics than did high rangers. Our orientation tests show that chickens preferred to orientate themselves using the local cues over the distal cues. Individual differences were only found for distal, but not for local, cue use suggesting that demanding tasks are more efficient in revealing individual cognitive differences. Our results suggest that considering variation in social motivation may allow a more comprehensive understanding of chicken range use. Our results also support the importance of incorporating multiple aspects of individual differences to understand individual reactions to its environment. [ABSTRACT FROM AUTHOR]

Introduction: Depression is characterized by behavioral, cognitive and physiological changes, imposing a major burden on the overall wellbeing of the patient. Some evidence indicates that social stress, changes in growth factors (e.g., brain-derived neurotrophic factor (BDNF)), and neuroinflammation are involved in the development and progression of the disease. The monoamine oxidase A inhibitor drug harmine was suggested to have both antidepressant and anti-inflammatory properties and may, therefore, be a potential candidate for treatment of depression. Aim: The goal of this study was to assess the effects of harmine on behavior, brain BDNF levels, and microglia activation in control rats and a rat model of social stress. Material and methods: Rats were submitted to 5 consecutive days of repeated social defeat (RSD) or control conditions. Animals were treated daily with harmine (15 mg/kg) or vehicle from day 3 until the end of the experiment. To assess the effects of harmine treatment on behavior, the sucrose preference test (SPT) was performed on days 1, 6, and 15, the open field test (OFT) on days 6 and 14, and the novel object recognition test (NOR) on day 16. Brain microgliosis was assessed using [11C]PBR-28 PET on day 17. Animals were terminated on day 17, and BDNF protein concentrations in the hippocampus and frontal cortex were analyzed using ELISA. Results: RSD significantly decreased bodyweight and increased anxiety and anhedonia-related parameters in the OFT and SPT on day 6, but these behavioral effects were not observed anymore on day 14/15. Harmine treatment caused a significant reduction in bodyweight gain in both groups, induced anhedonia in the SPT on day 6, and significantly reduced the mobility and exploratory behavior of the animals in the OFT mainly on day 14. PET imaging and the NOR test did not show any significant effects on microglia activation and memory, respectively. BDNF protein concentrations in the hippocampus and frontal cortex were not significantly affected by either RSD or harmine treatment. Discussion: Harmine was not able to reverse the acute effects of RSD on anxiety and anhedonia and even aggravated the effect of RSD on bodyweight loss. Moreover, harmine treatment caused unexpected side effects on general locomotion, both in RSD and control animals, but did not influence glial activation status and BDNF concentrations in the brain. In this model, RSD-induced stress was not strong enough to induce long-term effects on the behavior, neuroinflammation, or BDNF protein concentration. Thus, the efficacy of harmine treatment on these delayed parameters needs to be further evaluated in more severe models of chronic stress. [ABSTRACT FROM AUTHOR]

Over long evolutionary timescales, major changes to the copy number, function, and genomic organization of genes occur, however, our understanding of the individual mutational events responsible for these changes is lacking. In this report, we study the genetic basis of adaptation of two strains of C. elegans to laboratory food sources using competition experiments on a panel of 89 recombinant inbred lines (RIL). Unexpectedly, we identified a single RIL with higher relative fitness than either of the parental strains. This strain also displayed a novel behavioral phenotype, resulting in higher propensity to explore bacterial lawns. Using bulk-segregant analysis and short-read resequencing of this RIL, we mapped the change in exploration behavior to a spontaneous, complex rearrangement of the rcan-1 gene that occurred during construction of the RIL panel. We resolved this rearrangement into five unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to human RCAN1/DSCR1 calcipressin gene, which has been implicated as a causal gene for Down syndrome. The genomic rearrangement in rcan-1 creates two complete and two truncated versions of the rcan-1 coding region, with a variety of modified 5' and 3' non-coding regions. While most copy-number variations (CNVs) are thought to act by increasing expression of duplicated genes, these changes to rcan-1 ultimately result in the reduction of its whole-body expression due to changes in the upstream regions. By backcrossing this rearrangement into a common genetic background to create a near isogenic line (NIL), we demonstrate that both the competitive advantage and exploration behavioral changes are linked to this complex genetic variant. This NIL strain does not phenocopy a strain containing an rcan-1 loss-of-function allele, which suggests that the residual expression of rcan-1 is necessary for its fitness effects. Our results demonstrate how colonization of new environments, such as those encountered in the laboratory, can create evolutionary pressure to modify gene function. This evolutionary mismatch can be resolved by an unexpectedly complex genetic change that simultaneously duplicates and diversifies a gene into two uniquely regulated genes. Our work shows how complex rearrangements can act to modify gene expression in ways besides increased gene dosage. Author summary: Evolution acts on genetic variants that modify phenotypes that increase the likelihood of staying alive and passing on these genetic changes to subsequent generations (i.e. fitness). There is general interest in understanding the types of genetic variants that can increase fitness in specific environments. One route that fitness can be increased is through changes in behavior, such as finding new food sources. Here, we identify a spontaneous genetic change that increases exploration behavior and fitness of animals in laboratory environments. Interestingly, this genetic change is not a simple genetic change that deletes or changes the sequence of a protein product, but rather a complex structural variant that simultaneously duplicates the rcan-1 gene and also modifies its expression in a number of tissues. Our work demonstrates how a complex structural change can duplicate a gene, modify the DNA control regions that determine its cellular sites of action, and confer a fitness advantage that could lead to its spread in a population. [ABSTRACT FROM AUTHOR]

Asymmetries in bilateral organisms attract a lot of curiosity given that they are conspicuous departures from the norm. They allow the investigation of the integration at different levels of biological organization. Here we study whether and how behavioral and asymmetrical anatomical traits co-evolved and work together. We ask if asymmetry is determined locally for each trait or at a whole individual level in a species bearing conspicuous asymmetrical genitalia. Asymmetric genitalia evolved in many species; however, in most cases the direction of asymmetry is fixed. Therefore, it has been rarely determined if there is an association between the direction of asymmetry in genitalia and other traits. In onesided livebearer fish of the genus Jenynsia (Cyprinodontiformes, Anablepidae), the anal fin of males is modified into a gonopodium, an intromittent organ that serves to inseminate females. The gonopodium shows a conspicuous asymmetry, with its tip bending either to the left or the right. By surveying 13 natural populations of Jenynsia lineata , we found that both genital morphs are equally common in wild populations. In a series of experiments in a laboratory population, we discovered asymmetry and lateralization for multiple other traits; yet, the degree of integration varied highly among them. Lateralization in exploratory behavior in response to different stimuli was not associated with genital morphology. Interestingly, the direction of genital asymmetry was positively correlated with sidedness of mating preference and the number of neuromasts in the lateral line. This suggests integration of functionally linked asymmetric traits; however, there is no evidence that asymmetry is determined at the whole individual level in our study species. [ABSTRACT FROM AUTHOR]

• Mice deficient of β5i/LMP7 display normal locomotor and exploratory activity in basic behavioral paradigms. • There is no effect of β5i/LMP7 deficiency on anxiety behavior in general. • β5i/LMP7-deficiency does not affect predator odor-induced defensive behavior, startle magnitudes and prepulse inhibition. • Depletion of β5i/LMP7 leads to increased anxiety after mild stress. • β5i/LMP7-deficient mice show no differences in contextual fear but increased cued fear conditioning compared to wildtype littermates. Proteolysis as mediated by one of the major cellular protein degradation pathways, the ubiquitin–proteasome system (UPS), plays an essential role in learning and memory formation. However, the functional relevance of immunoproteasomes in the healthy brain and especially their impact on normal brain function including processes of learning and memory has not been investigated so far. In the present study, we analyzed the phenotypic effects of an impaired immunoproteasome formation using a β5i/LMP7-deficient mouse model in different behavioral paradigms focusing on locomotor activity, exploratory behavior, innate anxiety, startle response, prepulse inhibition, as well as fear and safety conditioning. Overall, our results demonstrate no strong effects of constitutive β5i/LMP7-deficiency on gross locomotor abilities and anxiety-related behavior in general. However, β5i/LMP7-deficient mice expressed more anxiety after mild stress and increased cued fear after fear conditioning. These findings indicate that the basal proper formation of immunoproteasomes and/or at least the expression of β5i/LMP7 in healthy mice seem to be involved in the regulation of anxiety and cued fear levels. [ABSTRACT FROM AUTHOR]

Collared (Dicrostonyx groenlandicus) and brown (Lemmus trimucronatus) lemmings coexist in tundra habitats across much of the middle and lower Canadian arctic. Their coexistence, and response to predation risk, appears mediated by behavior. We analyzed field-collected videos of open-field tests to assess potential differences in innate behaviors between the two species. Collared lemmings were less active and exhibited less exploratory behavior than did brown lemmings, which were more active under cover than in the open. Similar behaviors scaling along axes of activity and curiosity were revealed by principal components analysis. Each axis defined different aspects of brown lemming personality, but repeated testing of the same individuals yielded a striking dependence of their behavioral response on open-field treatments. Even so, the differences between species in behavior correlate well with their habitat preferences that resolve competition and govern their coexistence. [ABSTRACT FROM AUTHOR]

Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats. Here, we aimed to create a temporal profile of the neurobehavioral and neuropathological effects of a single ACHI. Adolescent male rats were placed in a restraint bag and a steel helmet was positioned over the head such that the impact target was centered over the left parietal cortex. Once positioned on a foam platform, a cortical impactor was used to strike the helmet. Sham animals underwent the same procedure without impact. When compared with sham rats, those given a single ACHI displayed evidence of sensorimotor deficits and reduced exploratory behavior within the first 20 min post-injury; however, these effects were resolved after 24 h. A single ACHI impaired spatial memory on the Y-maze task at both 5 min and 24 h post-ACHI; however, no deficits were apparent at 48 h. Immunostaining revealed region-specific increases in ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein expression at 3 days post-impact, with no differences found at either 1 or 14 days. Taken together, our findings indicate that a single ACHI results in transient neurobehavioral and glial disturbances and as such, this model may be a valuable tool for pre-clinical concussion research. [ABSTRACT FROM AUTHOR]

Infants from low-income households typically spend less time exploring objects and use less mature strategies when they do explore compared to their higher-income peers (e.g., Clearfield et al., 2014). The current study tested a novel intervention designed to boost early object exploration in infants from low-income households. The intervention, called Play for Success, was administered through the Early Head Start home visiting program, and asked all infants to explore a toy with a caregiver for 10 min a day every day for two weeks. Forty-two 6- to 10-month-old infants were randomly assigned to one of three intervention groups: Social (unstructured direction), Teach Two (simple structured direction), or Teach Many (complex structured direction). Infants' exploratory behaviors were tested three times: before the intervention, immediately following, and again four weeks later. The results demonstrated that only infants in Teach 2 maintained their level of exploration at both the post-test and 4 weeks later while infants in the other groups showed significant decreases in exploration over time. These results suggest that Play for Success is a promising new intervention, but only in the condition that included repeated simple structured direction. [ABSTRACT FROM AUTHOR]

In humanitarian emergency settings there is need for low cost and rapidly deployable interventions to protect vulnerable children, in- and out-of-school, from diarrhoeal diseases. Handwashing with soap can greatly reduce diarrhoea but interventions specifically targeting children's handwashing behaviour in humanitarian settings have not been tested. Traditional children's handwashing promotion interventions have been school-focused, resource-intensive and reliant on health-based messaging. However, recent research from non-humanitarian settings and targeting adults suggests that theory-based behaviour change interventions targeting specific motives may be more effective than traditional handwashing interventions. In this proof-of-concept study we test, for the first time, the distribution of a modified soap bar, designed to appeal to the motives of play and curiosity, in a household-level, rapidly deployable, handwashing promotion intervention for older children in a humanitarian setting - an internally displaced persons camp in Iraqi Kurdistan. Out of five total blocks within the camp, one was assigned to intervention and one to control. 40 households from each assigned block were then randomly chosen for inclusion in the study and the practice of handwashing with soap at key times was measured at baseline and four weeks after intervention delivery. Children in intervention households received transparent soaps with embedded toys, delivered within a short, fun, and interactive household session with minimal, non-health-based, messaging. The control group received plain soap delivered in a short standard, health-based, hygiene promotion session. At the 4-week follow-up, children in the intervention group were 4 times more likely to wash their hands with soap after key handwashing occasions than expected in the counterfactual (if there had been no intervention) based on the comparison to children in the control group (adjusted RR = 3.94, 95% CI 1.59-9.79). We show that distributing soaps with toys embedded inside, in a rapidly deployable intervention, can improve child handwashing behaviour in a humanitarian emergency context. Further studies are needed to determine the longer-term behavioural and health impact of such an intervention when delivered at a greater scale in a humanitarian context. [ABSTRACT FROM AUTHOR]

Honeybees, Apis mellifera, perform re-orientation flights to learn about the new surroundings of the hive when their hive is transported to a new location. Since the pattern of re-orientation flights has not yet been studied, we asked whether this form of exploratory behavior differs from the well described exploratory orientation flights performed by young honeybees before they start foraging. We also investigated whether the exploratory components of re-orientation flights differ from foraging flights and if so how. We recorded re-orientation flights using harmonic radar technology and compared the patterns and flight parameters of these flights with the first exploratory orientation flights of young honeybees and foraging flights of experienced foragers. Just as exploratory orientation flights of young honeybees, re-orientation flights can be classified into short- and long-range flights, and most short-range re-orientation flights were performed under unfavorable weather conditions. This indicates that bees adapt the flight pattern of their re-orientation and orientation flights to changing weather conditions in a similar way. Unlike exploratory orientation flights, more than one sector of the landscape was explored during a long-range re-orientation flight, and significantly longer flight durations and flight distances were observed. Thus, re-orienting bees explored a larger terrain than bees performing their first exploratory orientation flight. By displacing some bees after their first re-orientation flight, we could demonstrate that a single re-orientation flight seems to be sufficient to learn the new location of the hive. The flight patterns of re-orientation flights differed clearly from those of foraging flights. Thus, re-orientation flights represent a special exploratory behavior that is triggered by a change in the location of the hive. [ABSTRACT FROM AUTHOR]

Behavior is shaped by both the internal state of an animal and its individual behavioral biases. Rhythmic variation in gonadal hormones during the estrous cycle is a defining feature of the female internal state, one that regulates many aspects of sociosexual behavior. However, it remains unclear whether estrous state influences spontaneous behavior and, if so, how these effects might relate to individual behavioral variation. Here, we address this question by longitudinally characterizing the open-field behavior of female mice across different phases of the estrous cycle, using unsupervised machine learning to decompose spontaneous behavior into its constituent elements. 1,2,3,4 We find that each female mouse exhibits a characteristic pattern of exploration that uniquely identifies it as an individual across many experimental sessions; by contrast, estrous state only negligibly impacts behavior, despite its known effects on neural circuits that regulate action selection and movement. Like female mice, male mice exhibit individual-specific patterns of behavior in the open field; however, the exploratory behavior of males is significantly more variable than that expressed by females both within and across individuals. These findings suggest underlying functional stability to the circuits that support exploration in female mice, reveal a surprising degree of specificity in individual behavior, and provide empirical support for the inclusion of both sexes in experiments querying spontaneous behaviors. • Spontaneous behavior of female mice is only negligibly affected by estrous state • Females and males exhibit strongly individualized patterns of exploration • Female spontaneous behavior is less variable than male behavior Levy et al. track open-field behavior of female mice over weeks and find that behavior reflects individual identity far more than estrous state. Open-field exploration patterns in males are much more variable than in females, arguing for the inclusion of both sexes in studies of spontaneous behaviors. [ABSTRACT FROM AUTHOR]

Since the origins of psychology, curiosity has occupied a pivotal position in the study of motivation, emotion, and cognition; and disciplines as far-ranging as biology, economics, robotics, and leadership. Theorists have disagreed about the basic tenets of curiosity; some researchers contend that the rewards arise when resolving ambiguity and uncertainty whereas others argue that being curious is an intrinsically pleasurable experience. Three studies were conducted to consolidate competing theories and isolated bodies of research. Using data from a community survey of 508 adults (Study 1), 403 adults on MTurk (Study 2), and a nationally representative household survey of 3,000 adults (Study 3), we found evidence for five distinct factors: Joyous Exploration, Deprivation Sensitivity, Stress Tolerance, Social Curiosity, and Thrill Seeking - forming The Five-Dimensional Curiosity Scale (5DC). Each factor had substantive relations with a battery of personality, emotion, and well-being measures. Taking advantage of this multidimensional model, we found evidence for four distinct types of curious people in Study 3 referred to as The Fascinated (28% of sample), Problem Solvers (28%), Empathizers (25%), and Avoiders (19%). Subgroups differed in their passionate interests, areas of expertise, consumer behavior, and social media use; challenging an assumption that there is a homogenous population to be discriminated on a single dimension from incurious to very curious. With greater bandwidth and predictive power, the 5DC offers new opportunities for research on origins, consequences, life outcomes, and intervention strategies to enhance curiosity. [ABSTRACT FROM AUTHOR]

Ample studies have shown that housing can affect the health, welfare and behavior of mice and therefore, the outcomes of certain experiments. The aim of this study was to investigate if three widely used housing systems, Open Top Cages (OTC), Motor Free Ventilated Cages (MFVC) and Individually Ventilated Cages (IVC) may affect exploratory and anxiety-related behaviors in mice. Subjects were 8 week-old male C57Bl/6 J mice (n = 36) divided into three groups, OTC, IVC and MFVC groups, respectively. The experimental procedure consisted of two behavioral tests: the open field and the elevated plus maze test. Although there were no differences in the open field test, the results from the elevated plus maze showed that animals housed in the MFVCs exhibited increased exploratory and less anxiety-like behavior. It is concluded that the different caging systems may have an impact on the outcome of behavioral tests used to assess exploratory and anxiety like behavior in mice. Therefore, it is essential to take into consideration housing conditions when reporting, analyzing, and/or systematically reviewing the results of behavioral testing in mice. [ABSTRACT FROM AUTHOR]

This paper examined, with a behavioral paradigm, to what extent people choose to view stimuli that portray death, violence or harm. Based on briefly presented visual cues, participants made choices between highly arousing, negative images and positive or negative alternatives. The negative images displayed social scenes that involved death, violence or harm (e.g., war scene), or decontextualized, close-ups of physical harm (e.g., mutilated face) or natural threat (e.g., attacking shark). The results demonstrated that social negative images were chosen significantly more often than other negative categories. Furthermore, participants preferred social negative images over neutral images. Physical harm images and natural threat images were not preferred over neutral images, but were chosen in about thirty-five percent of the trials. These results were replicated across three different studies, including a study that presented verbal descriptions of images as pre-choice cues. Together, these results show that people deliberately subject themselves to negative images. With this, the present paper demonstrates a dynamic relationship between negative information and behavior and advances new insights into the phenomenon of morbid curiosity. [ABSTRACT FROM AUTHOR]

Curiosity plays a key role in directing learning throughout the lifespan. Prior work finds that violations of expectations can be powerful triggers of curiosity in both children and adults, but it is unclear which expectation-violating events induce the greatest curiosity and how this might vary over development. Some theories have suggested a U-shaped function such that stimuli of moderate extremity pique the greatest curiosity. However, expectation-violations vary not only in degree, but in kind: for example, some things violate an intuitive theory (e.g., an alligator that can talk) and others are merely unlikely (e.g., an alligator hiding under your bed). Combining research on curiosity with distinctions posited in the cognitive science of religion, we test whether minimally counterintuitive (MCI) stimuli, which involve one violation of an intuitive theory, are especially effective at triggering curiosity. We presented adults (N = 77) and 4- and 5-year-olds (N = 36) in the United States with stimuli that were ordinary, unlikely, MCI, and very counterintuitive (VCI) and asked which one they would like to learn more about. Adults and 5-year-olds chose Unlikely over Ordinary and MCI over Unlikely, but not VCI over MCI, more often than chance. Our results suggest that (i) minimally counterintuitive stimuli trigger greater curiosity than merely unlikely stimuli, (ii) surprisingness has diminishing returns, and (iii) sensitivity to surprisingness increases with age, appearing in our task by age 5. [ABSTRACT FROM AUTHOR]

How does it feel to be curious? We reasoned that there are two sides to curiosity:not knowingsomething (i.e. information-gap) andalmost knowingsomething (i.e. anticipation of resolution). In three experiments, we showed that time affects the relative impact of these two components: When people did not expect to close their information-gap soon (long time-to-resolution) not knowing affected the subjective experience of curiosity more strongly than when they expected to close their information-gap quickly (short time-to-resolution). As such, people experienced less positive affect, more discomfort, and more annoyance with lack of information in a long than a short time-to-resolution situation. Moreover, when time in the long time-to-resolution setting passed, the anticipation of the resolution became stronger, positive affect increased, and discomfort and annoyance with lack of information decreased. Time is thus a key factor in the experience of curiosity. [ABSTRACT FROM AUTHOR]

Second- through fourth-grade students were read a storybook that described a typical boy who interacted with an obese boy for one of four reasons (sympathy, curiosity, teacher instructed, or no reason) to explore the manner in which a typical storybook character's reason for associating with an obese storybook character influences children's responses to both characters. Results revealed that the children responded more favorably to the obese storybook character after than before learning about the typical storybook character's association with him, especially when the typical storybook character's reason for association was presented as internally motivated (sympathy or curiosity). In contrast to “stigma by association” findings reported in prior research, the children also responded more favorably to the typical storybook character after than before his association with the obese storybook character. [ABSTRACT FROM PUBLISHER]

Background:Intellectual curiosity can be defined as a desire for knowledge that leads to exploratory behavior and consists of an inherent and stable trait (i.e. trait curiosity) and a variable context-dependent state (i.e. state curiosity). Although intellectual curiosity has been considered an important aspect of medical education and practice, its relationship to medical education has not been empirically investigated. The purpose of this exploratory study was to describe medical students’ intellectual curiosity across a four-year undergraduate program. Methods:We employed a cross-sectional design in which medical students, across a four-year undergraduate program at McGill University, completed the Melbourne Curiosity Inventory as a measure of their state and trait intellectual curiosity. A Mixed Models ANOVA was used to compare students across year of training. Results:Four hundred and two out of 751 students completed the inventory (53.5%). Trait curiosity was significantly higher than state curiosity (M = 64.5, SD = 8.5 versusM = 58.5, SD = 11.6) overall, and within each year of training. Conclusions:This study is the first to describe state and trait intellectual curiosity in undergraduate medical education. Findings suggest that medical students’ state curiosity may not be optimally supported and highlight avenues for further research. [ABSTRACT FROM PUBLISHER]