A behavioral analysis system MCFBM enables objective inference of songbirds' attention during social interactions.

Understanding animal behavior is crucial in behavioral neuroscience, aiming to unravel the mechanisms driving these behaviors. A significant milestone in this field is the analysis of behavioral reactions during social interactions. Despite their importance in social learning, the behavioral aspects of these interaction are not well understood in detail due to the lack of appropriate tools. We introduce a high-precision, marker-based motion-capture system for analyzing behavior in songbirds, accurately tracking body location and head direction in multiple freely moving finches during social interaction. Focusing on zebra finches, our analysis revealed variations in eye use based on individuals presented. We also observed behavioral changes during virtual and live presentations and a conditioned-learning paradigm. Additionally, the system effectively analyzed social interactions among mice. This system provides an efficient tool for advanced behavioral analysis in small animals and offers an objective method to infer their focus of attention.

Behavioral and histological analyses of the mouse Bassoon p.P3882A mutation corresponding to the human BSN p.P3866A mutation.

Tauopathy is known to be a major pathognomonic finding in important neurodegenerative diseases such as progressive supranuclear palsy (PSP) and corticobasal degeneration. However, the mechanism by which tauopathy is triggered remains to be elucidated. We previously identified the point mutation c.11596C > G, p.Pro3866Ala in the Bassoon gene (BSN) in a Japanese family with PSP-like syndrome. We showed that mutated BSN may have been involved in its own insolubilization and tau accumulation. Furthermore, BSN mutations have also been related to various neurological diseases. In order to further investigate the pathophysiology of BSN mutation in detail, it is essential to study it in mouse models. We generated a mouse model with the mouse Bassoon p.P3882A mutation, which corresponds to the human BSN p.P3866A mutation, knock-in (KI) and we performed systematic behavioral and histological analyses. Behavioral analyses revealed impaired working memory in a Y-maze test at 3 months of age and decreased locomotor activity in the home cage at 3 and 12 months of age in KI mice compared to those in wild-type mice. Although no obvious structural abnormalities were observed at 3 months of age, immunohistochemical studies showed elevation of Bsn immunoreactivity in the hippocampus and neuronal loss without tau accumulation in the substantia nigra at 12 months of age in KI mice. Although our mice model did not show progressive cognitive dysfunction and locomotor disorder like PSP-like syndrome, dopaminergic neuronal loss was observed in the substantia nigra in 12-month-old KI mice. It is possible that BSN mutation may result in dopaminergic neuronal loss without locomotor symptoms due to the early disease stage. Thus, further clinical course can induce cognitive dysfunction and locomotor symptoms.

Leveraging Zero-Effort Technology for Quantification of Sleep Quality Metrics.

Sleep quality is a critical factor in human health and well-being, with implications for various physiological and psychological processes. Traditional methods of sleep data collection are often limited by the quality and reliability of the data due to issues such as recall bias and subjective interpretation. This research aims to propose a novel framework that objectively measures and evaluates sleep quality using smart thermostats equipped with motion sensors, providing noninvasive and effortless sleep monitoring. The study conducts a comprehensive analysis of sleep patterns, exploring the relationship between activity sensors and sleep quality. By analyzing behavioral characteristics, the study identifies periods or clusters of days that require attention in terms of health and stress levels. The approach ensures privacy, ease of access, and integrates environmental factors, enabling a comprehensive understanding of an individual's sleep health. The findings suggest that this zero-effort technology can significantly enhance sleep monitoring at both individual and population levels, with implications for health monitoring, stress management, and personalized healthcare interventions. Future work will focus on expanding the data set, incorporating more variables, and integrating contextual data to further improve sleep quality analysis and support real-time health interventions.

Dynamic changes in seizure state and anxiety-like behaviors during pentylenetetrazole kindling in rats.

INTRODUCTION: Excessive anxiety is a mental disorder, and its treatment involves the use of benzodiazepines, a class of drugs that enhance the effects of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor. Anxiety disorders are frequent comorbidities in patients with epilepsy, and it has been speculated that anxiety disorders and epileptic seizures share common neurobiological mechanisms. However, conflicting results regarding anxiolytic and anxiogenic effects have been reported in animal models of epilepsy induced by pentylenetetrazole (PTZ) injections, and the causes of this discrepancy are unknown. We hypothesized that anxiety-like behaviors would change dynamically according to the changes in epilepsy susceptibility that occur during the PTZ kindling process. Therefore, we attempted to change anxiety-like behaviors bidirectionally depending on the number of PTZ injections. METHODS: Adult male rats were injected with PTZ 20 times every other day, and stages of seizure onset were classified according to the Racine staging system. Anxiety-like behaviors were measured after 10 and 20 injections. The control group was injected with an equal volume of saline solution. Anxiety-like behaviors were investigated using the open-field, light/dark transition, elevated plus maze, and social interaction tests. RESULTS: Bimodal changes in seizure stage were observed in response to PTZ kindling. The increase in the seizure stage was transiently suppressed after 10 injections, and this decrease in epileptic sensitivity disappeared after 20 injections. However, none of the rats reached a fully kindled state after 20 PTZ injections. After 10 PTZ injections, anxiety-like behaviors decreased compared with those of the control group in the open field, light/dark transition, and elevated plus-maze tests. The anxiolytic effects correlated with the seizure stage in individual rats. After 20 PTZ injections, anxiety-like behaviors returned to control levels. CONCLUSION: PTZ kindling induced bimodal changes in the seizure stage. Anxiety-like behaviors decreased with transient decrease in epileptic sensitivity and returned to control levels with the disappearance of these states. These findings suggest a common neurobiological mechanism underlying anxiety disorders and epileptic seizures. In addition, the discrepancy in the previous studies, in which anxiety levels increase or decrease in PTZ-kindled animals, may be due to examination at different phases of the kindling process.

Comparative Analysis of Gender-Based Differences in Behavioral Mastery, Goals, and Characteristics in Autistic Individuals: An Applied Behavior Analysis Study.

Introduction  It is widely recognized that the prevalence and diagnosis of autism spectrum disorder (ASD) are more common in males than in females. Despite this, there is a significant gap in the body of autism research that investigates gender differences for treatment effects of applied behavior analysis (ABA) across a variety of measured variables. This research aims to comprehensively evaluate gender distinctions concerning target behavioral objectives, goals, and deficit variables. Materials and methods This study analyzed retrospective data from 100 participants, including 89 juveniles and four adults, with seven cases lacking age documentation, who underwent a three-month ABA program from March 19 to June 11, 2023. The ABA program included various methodologies such as functional analysis, discrete trial training, mass trials, and naturalistic training. Data on outcome measures, including target behavioral proficiency, age, average trials to proficiency, average teaching days to proficiency, open behavioral objectives, and target trends, were collected using the "Catalyst" software (Catalyst Software Corporation, New York, NY). Participant demographics were summarized using statistical analyses for categorical (gender and race/ethnicity) and continuous variables (percentage of mastered behavioral objectives, age, average trials, average teaching days, open objectives, percentage of failed objectives during maintenance, percentage of objectives with upward, downward, and flat trends). These statistics included mean, standard deviation, median, and range and were analyzed inferentially using nine separate two-sample independent t-tests and corresponding effect sizes using Cohen's d. Results There were no statistically significant disparities based on gender (p > 0.05) across all nine variables examined: Percentage of Targets Mastered, Age, Average Trials to Mastery, Average Teaching Days to Mastery, Open Targets, Percentage of Targets Failed in Maintenance, Percentage of Targets Trending Up, Percentage of Targets Trending Down, and Percentage of Targets Trending Flat, and wide confidence intervals were detected. Conclusions  Non-significant gender differences in response to ABA treatments regarding these nine behavioral goals, mastery, and deficit variables may be relevant. They suggest that ABA treatments could be equally beneficial for both male and female autistic individuals. These results should be interpreted cautiously. The general pattern observed, characterized by broad confidence intervals, carries a degree of statistical uncertainty, which may suggest substantial gender differences. These results might question the prevailing beliefs about the variation in treatment response based on gender. This could profoundly impact clinical practices, implying that healthcare professionals should not favor one gender over another when suggesting ABA therapies. Instead, the treatment advice should be tailored to each child's unique requirements and traits, regardless of gender. The investigators expect these results to encourage additional research in this field. Comprehending the elements that affect treatment response is vital for improving treatment results and customizing care.

Optimisation of Remote Monitoring Programmes in Heart Failure: Evaluation of Patient Drop-Out Behaviour and Healthcare Professionals' Perspectives.

Heart failure (HF) is a growing epidemic, affecting millions of people worldwide, and is a major cause of mortality, morbidity, and impaired quality of life. Traditional cardiac rehabilitation is a valuable approach to the physical and quality-of-life recovery of patients with cardiovascular disease. The innovative approach of remote monitoring through telemedicine offers a solution based on modern technologies, enabling continuous collection of health data outside the hospital environment. Remote monitoring devices present challenges that could adversely affect patient adherence, resulting in the risk of dropout. By applying a cognitive-behavioral model, we aim to identify the antecedents of dropout behavior among patients adhering to traditional cardiac rehabilitation programs and remote monitoring in order to improve the latter. Our study was conducted from October 2023 to January 2024. In the first stage, we used data from literature consultation. Subsequently, data were collected from the direct experience of 49 health workers related to both remote monitoring and traditional treatment, recruited from the authors' workplace. Results indicate that patients with cardiovascular disease tend to abandon remote monitoring programs more frequently than traditional cardiac rehabilitation therapies. It is critical to design approaches that take these barriers into account to improve adherence and patient satisfaction. This analysis identified specific antecedents to address, helping to improve current monitoring models. This is crucial to promote care continuity and to achieve self-management by patients in the future.

Zebrafishtracker3D: A 3D skeleton tracking algorithm for multiple zebrafish based on particle matching.

Zebrafish are considered as model organisms in biological and medical research because of their high degree of homology with human genes. Automatic behavioral analysis of multiple zebrafish based on visual tracking is expected to improve research efficiency. However, vision-based multi-object tracking algorithms often suffer from data loss owing to mutual occlusion. In addition, simply tracking zebrafish as points is not sufficient-more detailed information, which is required for research on zebrafish behavior. In this paper, we propose Zebrafishtracker3D, which utilizes a skeleton stability strategy to reduce detection error caused by frequent overlapping of multiple zebrafish effectively and estimates zebrafish skeletons using head coordinates in the top view. Further, we transform the front- and top-view matching task into an optimization problem and propose a particle-matching method to perform 3D tracking. The robustness of the algorithm with respect to occlusion is estimated on the dataset comprising two and three zebrafish. Experimental results demonstrate that the proposed algorithm exhibits a multiple object tracking accuracy (MOTA) exceeding 90% in the top view and a 3D tracking matching accuracy exceeding 90% in the complex videos with frequent overlapping. It is noteworthy that each instance in the trace saves its skeleton. In addition, Zebrafishtracker3D is applied in the zebrafish courtship experiment, establishes the stability of the method in applications of life science, and proves that the data can be used for behavioral analysis. Zebrafishtracker3D is the first algorithm that realizes 3D skeleton tracking of multiple zebrafish simultaneously.

Behavioral assessment of soft skill development in a highly structured pre-health biology course for undergraduates.

In this study, we assessed a highly structured, yearlong, case-based course designed for undergraduate pre-health students. We incorporated both content learning assessments and developed a novel method called Multiple Mini Exams for assessing course impact on the development of skills that professional schools often seek in pre-health students, focusing on students' abilities to collaborate with others, display bedside manners, synthesize patient case details, appropriately use scientific and medical language, and effectively attain patients' medical histories. This novel method utilized a rubric based on desired medical student skills to score videotaped behaviors and interactions of students role playing as doctors in a hypothetical patient case study scenario. Overall, our findings demonstrate that a highly structured course, incorporating weekly student performance and presentation of patient cases encompassing history taking, diagnosis, and treatment, can result in content learning, as well as improve desired skills specific for success in medical fields.

Analyzing the Effects of Age, Time of Day, and Experiment on the Basal Locomotor Activity and Light-Off Visual Motor Response Assays in Zebrafish Larvae.

The recent availability of commercial platforms for behavioral analyses in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor responses (VMRs). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood. In this work, we have analyzed the influence of age (5-8 days post-fertilization), time of day (8:00, 10:00, 12:00, 14:00; 16:00, 18:00, and 20:00 h), and experiment (three experiments performed at different days) on BLA and VMR results (4004 analyses for each behavior) in 143 larvae. The results from both behaviors were adjusted to a random-effects linear regression model using generalized least squares (GLSs), including in the model the effect of the three variables, the second-way interactions between them, and the three-way interaction. The results presented in this manuscript show a specific effect of all three intrinsic factors and their interactions on both behaviors, supporting the view that the most stable time period for performing these behavioral assays is from 10:00 am to 04:00 pm, with some differences depending on the age of the larva and the behavioral test.

Replicative Study of the Impacts of Applied Behavior Analysis on Target Behaviors in Individuals With Autism Using Repeated Measures.

Background  The effectiveness of interventions based on applied behavior analysis (ABA) for individuals with autism has been well documented in numerous meta-analyses, systematic reviews, and cost-benefit analyses. However, an observed 'efficacy-effectiveness gap' exists, which can be attributed to various factors. This third replication study, therefore, has significant implications for the field. By assessing the impact of ABA treatment, specifically involving discrete trial training and mass trials, within a naturalistic environment, the study provides valuable insights that can inform and improve the delivery of ABA treatments in real-world settings. Methods  The study was conducted using a repeated measures research design. Retrospective chart review data were collected from 62 individuals with autism, age (M=8.65, SD=4.53), all of whom were level two autistic and required moderate support in communication, socialization, and daily life. These individuals received ABA treatment over five months. The study measured cumulative target behaviors using a repeated measures design, which allowed for the identification of statistically significant differences across 12 time points. This robust methodology ensures the validity and reliability of the study's findings. Results  Mixed repeated measures analysis of variance (ANOVA) indicated statistical significance (sphericity assumed), F(11,495) = 55.432, p < 0.001 (time). Multiple comparisons using bootstrapped paired t-tests showed p < 0.05 on time points 1-8 and non-significance (p > 0.05) on time points 9-12. There was a significant interaction effect (sphericity assumed) with time x (age category), F(44,495) = 2.338, p < 0.001. Interaction contrasts indicated statistically significant differences over time, mainly within the one-year to four-year-old, five to eight-year-old, and most in the nine to 12-year-old age groups. There was some significance within the 13- to 16-year-old age group and no significance within the 17- to 26-year-old age group. Conclusions  Over five months, individuals with autism who underwent ABA treatments demonstrated a statistically significant enhancement in general target behaviors. This finding is crucial as it underscores the effectiveness of ABA treatments in a naturalistic environment. Moreover, the study's discovery of a significant interaction between time and age in these behaviors provides valuable insights into the impact of age on treatment outcomes. Extensive large-N studies of general ABA broad effectiveness and repeated measures designs are lacking and can lead to further research to improve quality and outcomes. These findings contribute to the body of empirical evidence and emphasize the importance of replicative efficacy studies in ensuring the reliability of research findings.

Pharmacological Investigation of Hypoalbuminemia on the Prolonged and Potentiated Action of Midazolam in Rats.

Midazolam (MDZ) is clinically used for its sedative and anticonvulsant properties. However, its prolonged or potentiated effects are sometimes concerning. The main binding protein of MDZ is albumin, and reduced serum albumin levels could lead to MDZ accumulation, thereby potentiating or prolonging its effects. Previous investigations have not thoroughly examined these phenomena from a behavioral pharmacology standpoint. Consequently, this study aimed to evaluate both the prolonged and potentiated effects of MDZ, as well as the effects of serum albumin levels on the action of MDZ in low-albumin rats. Male Wistar rats were classified into control (20% protein diet), low-protein (5% protein), and non-protein groups (0% protein diet) and were fed the protein-controlled diets for 30 d to obtain low-albumin rats. The locomotor activity and muscle relaxant effects of MDZ were evaluated using the rotarod, grip strength, and open-field tests conducted 10, 60, and 120 min after MDZ administration. Serum albumin levels decreased significantly in the low-protein and non-protein diet groups compared with those in the control group. Compared with the control rats, low-albumin rats demonstrated a significantly shorter time to fall, decreased muscle strength, and a significant decrease in the distance traveled after MDZ administration in the rotarod, grip strength, and open-field tests, respectively. Decreased serum albumin levels potentiated and prolonged the effects of MDZ. Hence, serum albumin level is a critical parameter associated with MDZ administration, which should be monitored, and any side effects related to decreased albumin levels should be investigated.

Effects of hypoxic compound exercise to promote HIF-1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila.

Alteration of HIF-1α expression levels under hypoxic conditions affects the sequence of its downstream target genes thereby producing different effects. In order to investigate whether the effect of hypoxic compound exercise (HE) on HIF-1α expression alters cardiac pumping function, myocardial structure, and exercise capacity, we developed a suitable model of hypoxic exercise using Drosophila, a model organism, and additionally investigated the effect of hypoxic compound exercise on nocturnal sleep and activity behavior. The results showed that hypoxic compound exercise at 6% oxygen concentration for five consecutive days, lasting 1 h per day, significantly improved the cardiac stress resistance of Drosophila. The hypoxic complex exercise promoted the whole-body HIF-1α expression in Drosophila, and improved the jumping ability, climbing ability, moving speed, and moving distance. The expression of HIF-1α in the heart was increased after hypoxic exercise, which made a closer arrangement of myofilaments, an increase in the diameter of cardiac tubules, and an increase in the pumping function of the heart. The hypoxic compound exercise improved the sleep quality of Drosophila by increasing its nocturnal sleep time, the number of deep sleeps, and decreasing its nocturnal awakenings and activities. Therefore, we conclude that hypoxic compound exercise promoted the expression of HIF-1α to enhance the exercise capacity and heart pumping function of Drosophila, and improved the quality of sleep.

Symptom-specific improvement across therapies and their putative mediators: A mediation network intervention analysis.

OBJECTIVE: We evaluated differential treatment effects on specific symptoms and their mediators for Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Supportive Psychotherapy (SP) in persistently depressed patients. METHOD: We conducted a Bayesian mediation network intervention analysis with data from a randomized controlled trial comparing CBASP and SP. Three networks were calculated to investigate (1) differential treatment effects on specific symptoms, (2) differential treatment effects on the potential mediators interpersonal problems and social functioning, and (3) associations between change in symptoms and change in the potential mediators. RESULTS: First, we found no evidence that CBASP more strongly improves most depressive symptoms specifically, except minimal evidence of symptom-specific effects on sleeping problems and self-esteem. Second, no and minimal evidence for differential treatment effects on interpersonal problems and social functioning was shown, respectively. Third, interpersonal problems and social functioning were strongly related to depressive symptoms. CONCLUSION: While CBASP showed superior treatment effects for overall symptom severity, this treatment might not be superior in improving specific symptoms and the potential mediators interpersonal problems and social functioning. Still, interpersonal problems and social functioning seem to play an important role for depression symptoms. Future research needs to further investigate potential working mechanisms of CBASP.Trial registration: ClinicalTrials.gov identifier: NCT00970437.

Behavioral and transcriptomic analyses of mecp2 function in zebrafish.

Rett syndrome (RTT), a human neurodevelopmental disorder characterized by severe cognitive and motor impairments, is caused by dysfunction of the conserved transcriptional regulator Methyl-CpG-binding protein 2 (MECP2). Genetic analyses in mouse Mecp2 mutants, which exhibit key features of human RTT, have been essential for deciphering the mechanisms of MeCP2 function; nonetheless, our understanding of these complex mechanisms is incomplete. Zebrafish mecp2 mutants exhibit mild behavioral deficits but have not been analyzed in depth. Here, we combine transcriptomic and behavioral assays to assess baseline and stimulus-evoked motor responses and sensory filtering in zebrafish mecp2 mutants from 5 to 7 days post-fertilization (dpf). We show that zebrafish mecp2 function is required for normal thigmotaxis but is dispensable for gross movement, acoustic startle response, and sensory filtering (habituation and sensorimotor gating), and reveal a previously unknown role for mecp2 in behavioral responses to visual stimuli. RNA-seq analysis identified a large gene set that requires mecp2 function for correct transcription at 4 dpf, and pathway analysis revealed several pathways that require MeCP2 function in both zebrafish and mammals. These findings show that MeCP2's function as a transcriptional regulator is conserved across vertebrates and supports using zebrafish to complement mouse modeling in elucidating these conserved mechanisms.

Predicting Behavioral Target Mastery With Age, Intensity and Duration, Open Targets, and Maintenance Failure With Applied Behavior Analysis in Individuals With Autism.

Background Researchers have studied the effects of age, treatment intensity, and treatment duration with applied behavior analysis (ABA) outcomes in autistic individuals. This study's primary objective was to evaluate the predictive capabilities of age, intensity, and duration of treatment, open behavioral targets, and behavior maintenance failure on behavioral target mastery. Methods A retrospective cohort of 100 autistic individuals treated with ABA with functional analysis and discrete trial training, mass trials, and naturalistic training were treated and analyzed. Target behavioral mastery data was collected via a retrospective chart review contained within the "Catalyst" tracking software. ABA treatment was administered for three months between March 19, 2023, and June 11, 2023. Multiple linear regression was performed using the percentage of behavioral targets mastered as the dependent variable. The independent variables were age, average trials to behavioral mastery, average teaching days to behavioral mastery, and percentage of behavioral targets that failed in maintenance. Results The multiple linear regression model was statistically significant (R=0.443, R²=0.196, adjusted R2=0.150, F(5, 87)=4.239, p=0.002). The average teaching days to mastery (ß=0.416, p=0.019) and percentage of targets failed in maintenance (ß=0.201, p=0.047) significantly predicted the percentage of behavioral targets mastered. However, age (ß=0.079, p=0.419), average trials to mastery (ß=-0.271, p=0.114), and open targets (ß=0.184, p=0.081) did not significantly predict the percentage of behavioral targets mastered. The analysis of variance (ANOVA) resulted in non-significant (p>0.05) age group differences between the above variables. Conclusions The predictor variables average teaching days to mastery (intensity and duration) and percentage of targets failed in maintenance had a statistically significant effect on the percentage of behavioral targets mastered. The predictor variables age, average trials to behavioral mastery (intensity and duration), and open behavioral targets had a non-significant influence on the percentage of behavioral targets mastered. A non-significant difference between age groups was found in all study variables.

Exploring the Association Between Textual Parameters and Psychological and Cognitive Factors.

Background: Textual data analysis has become a popular method for examining complex human behavior in various fields, including psychology, psychiatry, sociology, computer science, data mining, forensic sciences, and communication studies. However, identifying the most relevant textual parameters for analyzing complex behavior is still a challenge. Goal of Study: This paper aims to explore potential textual parameters that could be useful in analyzing behavior through complex textual data. Furthermore, we have examined the randomly generated text based on different textual parameters. Methods: To achieve this goal, we conducted a comprehensive review of the literature on textual data analysis and identified several potential topics that could be relevant, such as sentiment analysis, discourse analysis, lexical analysis, and syntactic analysis. We discuss the theoretical background and practical implications of each parameter and provide examples of how they have been used in previous research. Furthermore, we highlight the importance of considering the context in which these parameters are applied and the need for interdisciplinary collaboration to gain a deeper understanding of complex behavior through textual data analysis. Furthermore, we have provided Python code in the Supplementary Materials to facilitate a comprehensive analysis of such behaviors. In addition, to generate the text for analysis, we utilized ChatGPT 3.5 Turbo by requesting it to generate a random text of 1000 words divided into five paragraphs. Afterwards, we applied the provided Python code to analyze the randomly generated text. Conclusion: Overall, this paper provides a foundation for researchers to identify relevant textual parameters to analyze complex human behavior in their respective fields such as linguistics, sociology, psychiatry, and psychology.

Mutation of novel ethanol-responsive lncRNA Gm41261 impacts ethanol-related behavioral responses in mice.

Chronic alcohol exposure results in widespread dysregulation of gene expression that contributes to the pathogenesis of Alcohol Use Disorder (AUD). Long noncoding RNAs are key regulators of the transcriptome that we hypothesize coordinate alcohol-induced transcriptome dysregulation and contribute to AUD. Based on RNA-Sequencing data of human prefrontal cortex, basolateral amygdala and nucleus accumbens of AUD versus non-AUD brain, the human LINC01265 and its predicted murine homolog Gm41261 (i.e., TX2) were selected for functional interrogation. We tested the hypothesis that TX2 contributes to ethanol drinking and behavioral responses to ethanol. CRISPR/Cas9 mutagenesis was used to create a TX2 mutant mouse line in which 306 base-pairs were deleted from the locus. RNA analysis revealed that an abnormal TX2 transcript was produced at an unchanged level in mutant animals. Behaviorally, mutant mice had reduced ethanol, gaboxadol and zolpidem-induced loss of the righting response and reduced tolerance to ethanol in both sexes. In addition, a male-specific reduction in two-bottle choice every-other-day ethanol drinking was observed. Male TX2 mutants exhibited evidence of enhanced GABA release and altered GABAA receptor subunit composition in neurons of the nucleus accumbens shell. In C57BL6/J mice, TX2 within the cortex was cytoplasmic and largely present in Rbfox3+ neurons and IBA1+ microglia, but not in Olig2+ oligodendrocytes or in the majority of GFAP+ astrocytes. These data support the hypothesis that TX2 mutagenesis and dysregulation impacts ethanol drinking behavior and ethanol-induced behavioral responses in mice, likely through alterations in the GABAergic system.

Characterizing the dynamic learning process: Implications of a quantitative analysis.

Understanding the neural mechanisms involved in learning processes is crucial for unraveling the complexities of behavior and cognition. Sudden change from the untrained level to the fully-learned level is a pivotal feature of instrumental learning. However, the concept of change point and suitable methods to conveniently analyze the characteristics of sudden change in groups remain elusive, which might hinder a fuller understanding of the neural mechanism underlying dynamic leaning process. In the current study, we investigated the learning processes of mice that were trained in an aversive instrumental learning task, and introduced a novel strategy to analyze behavioral variations in instrumental learning, leading to improved clarity on the concept of sudden change and enabling comprehensive group analysis. By applying this novel strategy, we examined the effects of cocaine and a cannabinoid receptor agonist on instrumental learning. Intriguingly, our analysis revealed significant differences in timing and occurrence of sudden changes that were previously overlooked using traditional analysis. Overall, our research advances understanding of behavioral variation during instrumental learning and the interplay between learning behaviors and neurotransmitter systems, contributing to a deeper comprehension of learning processes and informing future investigations and therapeutic interventions.

A study on the possible neurotoxic effects of CUMYL-4CN-BINACA in Sprague Dawley rats.

Substances such as Δ9-tetrahydrocannabinol (THC) and cannabidiol cross the blood-brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CN-BINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.

An automated group-housed oral fentanyl self-administration method in mice.

RATIONALE AND OBJECTIVES: Social factors play a critical role in human drug addiction, and humans often consume drugs together with their peers. In contrast, in traditional animal models of addiction, rodents consume or self-administer the drug in their homecage or operant self-administration chambers while isolated from their peers. Here, we describe HOMECAGE ("Home-cage Observation and Measurement for Experimental Control and Analysis in a Group-housed Environment"), a translationally relevant method for studying oral opioid self-administration in mice. This setting reduces experimental confounds introduced by social isolation or interaction with the experimenter. METHODS: We have developed HOMECAGE, a method in which mice are group-housed and individually monitored for their consumption of a drug vs. a reference liquid. RESULTS: Mice in HOMECAGE preserve naturalistic aspects of behavior, including social interactions and circadian activity. The mice showed a preference for fentanyl and escalated their fentanyl intake over time. Mice preferred to consume fentanyl in bouts during the dark cycle. Mice entrained to the reinforcement schedule of the task, optimizing their pokes to obtain fentanyl rewards, and maintained responding for fentanyl under a progressive ratio schedule. HOMECAGE also enabled the detection of cage-specific and individual-specific behavior patterns and allowed the identification of differences in fentanyl consumption between co-housed control and experimental mice. CONCLUSIONS: HOMECAGE serves as a valuable procedure for translationally relevant studies on oral opioid intake under conditions that more closely mimic the human condition. The method enables naturalistic investigation of factors contributing to opioid addiction-related behaviors and can be used to identify novel treatments.