Perinatal environmental enrichment changes anxiety-like behaviours in mice and produces similar intergenerational benefits in offspring.

Environmental enrichment implemented in early life is able to induce long-term changes in gene expression, synaptic function and behavioural responses. In this study, we evaluated the adult behavioural effects of perinatal environment enrichment in male and female mice (PEE), as well as the males and females of PEE male offspring (OPEE). For this purpose, animals were submitted to the following battery of behavioural analyses: elevated plus maze, open field test, light-dark box and novelty suppression feeding test. The frontal cortex and ventral hippocampus of PEE mice were collected for the evaluation of the expression of gamma-aminobutyric acid (GABA)-related genes. The PEE animals showed an increase in exploratory activity, associated with a reduction in anxiety-like behaviours on the elevated plus maze; this effect was mainly observed in males. Additionally, the male OPEE showed a reduction in anxiety-like behaviours on the elevated plus maze, mainly observed in a reduction of risk assessment-related behaviours. The PEE male mice also showed reduced expression of Gabra3 in the ventral hippocampus when compared to the control group. These results demonstrate that perinatal environmental enrichment promotes a reduction in anxiety-like behaviour that can be transferred intergenerationally.

Valerenic acid reduces anxiety-like behavior in young adult, female (C57BL/6J) mice.

Extracts from the plant Valeriana officinalis are marketed as an herbal remedy to treat anxiety and insomnia. Valerenic acid (VA) is a major chemical component of Valeriana extracts. To date, there is relatively little information about how VA affects behavior. The purpose of these experiments was to (1) test whether administration of VA induces measurable changes in anxiety-like, depression-like, or locomotor behaviors; (2) determine whether the effects of VA on behavior are dose-dependent; and (3) compare the effects of VA on behavior to those of diazepam, a commonly prescribed treatment for anxiety. Young adult, female mice (C57BL/6J; 3-4 months old; 12 mice/group) were given one of three dosages of VA (3 mg/kg, 6 mg/kg, or 12 mg/kg), diazepam (1 mg/kg), or a vehicle control solution (20% ethanol v/v) by intraperitoneal injection. Thirty minutes after injection, each mouse was tested in the elevated plus maze (EPM), open field test (OFT), and tail suspension test (TST), in that order. All tests were video recorded and analyzed for relevant behavioral parameters. The results demonstrated that VA treatment effectively reduced multiple anxiety-related behaviors measured in the EPM. In fact, at a dose of 12 mg/kg, the anxiolytic effect of VA was just as robust as that of diazepam. Furthermore, the effects of VA on behavior were specifically anxiolytic, as VA did not induce changes in locomotor activity in the OFT, or depression-related behavior as measured in the TST. Our results provide strong support for VA as a putative anxiolytic drug.

Effects of reproductive status on behavioral and neural responses to isolated pup stimuli in female California mice.

The transition to motherhood in mammals is marked by changes in females' perception of and responsiveness to sensory stimuli from infants. Our understanding of maternally induced sensory plasticity relies most heavily on studies in uniparental, promiscuous house mice and rats, which may not be representative of rodent species with different life histories. We exposed biparental, monogamous California mouse (Peromyscus californicus) mothers and ovariectomized virgin females to one of four acoustic and olfactory stimulus combinations (Control: clean cotton and white noise; Call: clean cotton and pup vocalizations; Odor: pup-scented cotton and white noise; Call + Odor: pup-scented cotton and pup vocalizations) and quantified females' behavior and Fos expression in select brain regions. Behavior did not differ between mothers and ovariectomized virgins. Among mothers, however, those exposed to the Control condition took the longest to sniff the odor stimulus, and mothers exposed to the Odor condition were quicker to sniff the odor ball compared to those in the Call condition. Behavior did not differ among ovariectomized virgins exposed to the different conditions. Fos expression differed across conditions only in the anterior hypothalamic nucleus (AHN), which responds to aversive stimuli: among mothers, the Control condition elicited the highest AHN Fos and Call + Odor elicited the lowest. Among ovariectomized virgin females, Call elicited the lowest Fos in the AHN. Thus, reproductive status in California mice alters females' behavioral responses to stimuli from pups, especially odors, and results in the inhibition of defense circuitry in response to pup stimuli.

The Relationship Between Aggression and Physical Disease in Dogs.

Aggression is a very common behavioral problem in dogs. Although aggression can be part of the normal behavior of dogs, medical conditions can either trigger aggression as in the case of intracranial tumors or aggravate an existing aggression problem as it happens with painful conditions. Therefore, it is essential to include an assessment of physical health in the diagnostic protocol of canine aggression.

The Effects of Fitness Training on Working Dog Behavior: Two Case Studies.

Working dogs perform complex tasks that require both physical and behavioral soundness. Two case studies demonstrate how fitness training moderated arousal levels, facilitated training, and improved performance measures in different situations. Fitness training can be beneficial when integrated as part of a working dog's training regimen because it can have a significant influence on their overall health, behavior, and ability to perform their working role effectively.

Cognitive Changes Associated with Aging and Physical Disease in Dogs and Cats.

Behavior changes may indicate primary physical disease or primary behavioral disorders in veterinary patients. It is imperative to recognize that secondary behavioral problems can develop due to medical causes. The incidence of systemic disease increases with age and behavior manifestations can be similar to those expected with cognitive dysfunction syndrome. In this article, we review basic concepts of cognition, aging, and cognitive dysfunction syndrome. Additionally, we provide information regarding factors that influence cognition, and the role medical conditions have on the behavior of aging pets.

Behavior and Cognition of the Senior Cat and Its Interaction with Physical Disease.

In cats, age-related pathologic condition and neurologic degeneration can produce changes in activity, vocalization, appearance, appetite, litter box use, sleep-wake cycle, personality, and cognitive ability. These changes can influence the relationship between owner and pet. Although cognitive dysfunction syndrome (CDS) can cause altered behavior later in life, other medical or behavioral causes may mimic these clinical signs or complicate diagnosis. Management and treatment of CDS can be accomplished through pharmacologic intervention, diet and nutritional supplementation, and environmental enrichment aimed at slowing the progression of the disease.

The effects of valproic acid neurotoxicity on aggressive behavior in zebrafish autism model.

Valproic acid (VPA) is an effective drug, which is preferred for the treatments of epilepsy and various kinds of seizures. Nonetheless, VPA has many side effects associated with autism spectrum disorder (ASD). Therefore, we conducted molecular and behavior tests in adult proactive zebrafish after VPA exposure to investigate gene transcription changes, social behavior, aggression, anxiety and locomotion. Our findings revealed that VPA exposure generates ASD-like phenotypes and behaviors: genes associated with autism, such as adsl, mbd5 and shank3a altered; social interaction deficit. Further behavioral patterns suggest that VPA exposure induces decreases in aggression and increases the anxiety behavior and body cortisol significantly. VPA exposure did not affect locomotor activity in zebrafish. Additionally, we used correlative analyses to investigate the robustness between the ASD-related genes and the different behavior tests, results showed that ASD-related genes are negatively associated with aggressive behavior. Our study demonstrated that aggressive behavior assay is a better predictor of behavior for neurotoxicology of VPA.

Widely targeted metabolomics unveils baicalin-induced hippocampal metabolic alternations in a rat model of chronic unpredictable mild stress.

Baicalin has various neuroprotective effects in models of nervous system disease. Our study has shown baicalin could alleviate depressive-like behaviors in a neuroendocrine mouse model. But the systematic metabolic characteristic and particular targets of baicalin in regulating depressive behaviors have never been investigated. Therefore, this study aims to reveal the hippocampal metabolic profiling of chronic unpredictable mild stress (CUMS) induced depressive rats and the potential metabolic variations after baicalin treatment. We first used the sucrose preference test and open field test to access the antidepressant effects of baicalin. Then, metabolites of the hippocampus after baicalin therapy were monitored by widely-targeted metabolomics based on ultra-performance liquid chromatography-tandem mass spectrometry technology. Finally, the potential mechanism associated with neurogenesis obtained from metabolomics was verified by immunohistochemistry. The results showed that baicalin(40,80 mg/kg) could significantly alleviate depressive behaviors induced by CUMS as demonstrated by an increase in sucrose preference and movement distance and stand-up times in open field test. In the metabolomic analysis, a total of 733 metabolites were identified after baicalin treatment including 15 differential metabolites such as organic acid and its derivatives, heterocyclic compounds, fatty acid, bile acids, amino acid and its metabolites, and so on. Enrichment for differential metabolites showed that the differential metabolites might be involved in the process of folate and cofactor biosynthesis, cholesterol metabolism, primary bile acid biosynthesis, tyrosine metabolism and dopaminergic synapse. Moreover, immunohistochemical analysis confirmed baicalin could facilitate hippocampal neurogenesis of depressive rats in CUMS model. These results suggested baicalin might exert antidepressant effects through regulating the differential metabolites which might play a crucial role in inhibiting oxidative stress and improving neurogenesis. Our findings wish to discover the potential mechanism of baicalin on depression from the metabolomics perspective and promote its clinical application.

"Comparative evaluation of different chemical agents induced Autism Spectrum Disorder in experimental Wistar rats".

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with uncertain etiology and pathophysiology. Several studies revealed that the commonly used animal models like Valproic Acid (VPA) and Propionic Acid (PPA) do not precisely represent the disease as the human patient does. The current study was conducted on different chemically (VPA, PPA, Poly I:C, Dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)) & Chlorpyrifos (CPF)) induced ASD-like animal models and validated the best suitable experimental animal model, which would closely resemble with clinical features of the ASD. This validated model might help to explore the pathophysiology of ASD. This study included rat pups prenatally exposed to VPA, PPA, Poly I:C, Dioxin & CPF within GD9 to GD15 doses. The model groups were validated through developmental and behavioral parameters, Gene Expressions, Oxidative Stress, and Pro-inflammatory and Anti-inflammatory cytokines levels. Developmental and neurobehavioral parameters showed significant changes in model groups compared to the control. In oxidative stress parameters and neuro-inflammatory cytokines levels, model groups exhibited high oxidative stress and neuro-inflammation compared to control groups. Gene expression profile of ASD-related genes showed significant downregulation in model groups compared to the control group. Moreover, the Poly I:C group showed more significant results than other model groups. The comparison of available ASD-like experimental animal models showed that the Poly I:C induced model represented the exact pathophysiology of ASD as the human patient does. Poly I:C was reported in the maternal immune system activation via the inflammatory cytokines pathway, altering embryonic development and causing ASD in neonates.

Cat Inappropriate Elimination and its Interaction with Physical Disease.

Inappropriate elimination or behavioral periuria/perichezia is likely the most reported feline behavioral problem worldwide. A change in behavior is often one of the early signs of physical disease and in addition can aggravate an existing behavioral response. An initial determination of causation is essential; is it medical or behavioral, or a combination of both? Stress activates both the sympathetic adrenomedullary system for short-term responses and the hypothalamic pituitary adrenal axis for long-term responses. Once medical problems have been treated or ruled out, attention should shift to minimizing and using various therapeutic options to help improve and/or resolve undesirable elimination problems.

Hermit crabs as model species for investigating the behavioural responses to pollution.

Human impacts on the environment affect organisms at all levels of biological organisation and ultimately can change their phenotype. Over time, phenotypic change may arise due to selection but individual phenotypes are also subject to change via genotype × environment interactions. In animals, behaviour is the most flexible aspect of phenotype, and hence the most liable to change across environmental gradients including exposure to pollution. Here we review current knowledge on the impacts of pollution, broadly defined to include the release of substances, energy, and the effects of carbon emissions, on the behaviour of a highly studied group, the globally distributed hermit crabs. We first show how their obligate association with empty gastropod shells underpins their use as model organisms for the study of resource-assessment, contest, and risk-coping behaviours. Intense study of hermit crabs has advanced our understanding of how animals use information, and we discuss the ways in which pollutants can disrupt the cognitive processes involved. We then highlight current studies of hermit crabs, which paint a clear picture of behavioural changes due to multiple pollutants. Impacts on behaviour vary across pollutants and entire suites of behaviours can be influenced by a single pollutant, with the potential for interactive and cascade effects. Hermit crabs offer the opportunity for detailed behavioural analysis, including application of the repeated measures animal-personality framework, and they are highly amenable to experimental manipulations. As such, we show how they now provide a model system for studying the impacts of pollution on behaviour, yielding insights broadly applicable across animal diversity.

Digitally-enhanced dog behavioral testing.

Behavioral traits in dogs are assessed for a wide range of purposes such as determining selection for breeding, chance of being adopted or prediction of working aptitude. Most methods for assessing behavioral traits are questionnaire or observation-based, requiring significant amounts of time, effort and expertise. In addition, these methods might be also susceptible to subjectivity and bias, negatively impacting their reliability. In this study, we proposed an automated computational approach that may provide a more objective, robust and resource-efficient alternative to current solutions. Using part of a 'Stranger Test' protocol, we tested n = 53 dogs for their response to the presence and neutral actions of a stranger. Dog coping styles were scored by three dog behavior experts. Moreover, data were collected from their owners/trainers using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ). An unsupervised clustering of the dogs' trajectories revealed two main clusters showing a significant difference in the stranger-directed fear C-BARQ category, as well as a good separation between (sufficiently) relaxed dogs and dogs with excessive behaviors towards strangers based on expert scoring. Based on the clustering, we obtained a machine learning classifier for expert scoring of coping styles towards strangers, which reached an accuracy of 78%. We also obtained a regression model predicting C-BARQ scores with varying performance, the best being Owner-Directed Aggression (with a mean average error of 0.108) and Excitability (with a mean square error of 0.032). This case study demonstrates a novel paradigm of 'machine-based' dog behavioral assessment, highlighting the value and great promise of AI in this context.

Behavioral Characterization of an Angelman Syndrome Mouse Model.

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of AS. We use the rotarod learning paradigm, detailed gait analysis, and nest building test to detect and characterize animal motor impairments. We test animal emotionality in the open field and elevated plus maze tests, as well as the affect in the tail suspension test. When AS mice are tested in the open field test, the results should be interpreted with care, since motor dysfunctions influence mouse behavior in the maze and alter activity scores. The reproducibility and effectiveness of the presented behavioral tests has already been validated in several independent Uba3a mouse lines with different knockout variants, establishing this set of tests as an excellent validation tool in AS research. Models with the relevant construct and face validity will warrant further investigations to elucidate the pathophysiology of the disease and grant the development of causal treatments.

MA-5 ameliorates autism-like behavior in mice prenatally exposed to valproic acid.

Indole-3-acetic acid is a common naturally occurring auxin in plants. A synthesized derivative of this compound, 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid also called mitochonic acid 5 (MA-5), has shown to increase the survival ratio of fibroblasts from patients with mitochondrial disease under stress-induced conditions. Further studies verified its efficacy in pathological models, such as an ischemia-reperfusion model, possibly by increasing ATP production. However, the efficacy of MA-5 in mental disorders, such as anxiety, schizophrenia, and autism spectrum disorders (ASD), has not been investigated. Our study focused on examining the effect of MA-5 in a mouse model of ASD induced by prenatal exposure to valproic acid (VPA). VPA exposure significantly deteriorated the level of anxiety and exploratory behavior in an open field test. We fed mice an MA-5-containing diet for 5 weeks and observed an improvement in the above behavior in the MA-5-fed groups. The efficacy of MA-5 was also observed in the elevated plus maze and three-chambered tests. These findings suggest that MA-5 could potentially be used to treat ASD, especially in patients with mitochondrial dysfunction.

Behavioural issues: castration may not be the solution.

Removing the source of reproductive hormones may not be a panacea for unwelcome or unwanted behaviours - in fact, it may compound them.

X3DFast model for classifying dairy cow behaviors based on a two-pathway architecture.

Behavior is one of the important factors reflecting the health status of dairy cows, and when dairy cows encounter health problems, they exhibit different behavioral characteristics. Therefore, identifying dairy cow behavior not only helps in assessing their physiological health and disease treatment but also improves cow welfare, which is very important for the development of animal husbandry. The method of relying on human eyes to observe the behavior of dairy cows has problems such as high labor costs, high labor intensity, and high fatigue rates. Therefore, it is necessary to explore more effective technical means to identify cow behaviors more quickly and accurately and improve the intelligence level of dairy cow farming. Automatic recognition of dairy cow behavior has become a key technology for diagnosing dairy cow diseases, improving farm economic benefits and reducing animal elimination rates. Recently, deep learning for automated dairy cow behavior identification has become a research focus. However, in complex farming environments, dairy cow behaviors are characterized by multiscale features due to large scenes and long data collection distances. Traditional behavior recognition models cannot accurately recognize similar behavior features of dairy cows, such as those with similar visual characteristics, i.e., standing and walking. The behavior recognition method based on 3D convolution solves the problem of small visual feature differences in behavior recognition. However, due to the large number of model parameters, long inference time, and simple data background, it cannot meet the demand for real-time recognition of dairy cow behaviors in complex breeding environments. To address this, we developed an effective yet lightweight model for fast and accurate dairy cow behavior feature learning from video data. We focused on four common behaviors: standing, walking, lying, and mounting. We recorded videos of dairy cow behaviors at a dairy farm containing over one hundred cows using surveillance cameras. A robust model was built using a complex background dataset. We proposed a two-pathway X3DFast model based on spatiotemporal behavior features. The X3D and fast pathways were laterally connected to integrate spatial and temporal features. The X3D pathway extracted spatial features. The fast pathway with R(2 + 1)D convolution decomposed spatiotemporal features and transferred effective spatial features to the X3D pathway. An action model further enhanced X3D spatial modeling. Experiments showed that X3DFast achieved 98.49% top-1 accuracy, outperforming similar methods in identifying the four behaviors. The method we proposed can effectively identify similar dairy cow behaviors while improving inference speed, providing technical support for subsequent dairy cow behavior recognition and daily behavior statistics.

Embryonic exposure to artificial light at night impairs learning abilities and their covariance with behavioural traits in teleost fish.

The natural light cycle has profound effects on animals' cognitive systems. Its alteration owing to human activities, such as artificial light at night (ALAN), affects the biodiversity of mammalian and avian species by impairing their cognitive functions. The impact of ALAN on cognition, however, has not been investigated in aquatic species, in spite of the common occurrence of this pollution along water bodies. We exposed eggs of a teleost fish (the zebrafish Danio rerio) to ALAN and, upon hatching, we measured larvae' cognitive abilities with a habituation learning paradigm. Both control and ALAN-exposed larvae showed habituation learning, but the latter learned significantly slower, suggesting that under ALAN conditions, fish require many more events to acquire ecologically relevant information. We also found that individuals' learning performance significantly covaried with two behavioural traits in the control zebrafish, but ALAN disrupted one of these relationships. Additionally, ALAN resulted in an average increase in larval activity. Our results showed that both fish's cognitive abilities and related individual differences are negatively impacted by light pollution, even after a short exposure in the embryonic stage.

Early-life maternal deprivation in rats increases sensitivity to the subsequent stressors: a pilot study.

Early life experiences, particularly maternal deprivation (MD), have long-lasting implications on emotional and cognitive development. Using Wistar rats as a model, this study explores the impact of MD followed by predator stress exposure (PSS) to simulate aspects of post-traumatic stress disorder (PTSD). A cohort of 41 male rat pups underwent MD from postnatal days 2 to 14, followed by PSS at day 90. Female rat pups were not included in the experiment. Behavior was subsequently assessed using the Elevated Plus Maze test 14 days post-PSS. While MD led to subtle changes such as decreased activity and increased anxiety-like behavior, PSS induced pronounced anxiogenic effects. Notably, PSS after MD resulted in decreased basal corticosterone levels, mirroring conditions observed in PTSD. The findings suggest that although MD itself does not induce significant behavioral changes, it predisposes individuals to heightened sensitivity to subsequent stressors. This study underscores the utility of a two-stage PSS model for more accurately reflecting the complexities inherent in stress-related disorders, including PTSD.

Play behavior: Tickle and play in the periaqueductal gray.

A new study has identified the periaqueductal gray as an important brain region for play and tickle behavior in rats.