Akira Tanave

Selection for reluctance to avoid humans during the domestication of mice

Many animal species have been domesticated over the course of human history and became tame as a result of domestication. Tameness is a behavioral characteristic with 2 potential components: (1) reluctance to avoid humans and (2) motivation to approach humans. However, the specific behavioral characteristics selected during domestication processes remain to be clarified for many species. To quantify these 2 different components of tameness separately, we established 3 behavioral tests: the ‘active tame’, ‘passive tame’ and ‘stay‐on‐hand’ tests. We subjected genetically diverse mouse strains to these tests, including 10 wild strains (BFM/2Ms, PGN2/Ms, HMI/Ms, BLG2/Ms, NJL/Ms, KJR/Ms, SWN/Ms, CHD/Ms, MSM/Ms and CAST/Ei), a fancy strain (JF1/Ms) and 6 standard laboratory strains (C3H/HeNJcl, CBA/J, BALB/cAnNCrlCrlj, DBA/2JJcl, 129+Ter/SvJcl and C57BL/6JJcl). To analyze the effects of domestication, these 17 strains were divided into 2 groups: domesticated strains (fancy and laboratory strains) and wild strains. Significant differences between strains were observed in all traits, and the calculated estimates of broad‐sense heritability were 0.15–0.72. These results illustrate that tameness in mice is significantly influenced by genetic background. In addition, they clearly show the differences in the features of tameness in domesticated and wild strains. Most of the domesticated strains showed significantly greater reluctance to avoid humans than wild strains, whereas there was no significant difference in the level of motivation to approach humans between these 2 groups. These results might help to clarify the genetic basis of tameness in mice.

Selective breeding and selection mapping using a novel wild-derived heterogeneous stock of mice revealed two closely-linked loci for tameness

Tameness is a major behavioral factor for domestication, and can be divided into two potential components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). We identified genetic loci for active tameness through selective breeding, selection mapping, and association analysis. In previous work using laboratory and wild mouse strains, we found that laboratory strains were predominantly selected for passive tameness but not active tameness during their domestication. To identify genetic regions associated with active tameness, we applied selective breeding over 9 generations for contacting, a behavioural parameter strongly associated with active tameness. The prerequisite for successful selective breeding is high genetic variation in the target population, so we established and used a novel resource, wild-derived heterogeneous stock (WHS) mice from eight wild strains. The mice had genetic variations not present in other outbred mouse populations. Selective breeding of the WHS mice increased the contacting level through the generations. Selection mapping was applied to the selected population using a simulation based on a non-selection model and inferred haplotype data derived from single-nucleotide polymorphisms. We found a genomic signature for selection on chromosome 11 containing two closely linked loci.

Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice

Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

Automated Estimation of Mouse Social Behaviors Based on a Hidden Markov Model

Recent innovations in sensing and Information and Communication Technology (ICT) have enabled researchers in animal behavior to collect an enormous amount of data. Consequently, the development of an automated system to substitute for some of the observations and analyses that are performed currently by expert researchers is becoming a crucial issue so that the vast amount of accumulated data can be processed efficiently. For this purpose, we introduce a process for the automated classification of the social interactive status of two mice in a square field on the basis of a Hidden Markov model (HMM). We developed two models: one for the classification of two states, namely, indifference and interaction, and the other for three states, namely, indifference, sniffing, and following. The HMM was trained with data from 50 pairs of mice as provided by expert human observers. We measured the performance of the HMM by determining its rate of concordance with human observation. We found that sniffing behavior was segmented well by the HMM; however, following behavior was not segmented well by the HMM in terms of percentage concordance. We also developed software called DuoMouse, an automated system for the classification of social interactive behavior of mice, that was based on the HMM. Finally, we compared two implementations of the HMM that were based on a histogram and a Gaussian mixture model.

Measuring Active and Passive Tameness Separately in Mice

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two behavioral components: a reluctance to avoid humans (passive tameness) and a motivation to approach humans (active tameness). To quantify these components in mice, we previously developed behavioral tests for active tameness, passive tameness, and the willingness to stay on a human hand, each designed to be completed within 3 min. The data obtained were used for selective breeding, with a large number of mice analyzed per generation. The active tameness test measures the movement of the mouse toward a human hand and the contact it engages in. The passive tameness test measures the duration of time that a mouse tolerates human touch. In the stay-on-hand test, a mouse is placed on a human hand and touched slowly using the thumb of that hand; the duration of time that the animal remains on the hand is measured. Here, we describe the test set-up and apparatus, explain the procedures, and discuss the appropriate data analysis. Finally, we explain how to interpret the results.

Genetic study of anxiety-like behaviors characteristic of wild mice

mesenteric afferent nerves in the rat. However, it is still unclear what receptor subtype of 5-HT activates on vagal celiac afferent activity. In the present study, we examined the effects of various 5-HT receptor subtype-specific agents on vagal celiac afferent activity and identified pharmacological characteristics involved in the activation of vagal celiac afferent fibers by 5-HT. Systemic administration (i.v.) of 5-HT evoked a transient and following a sustained activity of the vagal afferent. The transient vagal afferent activity was mimicked by 5-HT3 receptor agonist 1-phenylbiguanide (1-PBG) and blocked by 5-HT3 antagonist granisetron. The sustained vagal afferent activity was mimicked by 5-HT2 agonist -Methyl-5-hydroxytryptamine, but 5-HT2B/2C agonist m-CPP had no effect on the vagal afferent activity. In addition, 5-HT2A antagonist ketanserin inhibited the sustained vagal afferent activity, which was more inhibited by 5-HT1/2 antagonist methysergide. These results suggest that the increase in vagal celiac afferent activity represents the excitatory effects of 5-HT3, 5-HT1 and 5-HT2A receptors.