Yu.E. Herbeck

Since 1959, the Russian Farm‐Fox study has bred foxes to be either tame or, more recently, aggressive, and scientists have used them to gain insight into the brain structures associated with these behavioral features. In mice, hippocampal area CA2 has emerged as one of the essential regulators of social aggression, and so to eventually determine whether we could identify differences in CA2 between tame and aggressive foxes, we first sought to identify CA2 in foxes (Vulpes vulpes). As no clearly defined area of CA2 has been described in species such as cats, dogs, or pigs, it was not at all clear whether CA2 could be identified in foxes. In this study, we cut sections of temporal lobes from male and female red foxes, perpendicular to the long axis of the hippocampus, and stained them with markers of CA2 pyramidal cells commonly used in tissue from rats and mice. We observed that antibodies against Purkinje cell protein 4 best stained the pyramidal cells in the area spanning the end of the mossy fibers and the beginning of the pyramidal cells lacking mossy fibers, resembling the pattern seen in rats and mice. Our findings indicate that foxes do have a “molecularly defined” CA2, and further, they suggest that other carnivores like dogs and cats might as well. With this being the case, these foxes could be useful in future studies looking at CA2 as it relates to aggression.

Domestication is one of the important evolutionary and genetic problems of biology. It addresses fundamental evolution aspects as well as allows us to study mechanisms of aggression, pro-social behavior and anthropogenesis. One of the potential key mechanisms of domestication may be associated with the central oxytocin (OT) system. OT has been repeatedly shown to exhibit pro-social and anxiolytic eff ects rodents, dogs, humans and other species [1]. In our study, we used intranasal OT administration on Siberian tame foxes and non-selected one. It is well-known experimental domestication model of. Th e OT eff ect on behavior had been investigated in intermale interactions (triple cage aft er adaptation) and human contact (new enclosure). OT administration increased patterns of playful (crouches on paws), affi liative (friendly) behavior, motor (fast move) and mixed activity in male-to-male interactions in tame foxes, whereas in case of unselected foxes, OT administration increased behavior patterns associated with anxiety (latent time for home cage exit, freezing, total time in home cage). In fox-human interactions, OT administration had the greatest eff ect on increasing the time tamed fox stayed at less than a meter away from a human. It is this parameter that is the defi ning one in similar tests on dogs. Th e results allow to suggest that OT has a context-dependent eff ect rather than explicitly pro-social eff ect in the tests, therefore amplifying the perception of social conditions according to the social salience hypothesis of OT. OT eff ect is associated with emotional positive and negative animal behaviors toward human that could be related to the genotype. Such OT eff ect might separate animals into more or less tolerant to humans under the same early domestication conditions.

Animal and plant domestication is one of the most remarkable cultural achievements in human evolution. The first animal to have been domesticated was the dog. Although related studies are many, little is known about the earliest times of its domestication. This review emphasizes that there are parallels in behavior change and its molecular genetic basis between domesticated foxes and dogs, with a special focus on the so-called “ancient” breeds. Three approaches to the study of the molecular genetic mechanisms of domestication are described and some of their results obtained with modern methods, including high-throughput sequencing, are given. One involves the experimental modeling of early domestication stages in the fox, a farmed animal; another, a comparative analysis of modern dogs and wolves; and yet another, a paleogenetic analysis of ancient dogs and wolves, with an account of their archaeological context. Phylogenetic and phylogeographical approaches to the study of dog domestication and their role in a comprehensive reconstruction of domestication mechanisms are discussed. Difficulties with timing estimates, the geographic position and the reconstruction of molecular mechanisms for dog domestication are considered in the context of sampling strategies for genomic analysis. Genes encoding the signaling system of glutamate receptors and neural crest cells, with their broad pleiotropic effect, are discussed as being the most important targets of selection in experimental and historical domestication. In conclusion, the need of supplementing the studies of domestication mechanisms with analyses of various developmental stages at the molecular and organismal levels is highlighted.

The publisher regret that they failed to include the Table 1 before the publication of the original version of this article. The table is presented in this article.

Animal domestication was an important stage in the human history, which coincided with or probably even promoted the advent of a turning point at which part of the humankind switched from hunting and gathering to husbandry. The leading factor in evolutionary changes at the dawn of domestication was probably selection for behavior towards humans: first natural (as the animals were habituating to a new ecological niche close to humans), then nonconscious, artificial. Selection was supposed to work on the systems that regulate behavior by reducing stress response and aggression and by inducing an emotionally positive response to humans. A possible role of the neuropeptides adrenocorticotropic hormone (ACTH), oxytocin (ОТ), arginine vasopressin (AVP), and their receptors is in the reduction in stress response and in the shaping of domestic behavior. Effects of oxytocin on the behavior of domestic animals have been actively explored in the last 10 years, with special focus on the dog. The results obtained so far suggest that this neuropeptide is substantially important for human-canine interactions, together with sex, amount of aggression experienced, and other factors. The study of AVP demonstrated its importance in aggression in domestic animals. This work lends support to the hypothesis that a substantial factor in the shaping of domestic behavior and in the reduction in stress-response might be selection for an enhanced activity of the central OT system and a reduced activity of the central AVP system, which have effects on ACTH and social behavior.

Стресс-реакция во многих случаях является одной из причин формирования агрессивного поведения как у животных, так и у человека. Ослабление стресс-ответа, по-видимому, существенно снижает агрессию по отношению к человеку у доместицированных животных. Однако механизмы этого снижения по-прежнему остаются далеко не ясны. В настоящей работе на экспериментальной модели доместикации, серебристо-черной лисице (Vulpes vulpes), полученной путем многолетнего отбора на реакцию к человеку, изучен ответ на стресс по уровню кортизола в крови у доместицируемых и агрессивных лисиц, вызванный 15-минутным удержанием на руках человека. Кроме того, у животных из этих поведенческих групп исследован один из важных механизмов глюкокортикоидной отрицательной обратной связи – экспрессия гена рецептора глюкокортикоидов (NR3C1) в гиппокампе. В работах последних лет существенное внимание уделяется различиям в профиле экспрессии микроРНК у животных с разными поведением и стресс-реакцией, а также микроРНК-регуляции экспрессии генов при стрессе, в том числе NR3C1. В этой работе проведен miRNA-seq анализ образцов участка дорзального гиппокампа. Показано, что удержание на руках человека вызывает глюкокортикоидный стресс-ответ как у доместицируемых, так и у агрессивных лисиц. При этом у агрессивных животных стресс-индуцированный уровень кортизола был достоверно выше по сравнению с доместицируемыми. В то же время различий экспрессии гена NR3C1 в дорзальном гиппокампе и профиле экспрессии микроРНК не обнаружено. Таким образом, снижение стресс-ответа при отборе лисиц на отсутствие агрессивной и проявление эмоционально-положительной реакции к человеку, по-видимому, не связано с такими важными механизмами регуляции, как изменение экспрессии гена NR3C1 и микроРНК-регуляция.

The neuropeptide oxytocin (OT) and its homologs are produced in specialized neurons located in vertebrates exclusively in a deep and evolutionarily old part of the forebrain, the hypothalamus. The axons of OT neurons form the classical hypothalamic-neurohypophyseal tract terminating in the blood vessels of the neurohypothysis to release OT into the system’s blood circulation. However, as was recently demonstrated in mammals, collaterals of OT axons concomitantly project to various forebrain regions to modulate the activity of the local networks. At the behavioral level, OT facilitates intraspecific social contacts in mammals via various mechanisms ranging from the suppression of neuroendocrine stress responses to direct OT action on the neurons of the socially relevant brain regions. Recent reports have indicated the possible contribution of OT to the formation of a social bond between domesticated mammals (dog, sheep, cattle) and humans. Indeed, the social interaction between humans and domesticated animals resulted in the elevation of peripheral OT levels (in blood, saliva, or urine) and, in congruence, exogenous (intranasal) OT application led to more frequent contacts between the owner and the domesticated animal. It has been known for decades that domesticated animals exhibit profound socio-communicative abilities accompanied by suppressed aggression and stress responsiveness. These peculiarities of their behavior and physiology may be influenced by the activity of the central OT system. Therefore, in the present mini review, we focus on the role of OT in the orchestration of distinct forms of social behavior, including the monogamous bond, maternal care, social memory and recognition, aggression, and anxiety. As a conclusion, we propose possible directions for exploring the OT contribution to the empathy between humans and domesticated animals, which was likely established in the course of their coevolution during last 10000–15000 years.

Animal domestication is a model of a rapid evolutionary process. In experimental fox domestication, the time required for the emergence and fixation of specific evolutionary changes was reduced from thousands to tens of years, compared to historical domestication. Tame foxes were obtained by extreme selective breeding for emotionally positive response toward humans. Unselected foxes, as well as foxes bred for enhanced aggressiveness to humans were used as control. Epigenetic regulation of gene expression is considered as one of the possible mechanisms of rapid evolution. In this study, expression of DNA methyltransferase genes, DNMT1 and DNMT3A, was investigated. It was demonstrated that, in tame foxes, the level of DNMT3A gene expression in the prefrontal cortex, hippocampus, and spleen was increased by more than 2 times in comparison with aggressive and unselected foxes. At the same time, the DNMT1 expression level did not differ among the studied groups of animals. A possible reason for the differences found in the DNMT3A expression could be the changes in the level and metabolism of methionine, which serves as a donor of methyl groups during DNA methylation. However, this study showed that there were no differences in the serum methionine levels between tame, unselected, and aggressive foxes. Thus, the data support the hypothesis that selection for positive emotional response toward humans affected the DNA methylation machinery.