Biology subjects

Toda, K.

Publications and source records attributed to Toda, K..

16 recordsLinked to original sources

bioRxiv2026

Social behaviours predict vocal turn-taking in common marmosets

Human conversation depends on the continuous integration of vocal exchanges with visual and spatial cues, yet the evolutionary origins of this multimodal coordination remain poorly understood. Although vocal turn-taking has been documented across many animal species, studies have largely examined vocal exchanges in isolation from the accompanying social dynamics. Using acoustic localization and 3D pose tracking in freely interacting marmoset pairs, we simultaneously quantified vocal behaviour and social interactions during natural communication. We found that vocal turn-taking is dependent on distinct multimodal behavioural states defined by head orientation, spatial proximity, and ongoing social interaction. While call features did not reliably predict turn-taking, these behavioural dynamics predicted whether vocal exchanges developed into turn-taking or terminated after isolated calls. Our findings reveal that primate vocal communication is fundamentally organized by multimodal behavioural coordination rather than by vocal signals alone, providing an evolutionary framework for understanding the origins of human conversation.

neuroscience↗

bioRxiv2026

Multidimensional characterization of the physiological and behavioral effects of TCB-2 in mice

Background and PurposeSerotonergic psychedelics affect behavior and physiology, but the relationships among these effects remain poorly understood. In rodents, the head-twitch response is used as a measure of psychedelic-like activity, yet it does not capture changes in physiological state or the performance of learned behaviors. Here, we investigated the acute effects of the 5-HT2A receptor agonist TCB-2 across several behavioral and physiological measures and examined how these effects were modified by pretreatment with the 5-HT2A receptor antagonist volinanserin. Experimental ApproachMice were tested in head-fixed and freely moving conditions. During a learned auditory trace-conditioning task, we measured licking, pupil area, eye position, and blinking. We measured locomotor activity in an open field and quantified head-twitch responses using a DeepLabCut-based method. To examine the contribution of 5-HT2A receptors, mice were pretreated with the 5-HT2A receptor antagonist volinanserin. Key ResultsTCB-2 caused pupil constriction without detectable changes in eye position or blinking when administered alone. TCB-2 also reduced licking at the highest dose, but the cue-locked temporal pattern of licking remained evident. In freely moving mice, TCB-2 reduced locomotor activity and produced a dose-dependent increase in head-twitch responses. Volinanserin partially attenuated TCB-2-induced pupil constriction and reduced head-twitch responses under some conditions, but it did not consistently prevent the other effects of TCB-2. Conclusions and ImplicationsTCB-2 produced distinct effects across physiological and behavioral measures rather than a uniform disruption of behavioral function. Pronounced pupil constriction and head-twitch responses occurred without detectable changes in eye position or blinking, while the temporal organization of conditioned licking was retained despite a reduction in its magnitude. The incomplete and variable effects of volinanserin preclude definitive conclusions about the receptor mechanisms underlying each response. Combining automated head-twitch detection with physiological and task-related measurements provides a broader framework for comparing the pharmacological profiles of serotonergic compounds. What is already knownO_LIClassical psychedelics produce characteristic effects primarily through serotonin 5-HT2A receptor activation. C_LIO_LIHead-twitch responses capture only one dimension of psychedelic-like drug action. C_LI What this study addsO_LITCB-2 reduced locomotion and licking while preserving the cue-locked pattern of conditioned licking. C_LIO_LIPupil constriction occurred without detectable changes in eye position or blinking. C_LI Clinical significanceO_LIMultidimensional phenotyping can distinguish the physiological and behavioral profiles of serotonergic compounds. C_LIO_LIComplementary measures may improve preclinical evaluation of emerging serotonergic therapeutics. C_LI

pharmacology and toxicology↗

bioRxiv2026

Systemic injection of metabotropic glutamate 2/3 receptor antagonist LY341495 disrupts reward-related behaviors in mice.

Metabotropic glutamate 2/3 receptors (mGluR2/3) have been implicated in depression, anxiety, learning, and memory, yet their role in reward-related behavior remains poorly understood. Here, we examined the effects of the selective mGluR2/3 antagonist LY341495 on reward-related behaviors in mice using a combination of head-fixed and freely moving behavioral paradigms. In a head-fixed temporal conditioning task, mice developed anticipatory licking and pupil dilation preceding the delivery of a 10% sucrose solution, indicating successful temporal anticipation of reward. Systemic administration of LY341495 dose-dependently reduced both anticipatory and consummatory licking. Normalization analyses further suggested that LY341495 reduced the overall expression of licking behavior while largely preserving its temporal organization. LY341495 also induced pupil dilation and attenuated reward-proximity-related pupillary modulation. To determine whether these effects reflected non-specific motor impairments, we assessed locomotor activity in an open-field task and measured ultrasonic vocalizations (USVs) during courtship interaction. LY341495 did not significantly alter locomotion, excretion, or USV production, suggesting preserved general motor and orofacial motor function. In contrast, LY341495 dose-dependently reduced food intake and decreased social preference, indicating that the effects of mGluR2/3 antagonism extend beyond ingestive behavior to social reward-related processes. These findings demonstrate that mGluR2/3 signaling contributes to the regulation of reward-related behaviors across multiple reward domains independently of general motor dysfunction. These results provide new insight into glutamatergic mechanisms underlying motivation and reward processing and may have implications for neuropsychiatric disorders characterized by anhedonia and motivational deficits.

neuroscience↗

bioRxiv2026

Lipopolysaccharide-induced systemic inflammation alters courtship ultrasonic vocalizations in male mice.

BackgroundSickness behavior comprises a coordinated constellation of motivational, cognitive, and social alterations that emerge during systemic inflammation. Although reductions in locomotion, feeding, and social engagement have been extensively characterized, how inflammation affects ultrasonic vocal communication--an ethologically relevant index of social motivation in rodents--remains insufficiently understood. Here, we investigated how systemic immune activation alters male-female social communication in mice by jointly assessing ultrasonic vocalizations (USVs) and approach behavior. MethodsSexually experienced male mice received an intraperitoneal injection of lipopolysaccharide (LPS), and their interactions with a novel estrous female were evaluated 24 h later by quantifying USVs and approach behavior. ResultsLPS administration robustly suppressed both the total number of USVs and the duration of male approach behavior, indicating a pronounced reduction in social motivation. Beyond this quantitative suppression, LPS also induced qualitative changes in vocal output, including shifts in the proportional use of specific USV subtypes and alterations in acoustic features such as sound pressure. ConclusionsThese findings demonstrate that USVs capture multiple dimensions of inflammation-induced disruption of social communication, reflecting not only diminished motivation to engage socially but also changes in the structure of communicative signals themselves. By revealing that systemic immune activation reshapes both social approach behavior and vocal communication patterns, this study establishes USV analysis as a sensitive and translationally relevant behavioral readout for probing neuroimmune mechanisms underlying the social and communicative disturbances characteristic of sickness behavior. More broadly, our results highlight the utility of vocal communication analyses for elucidating how inflammatory processes perturb social circuits and communicative function in health and disease.

animal behavior and cognition↗

bioRxiv2025

Rank-biased access to females in periovulatory periods but comparable copulation rates across ranks in male bonobos at Wamba

ObjectivesFemale bonobos (Pan paniscus) show prolonged sexual swelling and copulate across an unusually extended timeframe, including the postpartum infertile stage. We tested the updated prolonged sexual receptivity hypothesis that the simultaneous presence of multiple receptive females disperses male mating effort and weakens male-male contest competition by examining rank effects on copulation rates and mating partners. Materials and MethodsIn a free-ranging bonobo group at Wamba, we collected copulation and party-composition data using all-day focal follows. Based on daily swelling scores, we operationally defined a likely fertile period (LFP) from detumescence at the end of the maximal swelling phase. We analyzed rank-dependent patterns in copulation rates and mating partners were analyzed using generalized linear mixed models (GLMMs). ResultsCopulation rates did not differ detectably across male dominance ranks, with approximately twice per day on average. In contrast, higher-ranking males were more likely to copulate with LFP females. At the party level, lower-ranking males increasingly copulated with non-LFP females as the number of LFP females present increased. DiscussionThese findings indicate that pronounced male reproductive skew in bonobos appears to arise through rank-biased access to females in the fertile window despite broadly similar copulation rates across males. Subordinate males tendency to shift mating effort toward non-LFP females when LFP females are available may reduce injury risks of direct contest competition while facilitating dominant males to guard fertile females effectively. Therefore, prolonged sexual receptivity in female bonobos could be a key factor yielding the condition where lower male aggression and higher reproductive skew coexist.

animal behavior and cognition↗

bioRxiv2024

Systemic injection of scopolamine increased the variability of temporal prediction in head-fixed mice.

Several theories propose that interval timing and memory share common cognitive mechanisms. Pharmacological disruption of the cholinergic system using scopolamine, a muscarinic acetylcholine receptor antagonist, is widely used as a model of cognitive impairment. However, its effects on temporal prediction remain poorly understood. Previous timing studies in freely moving animals are difficult to interpret because motor activity may confound measures of interval timing. Here, we investigated the effects of systemic scopolamine administration on temporal prediction in mice using a head-fixed behavioral paradigm. Mice were trained on a fixed-time schedule task using a peak procedure, in which a 10% sucrose solution was delivered every 10 s through a spout positioned within licking distance. After training, mice developed anticipatory licking responses that peaked around the expected reward time, demonstrating temporal prediction of reward delivery. Systemic administration of scopolamine increased the variability of temporal prediction in a dose-dependent manner without altering the mean peak time. Trial-by-trial analysis further revealed that scopolamine reduced the duration of licking bouts while preserving the total number of licks during peak trials, suggesting impaired maintenance of reward-directed licking behavior rather than altered reward consumption. In a separate open-field assay, scopolamine increased spontaneous locomotor activity and reduced fecal output. These findings demonstrate that cholinergic blockade disrupts the precision of temporal prediction and alters behavioral organization in mice. The increased variability in timing behavior following scopolamine administration may reflect impaired regulation of transitions between behavioral states, providing new insights into the role of cholinergic signaling in temporal cognition.

neuroscience↗

bioRxiv2024

Extinction burst could be explained by curiosity-driven reinforcement learning

Curiosity encourages agents to explore their environment, leading to learning opportunities. Although psychology and neurobiology have tackled how external rewards control behavior, how intrinsic factors control behavior remains unclear. An extinction burst is a behavioral phenomenon in which a sudden increase in the frequency of a behavior immediately follows the omission of a reward. Although the extinction burst is textbook knowledge in psychology, there is little empirical evidence of it in experimental situations. In this study, we show that the extinction burst can be explained by curiosity by combining computational modeling of behavior and empirical demonstrations in mice. First, we built a reinforcement learning model incorporating curiosity, defined as expected reward prediction errors, and the model additively controlled the agents behavior to the primary reward. Simulations revealed that the curiosity-driven reinforcement learning model produced an extinction burst and burst intensity depended on the reward probability. Second, we established a behavioral procedure that captured extinction bursts in an experimental setup using mice. We conducted an operant conditioning task with head-fixed mice, in which the reward followed after pressing a lever at a given probability. After the training sessions, we occasionally withheld the reward delivery when the mice performed the task. We found that phasic bursts of responses occurred immediately after reward omission when responses were rewarded with a high probability, suggesting that the magnitude of reward prediction errors controlled the burst. These results provide theoretical and experimental evidence that intrinsic factors control behavior in adapting to an ever-changing environment. Significance statementIn theories of learning and behavior, primary rewards such as food, water, and sex occupy a dominant position as factors controlling behavior. However, primary rewards are scarce. Experimental investigations in psychology, neuroscience, ethology, and economics have revealed that novelty, uncertainty, and unpredictability drive behavior. How these intrinsic factors affect behavior is essential for a comprehensive understanding of the principles of learning and behavior. This study provides theoretical and experimental evidence that operant responses in mice are directly controlled by external rewards and intrinsic factors such as curiosity. Our study provides a robust example of curiosity-driven behavior and paves the way for understanding the mechanism of curiosity.

animal behavior and cognition↗

bioRxiv2024

Disruption of ultrasonic vocalization with systemic administration of the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 in adult male mice

Objective: Social behavior and communication, including ultrasonic vocalizations (USVs), are important for survival and reproductive success across species. N-methyl-D-aspartate (NMDA) receptors contribute to the neural mechanisms underlying social behavior, and pharmacological modulation of these receptors can alter both social behavior and USVs in rodents. However, the effects of NMDA receptor blockade on dyadic USVs and social approach during male-female interactions in mice remain incompletely understood. We therefore investigated the effects of systemic administration of MK-801, a noncompetitive NMDA receptor antagonist, on dyadic vocal activity, social approach, locomotor behavior, and excretory outcomes in adult male mice. Methods: Sexually experienced male mice were tested in male-female interaction and same-sex social-preference tasks. Using VocalMat, a machine-learning-based tool, we classified the USVs recorded during male-female interactions into 11 call categories and examined their temporal relationship to the proximity of the male subject to the female stimulus. Results: Administration of MK-801 to the male dose-dependently reduced the total number of USVs recorded from the male-female dyad, with a marked reduction at the highest dose, while leaving the treated male's proximity to the female stimulus unchanged. In the same-sex social-preference task, MK-801 reduced the time spent near the social stimulus at the highest dose, although preference for the social stimulus over the non-social object remained significant under all treatment conditions. MK-801 also increased locomotor activity and reduced fecal output and estimated urine output in the open-field task. These findings demonstrate that systemic NMDA receptor blockade differentially affects dyadic vocal communication, social approach, locomotor activity, and excretory outcomes. Conclusion: Systemic MK-801 administration to the male reduced the number of USVs recorded during male-female interactions and produced distinct effects on social approach, locomotor activity, and excretory outcomes. These findings indicate that NMDA receptor blockade differentially affects multiple behavioral domains, although the mechanisms underlying the reduction in USVs remain to be determined.

pharmacology and toxicology↗

bioRxiv2023

Cold-induced muscle atrophy in zebrafish: insights from swimming activity and gene expression analysis

The investigation into the effects of cold acclimation on fish skeletal muscle function and its potential implications for muscle atrophy is of great interest to us. This study examines how rearing zebrafish at low temperatures affects their locomotor activity and the expression of genes associated with muscle atrophy. Zebrafish were exposed to temperatures ranging from 10 {degrees}C to 25 {degrees}C, and their swimming distance was measured. The expression levels of important muscle atrophy genes, Atrogin-1 and MuRF1, were also evaluated. Our findings show that swimming activity significantly decreases when the water temperature ranges from 10 {degrees}C to 15 {degrees}C, indicating a decrease in voluntary movement. Additionally, gene expression analysis shows a significant increase in the expression of Atrogin-1 and MuRF1 at 10 {degrees}C. This up-regulation could lead to muscle atrophy caused by decreased activity in cold temperatures. To investigate the effects of exercise on reducing muscle atrophy, we subjected zebrafish to forced swimming at a temperature of 8 {degrees}C for ten days. This treatment significantly reduced the expression of Atrogin-1 and MuRF1, emphasizing the importance of muscle stimulation in preventing muscle atrophy in zebrafish. These findings suggest that zebrafish can serve as a valuable model organism for studying muscle atrophy and can be utilized in drug screening for muscle atrophy-related disorders. Cold-reared zebrafish provide a practical and ethical approach to inducing disuse muscle atrophy, providing valuable insights into potential therapeutic strategies for addressing skeletal muscle atrophy.

physiology↗

bioRxiv2023

Label-free ghost cytometry for manufacturing of cell therapy products

Automation and quality control (QC) are critical in manufacturing safe and effective cell and gene therapy products. However, current QC methods, reliant on molecular staining, pose difficulty in in-line testing and can increase manufacturing costs. Here we demonstrate the potential of using label-free ghost cytometry (LF-GC), a machine learning-driven, multidimensional, high-content, and high-throughput flow cytometry approach, in various stages of the cell therapy manufacturing processes. LF-GC accurately quantified cell count and viability of human peripheral blood mononuclear cells (PBMCs) and identified non-apoptotic live cells and early apoptotic/dead cells in PBMCs, T cells and non-T cells in white blood cells (WBCs), activated T cells and quiescent T cells in PBMCs, and particulate impurities in PBMCs. The data support that LF-GC is a non-destructive label-free cell analytical method that can be used to monitor cell numbers, assess viability, identify specific cell subsets or phenotypic states, and remove impurities during cell therapy manufacturing. Thus, LF-GC holds the potential to enable full automation in the manufacturing of cell therapy products with reduced cost and increased efficiency.

cell biology↗

bioRxiv2023

Laser-induced auditory perception: transtympanic laser irradiation of the cochlea from the outer ear evokes an auditory-related neural and behavioral response

Brain-machine interfaces are emerging devices that act as a medium for communication between the neural system and external software and hardware. Over the last decade, there has been a discussion on applying infrared laser stimulation to the brain-machine interfaces, including cochlear implants. Infrared lasers can selectively activate neural populations without introducing exogenous agents to tissues. This study presents the first demonstration that laser irradiation of the cochlea, a peripheral sensory organ, can elicit a clear behavioral auditory response. Mongolian gerbils (Meriones unguiculatus) were divided into two groups, each subjected to classical conditioning where a reward water delivery was predicted by either cochlear laser stimulation or sound stimulus. Laser-conditioned animals successfully learned licking behavior, with conditioned responses and behavioral properties comparable to auditory-conditioned animals. The laser-evoked response was significantly inhibited by auditory masking, and auditory-conditioned animals demonstrated stimulus generalization to laser stimulation. In a subsequent experiment, simultaneous presentation of auditory and laser stimulation induced nonlinear amplification in both auditory cortical and behavioral responses, suggesting that combining auditory and laser stimulation can enhance auditory perception beyond the effects of each stimulus alone. These findings indicate that infrared laser irradiation of the cochlea can potentially evoke and enhance auditory perception, making it a promising candidate for implementation in auditory prostheses.

neuroscience↗

bioRxiv2022

Safety margin evaluations for transtympanic laser stimulation of the cochlea from the outer ear in Mongolian gerbils (Meriones unguiculatus)

Infrared laser cochlear stimulation has been suggested as an alternative to traditional auditory prostheses. Previous research has mainly examined the short-term effects of laser stimulation, but to effectively use this technique, it is necessary to study whether prolonged laser exposure can safely and sustainably induce cochlear responses. This study assessed the effect of laser-induced cochlear damage using classically-conditioned Mongolian gerbils. The white noise was presented as a conditioned stimulus, and reward licking was recorded as a conditioned response. After training, the subjects cochlea was exposed to a continuous pulsed laser for 15 h. The licking rate drastically decreased after the exposure of 26.4 W/cm2, while it did not change after 6.6 W/cm2 or weaker. These findings showed, for the first time, that the safety margin of long-term, at least several hours, cochlear laser stimulation exists and will contribute to the safe and effective delimitation of laser parameters in future research.

bioengineering↗

bioRxiv2022

Pupillary Dynamics of Mice Performing a Pavlovian Delay Conditioning Task Reflect Reward Predictive Signals.

Pupils can signify various internal processes and states, such as attention, arousal, and working memory. Changes in pupil size have been associated with learning speed, prediction of future events, and deviations from the prediction in human studies. However, the detailed relationships between pupil size changes and prediction are unclear. We explored pupil size dynamics in mice performing a Pavlovian delay conditioning task. A head-fixed experimental setup combined with deep-learning-based image analysis enabled us to reduce spontaneous locomotor activity and to track the precise dynamics of pupil size of behaving mice. By setting up two experimental groups, one for which mice were able to predict reward in the Pavlovian delay conditioning task and the other for which mice were not, we demonstrated that the pupil size of mice is modulated by reward prediction and consumption, as well as body movements, but not by unpredicted reward delivery. Furthermore, we clarified that pupil size is still modulated by reward prediction even after the disruption of body movements by intraperitoneal injection of haloperidol, a dopamine D2 receptor antagonist. These results suggest that changes in pupil size reflect reward prediction signals. Thus, we provide important evidence to reconsider the neuronal circuit involved in computing reward prediction error. This integrative approach of behavioral analysis, image analysis, pupillometry, and pharmacological manipulation will pave the way for understanding the psychological and neurobiological mechanisms of reward prediction and the prediction errors essential to learning and behavior. Manuscript contributions to the fieldPredicting upcoming events is essential for the survival of many animals, including humans. Accumulating evidence suggests that pupillary responses reflect autonomic activity and are modulated by noradrenergic, cholinergic, and serotonergic neurotransmission. However, the relationships between pupillary responses, reward prediction, and reward prediction errors remain unclear. This study examined changes in pupil size while water-deprived mice performed a Pavlovian delay conditioning task using a head-fixed setup. The head-fixed experimental setup, combined with deep-learning-based image analysis, enabled us to reduce spontaneous locomotor activity and to track the precise dynamics of the licking response and the pupil size of behaving mice. A well-controlled, rigid behavioral experimental design allowed us to investigate the modulation of behavioral states induced by reward prediction. While pharmacological manipulation might affect pupil size, the combined approach of pupillometry and pharmacological manipulation allowed us to differentiate reward prediction signals and signals modulated by body movements. We revealed that the changes in pupil size (1) reflect reward prediction signals and (2) do not reflect signals of reward prediction error. These results provide novel insights into the neuronal circuitry potentially involved in computing reward prediction errors. The integrative approach of behavioral analysis, image analysis, pupillometry, and pharmacological manipulation used in this study will pave the way for understanding the psychological and neurobiological mechanisms of prediction and the prediction errors essential in learning and behavior.

animal behavior and cognition↗

bioRxiv2022

Differential effects of oxytocin receptor antagonist on social rank and other social behavior in mice

Oxytocin receptor signaling has been implicated in diverse social behaviors, but whether its behavioral effects depend on social tasks and an individual's position within a hierarchy remains unclear. We examined the effects of systemic administration of L-368,899, a blood-brain barrier-penetrating oxytocin receptor antagonist, across four domains of social behavior in male C57BL/6J mice: social rank, sex preference, general social preference, and dyadic interaction. Following the establishment of stable hierarchies in the tube test, administration of L-368,899 (10 mg/kg, intraperitoneally) to first-ranked mice did not alter their hierarchical position. Rank fluctuations were observed more frequently when the antagonist was administered to second-ranked mice. In both rank conditions, the remaining cage mates received saline. In the sex-preference task, saline-treated males spent more time in the female stimulus zone than in the male stimulus zone, whereas this preference was not statistically detectable following treatment with L-368,899 (3 or 10 mg/kg). In contrast, L-368,899 did not significantly alter proximity-based preference for a novel male over a nonsocial object or affect contact duration and inter-individual distance during dyadic interactions between familiar male cage mates, in which both members of each pair received the same treatment. Thus, systemic oxytocin receptor blockade did not produce a generalized reduction in social approach. Instead, the observed behavioral patterns suggest that its effects depend on specific social behavioral tasks and hierarchical position. These findings provide a pharmacological basis for further investigation of the task- and rank-dependent contributions of oxytocin receptor signaling to social behavior.

neuroscience↗

bioRxiv2021

Habit formation viewed as structural change in the behavioral network

Habit formation is a process in which an action becomes involuntary. While goal-directed behavior is driven by its consequences, habits are elicited by a situation rather than its consequences. Existing theories have proposed that actions are controlled by corresponding two distinct systems. Although canonical theories based on such distinctions are starting to be challenged, a few theoretical frameworks that implement goal-directed behavior and habits within a single system. Here, we propose a novel theoretical framework by hypothesizing that behavior is a network composed of several responses. With this framework, we have shown that the transition of goal-directed actions to habits is caused by a change in a single network structure. Furthermore, we confirmed that the proposed network model behaves in a manner consistent with the existing experimental results reported in animal behavioral studies. Our results revealed that habit could be formed under the control of a single system rather than two distinct systems. By capturing the behavior as a single network change, this framework provides a new perspective on studying the structure of the behavior for experimental and theoretical research. Author summaryTo obtain the desired consequences, organisms need to respond based on the knowledge of the consequences obtained by the response and the change in the environment caused by it. Such a process is called goal-directed behavior, which is flexible, but requires high computational cost. Once the same response is repeatedly performed under the same environment, the response becomes automatic, and transforms into a habit. In the canonical views, such a change from goal-directed response to habit was explained by the associative structures between the corresponding systems, goal-directed, and habit systems. However, the dichotomy in the mechanisms of behavior between goal-directed responses and habits has recently been challenged. Here, we show that, instead of assuming two explicitly distinguished mechanisms as in the canonical views, behavior is regarded as a network consisting of multiple responses, and that changes in the structure of the network cause two behavioral features, goal-directed behavior and habit. The transition from goal-directed behavior to habit has been operationally defined by sensitivity to the reward obtained by the response. We replicate such an experimental paradigm in the simulation and show that the behavioral network model can reproduce the empirical results on habit formation obtained from animal experiments. Our results demonstrate that habit formation can be explained in terms of changes in the network structure of behavior without assuming explicitly distinct systems and thus, provide a new theoretical framework to study the psychological, biological, and computational mechanisms of the behavior.

animal behavior and cognition↗

bioRxiv2018

The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster

ObjectivesWe hypothesized that systemic administration of high-mobility group box 1 fragment attenuates the progression of myocardial fibrosis and cardiac dysfunction in a hamster model of dilated cardiomyopathy by recruiting bone marrow mesenchymal stem cells thus causing enhancement of a self-regeneration system.\n\nMethodsTwenty-week-old J2N-k hamsters, which are {delta}-sarcoglycan-deficient, were treated with systemic injection of high-mobility group box 1 fragment (HMGB1, n=15) or phosphate buffered saline (control, n=11). Echocardiography for left ventricular function, cardiac histology, and molecular biology were analyzed. The life-prolonging effect was assessed separately using the HMGB1 and control groups, in addition to a monthly HMGB1 group which received monthly systemic injections of high-mobility group box 1 fragment, 3 times (HMGB1, n=11, control, n=9, monthly HMGB1, n=9).\n\nResultsThe HMGB1 group showed improved left ventricular ejection fraction, reduced myocardial fibrosis, and increased capillary density. The number of platelet-derived growth factor receptor-alpha and CD106 positive mesenchymal stem cells detected in the myocardium was significantly increased, and intra-myocardial expression of tumor necrosis factor stimulating gene 6, hepatic growth factor, and vascular endothelial growth factor were significantly upregulated after high-mobility group box 1 fragment administration. Improved survival was observed in the monthly HMGB1 group compared with the control group.\n\nConclusionsSystemic high-mobility group box 1 fragment administration attenuates the progression of left ventricular remodeling in a hamster model of dilated cardiomyopathy by enhanced homing of bone marrow mesenchymal stem cells into damaged myocardium, suggesting that high-mobility group box 1 fragment could be a new treatment for dilated cardiomyopathy.

molecular biology↗