Takefumi Kikusui

• Azabu University

The mental health of adolescents is an important issue, since it has a significant impact on their future lives. In this regard, one of the methods for supporting adolescents’ mental health is the interaction with companion animals, which is becoming widely recognized. In our previous research, we showed that owning companion animals has positive e...

Emotional contagion occurs in many animals, including rodents. To determine the social signals of emotional state-matching between individuals in mice, we conducted an empirical laboratory experiment using visual, olfactory and auditory stimuli. The Japanese wild-derived mouse strain MSM/Ms (MSM) was tested as observers, since our initial experimen...

Copy number variants (CNVs) are robustly associated with psychiatric disorders and changes in brain structures. However, because CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans and mouse models, it is unknow...

Behavioral and physiological synchrony facilitate emotional closeness in attachment relationships. The aim of this pseudorandomized cross-over study was to investigate the emotional and physiological link, designated as co-modulation, between dogs and their owners. We measured the heart rate variability (HRV) and physical activity of dogs belonging...

Introduction The One Health concept is a comprehensive understanding of the interaction between humans, animals, and the environment. The cohabitation of humans and pets positively affects their physical, mental, and social well-being. It is recognized as an essential factor from the One Health perspective. Furthermore, a healthy balance in the gut...

It is well known that dogs are capable of following human verbal instructions. However, very little is known about the equivalent ability in cats. In this study, we used a switched stimuli task to examine whether cats rapidly form picture-word association, which is a fundamental ability for word learning. We presented cats with two meaningless pict...

Adolescents who own dogs have higher well-being than those who do not; however, it is unclear how dog ownership affects adolescents’ well-being. As dog ownership influences the composition of the microbiota in the home environment, we examined the microbiome of dog-owning adolescents and analyzed associations with mental health and behavior. Our fi...

Background The gut microbiota plays an important role in the development of behavior and immunity in infants and juveniles. Early weaning (EW), a form of social stress in mice, leads to increased anxiety and an enhanced stress response in the hypothalamic-pituitary-adrenal axis during adulthood. Early life stress also modulates the immune system an...

The sleep-wake cycle represents a crucial physiological process essential for maintaining homeostasis and promoting individual growth. In dogs, alterations in sleep patterns associated with age and dog’s correlation with temperament factors, such as nervousness, have been reported, and there is an increasing demand for precise monitoring of sleep a...

Introduction The One Health concept is a comprehensive understanding of the interaction between humans, animals, and the environment. The cohabitation of humans and dogs positively affects their physical, mental, and social well-being. It is recognized as an essential factor from the One Health perspective. Furthermore, a healthy balance in the gut...

Background: The gut microbiota plays an important role in the development of behavior and immunity in infants and juveniles. Early weaning (EW), a form of social stress in mice, leads to increased anxiety and an enhanced stress response in the hypothalamic-pituitary-adrenal axis during adulthood. Early life stress also modulates the immune system a...

The emotional reactivity hypothesis predicts that reduced fear and aggression in domesticated animals improves their social cognitive abilities toward humans. However, no studies in dogs (Canis familiaris) have shown that higher individual temperament is associated with higher social cognitive abilities, such as human pointing. In this study, we fi...

The number of mothers suffering from mental illness is increasing steadily, particularly under conditions of the coronavirus pandemic. The identification of factors that contribute to resilience in mothers is urgently needed to decrease the risks of poor physical and psychological health. We focused on the risk of parenting stress and psychological...

The matrilineal transmission of maternal behavior has been reported in several species. Studies, primarily on rats, have suggested the importance of postnatal experience and the involvement of epigenetic mechanisms in mediating these transmissions. This study aims to determine whether the matrilineal transmission of maternal behavior occurs in mice...

One out of every five people in Japan is dissatisfied with their sleep and various diseases caused by lack of exercise have been pointed out, but there are few effective remedies for these problems. In this study, we aimed to develop a simple method for measuring behavioral sleep patterns and physical activity using a beacon accelerometer wirelessl...

Many animal species, including mice, form societies of numerous individuals for survival. Understanding the interactions between individual animals is crucial for elucidating group behavior. One such behavior in mice is huddling, yet its analysis has been limited. In this study, we propose a cost‐effective method for monitoring long‐term huddling b...

Introduction Late adolescence is a crucial period during which individuals connect with new communities. Furthermore, their mental health has lasting effects on their overall well-being. Involvement with family and the local community plays a significant role in shaping adolescents’ personalities and well-being. Additionally, pets, such as dogs and...

The number of mothers suffering from mental illness is increasing steadily, particularly under conditions of the coronavirus disease pandemic. The identification of factors that contribute to resilience in mothers is urgently needed to decrease the risks of poor physical and psychological functioning. We focused on the risk of parenting stress and...

Simple Summary COVID-19 has had both physical and mental health effects stemming, in particular, from lockdowns. Furthermore, these physical and mental effects have impacted not only people’s lives but also the lives of their pets, which in recent years have often been seen as members of the family. This study aimed to investigate whether the COVID...

Copy number variants (CNVs) are robustly associated with psychiatric disorders and their dimensions and changes in brain structures and behavior. However, as CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans a...

Copy number variants (CNVs) are robustly associated with psychiatric disorders and their dimensions and changes in brain structures and behavior. However, as CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans a...

The affiliative relationship between humans and dogs is compared to a mother–infant attachment relationship. We hypothesized that dog’s attachment behavior in negative emotional state aroused the owner’s attention toward the dog, that is, reduced parasympathetic activity. We measured heart rate variability in both dogs and humans during the Strange...

Previous studies have demonstrated that paternal caregiving behaviors are reliant on neural pathways similar to those supporting maternal care. Interestingly, a greater variability exists in parental phenotypes in men than in women among individuals and mammalian species. However, less is known about when or how such variability emerges in men. We...

Simple Summary Cats are the most widely kept companion animal in the world. Various factors influence the sociality of cats. Here, we investigated whether the hormonal status of cats, and the age at which they began living with a human, affected their behaviors toward humans. The results showed that male cats that began living with a human earlier...

Common marmosets have been widely used in biomedical research for years. Nutritional control is an important factor in managing their health, and insect intake would be beneficial for that purpose because common marmosets frequently feed on insects in natural habitats. Here, we examined the effect of enhanced insect feeding on the gut by analysing...

Simple Summary Cats (Felis silvestris catus) live with humans as domesticated animals. However, it is not clear how they have evolved from African wildcats (Felis silvestris lybica) through domestication. In this study, we compared the facial morphology of cats and wildcats to determine how the facial morphology of cats has changed in relation to t...

During the process of sexual evolution, mammals have acquired different reproductive and social roles for males and females. Differences in the cost of sperm and egg have given rise to differences in the reproductive strategies of males and females. For example, distinct sex differences are observed in mating forms and investment in fostering. It c...

We examined whether dogs show emotional response to social stimuli played on videos. Secondary, we hypothesized that if dogs recognize themselves in videos, they will show a different emotional response to videos of self and other dogs. We compared heart rate variability among four video stimuli: a video of the owner ignoring another dog (OW-A-IGN)...

Sensory signals are critical to perform adaptive social behavior. During copulation, male mice emit ultrasonic vocalizations (USVs). Our previous studies have shown that female mice exhibit approach behavior toward sound sources of male USVs and that, after being exposed to a male pheromone, exocrine gland-secreting peptide 1 (ESP1), female mice ex...

The population of postpartum women suffering from mental illness is increasing steadily, particularly under conditions of the COVID-19 pandemic. Identifying factors that contribute to resilience in postpartum women is urgently needed to decrease risks of poor physical and psychological functioning. Studies have linked variations in the intestinal m...

In humans, tear volume increases during emotional arousal. To our knowledge, no previous studies have investigated the relationship between emotional arousal and tear volume in animals. We performed the Schirmer tear test (STT) and measured tear volume in dogs before and after reunions with owners and familiar non-owners. Tear volume increased sign...

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmission, such as emotion and cognition. To dir...

Domestic cats (Felis silvestris catus) can live in high densities, although most feline species are solitary and exclusively territorial animals; it is possible that certain behavioral strategies enable this phenomenon. These behaviors are regulated by hormones and the gut microbiome, which, in turn, is influenced by domestication. Therefore, we in...

The dog ( Canis familiaris ) was the first domesticated animal and hundreds of breeds exist today. During domestication, dogs experienced strong selection for temperament, behaviour, and cognitive ability. However, the genetic basis of these abilities is not well-understood. We focused on ancient dog breeds to investigate breed-related differences...

Humans communicate with each other through language, which enables us talk about things beyond time and space. Do non-human animals learn to associate human speech with specific objects in everyday life? We examined whether cats matched familiar cats’ names and faces (Exp.1) and human family members’ names and faces (Exp.2). Cats were presented wit...

Physiological measurements of dogs' emotional states during human-animal interactions are essential for understanding the underlying biological relationship. Heart rate measured by electrocardiogram (ECG) can be used for the physiological measurement of emotional state. Soft disposable electrodes, which can be purchased commercially and reduce the...

In many species, the allocation of exploration and exploitation responses to environmental stimuli is important for survival. In this exploratory study, we determined whether dogs (Canis familiaris) explored novel stimuli in a visual discrimination task using food reinforcers. Initially, the dogs were trained with two pairs of simultaneous visual d...

In humans, tear volume increases in emotional arousal. No studies have investigated the relationship of emotional arousal and tear volume in animals. We measured tear volume in dogs before and after reunion with their owners. Tear volume increased significantly during owner, but not familiar non-owner, reunions but not during reunions with familiar...

Tears are an exocrine physiological fluid secreted onto the ocular surface from the lacrimal apparatus in all mammals. Limited research has been conducted on the functional neuronal circuitry of tear production. In particular, the neuronal mechanisms of emotional tearing, which is a physiological reaction harmonized with enhanced emotional arousal...

Research on canine guidance using spotlight stimulation is vital for the working canine mission. However, it is challenging to generate a spotlight with brighter illuminance using the presently available LED for easy detection of the spotlight by a canine. The limitation is due to the weight and size constraint for spotlight mounting on a canine, w...

To understand and enhance the working dog’s activity performance, studies that grasp the dog’s positive and negative emotions related to its motivation are gaining a lot of attention. For estimating a dog’s emotion, heart rate variability is studied by observing its characteristic fluctuation. So, by preparing a dog’s emotion, a discriminator can b...

Previous studies have demonstrated that paternal caregiving behaviours are reliant on neural pathways similar to those supporting maternal care. Interestingly, a greater variability exists in parental phenotypes in males than in females among individuals and mammalian species. However, less is known about when or how such variability emerges in hum...

Previous studies have demonstrated that paternal caregiving behaviours are reliant on neural pathways similar to those supporting maternal care. Interestingly, a greater variability exists in parental phenotypes in males than in females among individuals and mammalian species. However, less is known about when or how such variability emerges in hum...

The lateral prefrontal cortex (LPFC) has a strong monosynaptic connection with the caudate nucleus (CdN) of the striatum. Previous human MRI studies have suggested that this LPFC-CdN pathway plays an important role in inhibitory control and working memory. We aimed to validate the function of this pathway at a causal level by pathway-selective mani...

A prolonged stress hyporesponsive period (SHRP) due to the mother's presence may delay the timing of glucocorticoid (GC) elevation in infants, thereby reducing the excessive stress response that would affect post-growth temperament. In dogs, the SHRP has been suggested to persist until postnatal week (PW) 4; therefore, PW 5, which SHRP may be prolo...

Mammalian species form unique bonds between mothers and infants. Maternal care, including suckling, is necessary for infant survival, and the mother and, sometimes, the father require a lot of effort in nurturing infants. An infant's probability of survival depends on the extent of the investment of care by the mother. In parallel, mothers must ide...

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human diseas...

Maternal care, including by non-biological parents, is important for offspring survival1–8. Oxytocin1,2,9–15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress¹⁵. However, it is unclear how ini...

In vivo calcium imaging with genetically encoded indicators has recently been applied to macaque brains to monitor neural activities from a large population of cells simultaneously. Microendoscopic calcium imaging combined with implantable gradient index lenses captures neural activities from deep brain areas with a compact and convenient setup; ho...

The dog ( Canis familiaris ) was the first domesticated animal and hundreds of breeds exist today. During domestication, dogs experienced strong selection for temperament, behaviour, and cognitive ability. However, the genetic basis of these abilities is not well-understood. We focused on ancient dog breeds to investigate breed-related differences...

Common marmosets have been widely used in biomedical research for years. Nutritional control is an important factor in managing their health, and insect intake would be beneficial for that purpose because common marmosets frequently feed on insects in natural habitats. Here, we examined the effect of enhanced insect feeding on the gut by analysing...

Dogs are the oldest domesticated animals. The process of domestication of dogs is still unclear; however, they have established themselves as human partners and are sometimes more cooperative with humans than their conspecifics. In this study, to determine the effect of affiliative human presence on group behavior in dogs, we conducted short-time t...

Testosterone masculinizes male sexual behavior through an organizational and activational effects. We previously reported that the emission of ultrasonic vocalizations (USVs) in male mice was dependent on the organizational effects of testosterone; females treated with testosterone in the perinatal and peripubertal periods, but not in adults, had i...

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that alter monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmission, such as emotion and cognition. To dire...

In mice, early exposure to environmental odors affects social behaviors later in life. A signaling molecule, Semaphorin 7A (Sema7A), is induced in the odor-responding olfactory sensory neurons. Plexin C1 (PlxnC1), a receptor for Sema7A, is expressed in mitral/tufted cells, whose dendrite-localization is restricted to the first week after birth. Sem...

: Testosterone masculinizes male sexual behavior through an organizational effect during the perinatal period. We previously reported that the emission of ultrasonic vocalizations (USVs) in male mice was dependent on the organizational effects of testosterone; females treated with testosterone in the perinatal period had increased USV emissions com...

[This corrects the article DOI: 10.3389/fpsyg.2020.613512.].

The biological and psychological significance of oxytocin is increasingly recognized; however, reliable assays of oxytocin in biological samples have not been developed. We raised a new oxytocin polyclonal rabbit antibody against synthetic oxytocin. The affinity of antibodies to oxytocin was examined by a radio-immunoassay and compared with that of...

The human parenting brain network mediates caregiving behaviors. When exposed to the stimuli of their infants, compared with non-parents, both fathers and mothers exhibit distinct patterns of neural activation. As human males, relative to females, do not undergo robust physiological changes during pregnancy, when and how the paternal brain networks...

Dogs (Canis familiaris) and cats (Felis silvestris catus) have been domesticated through different processes. Dogs were the first domesticated animals, cooperating with humans by hunting and guarding. In contrast, cats were domesticated as predators of rodents and lived near human habitations when humans began to settle and farm. Although the domes...

Defensive behaviors are evolved responses to threat stimuli, and a potential threat elicits risk assessment (RA) behavior. However, neural mechanisms underlying RA behavior are hardly understood. Urocortin-3 (Ucn3) is a member of corticotropin-releasing factor peptide family and here, we report that Ucn3 neurons in the hypothalamic perifornical are...

Oxytocin has drawn significant research attention for its role in modulating mammalian social behavior. Despite generally conserved roles, oxytocin can function differently even in closely related species. Previous studies have shown that bonobos and chimpanzees, humans’ two closest relatives, demonstrate considerable behavioral differences, includ...

The purpose of this study is visualization of the search ability on different breeds and individuals for search and rescue dogs by using handler and dog behavior measurement suits. In this paper, to visualize the dog's search ability affected by multiple factors, the dog's movement speed, the amount of movement, the time spent finding victims, the...

Our research is canine guidance using spotlights. Using dogs' habit following light, a spotlight guidance suit can remotely guide dogs by switching spotlight irradiation. The problem was that the spotlight devices were long and could get caught in the dog's surrounding environment. In this study, we considered lenses with different focal lengths an...

Abstract The naked mole-rat (NMR) is a heterothermic mammal that forms eusocial colonies consisting of one reproductive female (queen), several reproductive males, and subordinates. Despite their heterothermy, NMRs possess brown adipose tissue (BAT), which generally induces thermogenesis in cold and some non-cold environments. Previous studies sugg...

Testosterone masculinizes male sexual behavior by providing organizational and activational effects during the perinatal and peripubertal periods and during adulthood, respectively. We revealed that the emission of ultrasonic vocalizations (USVs) and mounting behavior was regulated by different neural circuits. However, the detailed testosterone ef...

Deprivation of maternal care has been associated with higher pain sensitivity in offspring. In the present study, we hypothesized that the maternal licking/grooming behavior was an important factor for the development of the pain regulatory system. To test this hypothesis, we used male F2 offspring of early-weaned (EW) F1 mother mice that exhibit l...

Heart rate variability (HRV) is a physical and noninvasive index of the autonomic nervous system and has been used in a wide range of fields such as human medicine, veterinary and animal behavior. Measuring devices have been improved miniaturization and light-weighting and they make it possible to measure a dog's electrocardiogram (ECG) under a fre...

Breastfeeding behaviours can significantly change mothers' physiological and psychological states. The hormone oxytocin may mediate breastfeeding and mothers' emotion recognition. This study examined the effects of endogenous oxytocin fluctuation via breastfeeding on emotion recognition in 51 primiparous mothers. Saliva oxytocin was assessed before...

How the intrinsic sequence structure of neonatal mouse pup ultrasonic vocalization (USV) and maternal experiences determine maternal behaviors in mice is poorly understood. Our previous work showed that pups with a Tbx1 heterozygous (HT) mutation, a genetic risk for autism spectrum disorder (ASD), emit altered call sequences that do not induce mate...

How the intrinsic sequence structure of neonatal mouse pup ultrasonic vocalization (USV) and maternal experiences determine maternal behaviors in mice is poorly understood. Our previous work showed that pups with a Tbx1 heterozygous (HT) mutation, a genetic risk for autism spectrum disorder (ASD), emit altered call sequences that do not induce mate...

Obesity is a major risk factor for lifestyle-related diseases, including cardiovascular disease, type 2 diabetes, and hypertension. Several studies have investigated the association between pet ownership and obesity, but the findings have been inconsistent. This systematic literature review and meta-analysis assessed the association between pet own...

The naked mole-rat (NMR) is a poikilothermic mammal that forms eusocial colonies consisting of one breeding queen, several breeding kings, and subordinates. Despite their poikilothermic feature, NMRs possess brown adipose tissue (BAT), which in homeothermic mammals induces thermogenesis in cold environments. However, NMR-BAT thermogenic potential i...

Our early weaning schedule was associated with the emergence of trait anxiety in male rodents performing an elevated plus maze but not an open-field test. We previously reported that early weaning weakened excitatory neurotransmission to the amygdala from the prefrontal cortex, where the mesocorticolimbic dopaminergic (DAergic) fiber terminates on...

Recently, copying others’ behaviour has attracted attention among researchers. It aids individuals in reducing uncertainty about the knowledge of the environment and helps them in acquiring an adaptive behaviour at a lower cost than by learning it by themselves. Among the copying strategies, conformity, which is the copying of behavioural decisions...

Mammalian infants heavily depend on their mothers, and mother-infant interactions greatly influence neurobehavioral development. We have shown that early weaning consistently affect the emotional development in mice. Early-weaned mice show increased anxiety-like behaviors, heightened hypothalamic–pituitary–adrenal axis activity, and prolonged reduc...

Male mice emit ultrasonic vocalizations (USVs) in response to the presence of female mice and their urine. Male USVs attract females, enhancing female reproductive functions, and are thus considered as the courtship song. Previous studies have shown that female mice exhibit disassortative social preferences for male USVs. However, it remains unclea...

Microbiome composition has a pivotal role in neurobehavioral development. However, there is limited information about the role of the microbiome in sociability of mice in complex social contexts. Germ-free (GF) mice were reared in a microbiota-free environment until postnatal day 21 and then transferred to a room containing specific pathogen free (...

A potential association between pet ownership and mental well-being is suggested, but there is a shortage of high-quality longitudinal studies that consider probable differences among different species. We aimed to examine whether ownership of the most popular pets (dogs and cats) would predict mental well-being. The Tokyo Teen Cohort (TTC), a pros...

Oxytocin (OT) systems contribute to the elicitation of stereotypic maternal behaviors. OT peptide-expressing neurons are predominantly localized in the hypothalamus, whereas OT receptor (OTR)-expressing neurons are widely distributed throughout the brain. Among those OTR-expressing regions, the paraventricular thalamus (PVT) consists of heterogeneo...