田鼠属动物婚配制度的研究范式

从社会组织的生态格局、熟悉性、社会等级和交配近况等择偶行为的影响因子,性二型和雄性射精能力等个体特征,配对关系的神经内分泌机制几方面综述了田鼠动物婚配制度的研究进展,同时从生态学、比较心理学、生理学、神经生物学等方面探讨择偶行类节式的特点。生态学方法,用鼠动物具有完整的婚配制度多样性格局,是婚配制度比较研究的哺乳动物类群。运用比较心理学方法,通过择偶行为实验可直接比较单配制与较研究的理想哺乳动物类     

Oxytocin, vasopressin and pair bonding: implications for autism

Understanding the neurobiological substrates regulating normal social behaviours may provide valuable insights in human behaviour, including developmental disorders such as autism that are characterized by pervasive deficits in social behaviour. Here, we review the literature which suggests that the neuropeptides oxytocin and vasopressin play critical roles in modulating social behaviours, with a focus on their role in the regulation of social bonding in monogamous rodents. Oxytocin and vasopressin contribute to a wide variety of social behaviours, including social recognition, communication, parental care, territorial aggression and social bonding. The effects of these two neuropeptides are species-specific and depend on species-specific receptor distributions in the brain. Comparative studies in voles with divergent social structures have revealed some of the neural and genetic mechanisms of social-bonding behaviour. Prairie voles are socially monogamous; males and females form long-term pair bonds, establish a nest site and rear their offspring together. In contrast, montane and meadow voles do not form a bond with a mate and only the females take part in rearing the young. Species differences in the density of receptors for oxytocin and vasopressin in ventral forebrain reward circuitry differentially reinforce social-bonding behaviour in the two species. High levels of oxytocin receptor (OTR) in the nucleus accumbens and high levels of vasopressin 1a receptor (V1aR) in the ventral pallidum contribute to monogamous social structure in the prairie vole. While little is known about the genetic factors contributing to species-differences in OTR distribution, the species-specific distribution pattern of the V1aR is determined in part by a species-specific repetitive element, or 'microsatellite', in the 5' regulatory region of the gene encoding V1aR (avpr1a). This microsatellite is highly expanded in the prairie vole (as well as the monogamous pine vole) compared to a very short version in the promiscuous montane and meadow voles. These species differences in microsatellite sequence are sufficient to change gene expression in cell culture. Within the prairie vole species, intraspecific variation in the microsatellite also modulates gene expression in vitro as well as receptor distribution patterns in vivo and influences the probability of social approach and bonding behaviour. Similar genetic variation in the human AVPR1A may contribute to variations in human social behaviour, including extremes outside the normal range of behaviour and those found in autism spectrum disorders. In sum, comparative studies in pair-bonding rodents have revealed neural and genetic mechanisms contributing to social-bonding behaviour. These studies have generated testable hypotheses regarding the motivational systems and underlying molecular neurobiology involved in social engagement and social bond formation that may have important implications for the core social deficits characterizing autism spectrum disorders.     

Neural mechanisms of mother–infant bonding and pair bonding: Similarities,differences, and broader implications

This article is part of a Special Issue “Parental Care”.Mother–infant bonding is a characteristic of virtually all mammals. The maternal neural system may have provided the scaffold upon which other types of social bonds in mammals have been built. For example, most mammals exhibit a polygamous mating system, but monogamy and pair bonding between mating partners occur in ~ 5% of mammalian species. In mammals, it is plausible that the neural mechanisms that promote mother–infant bonding have been modified by natural selection to establish the capacity to develop a selective bond with a mate during the evolution of monogamous mating strategies. Here we compare the details of the neural mechanisms that promote mother–infant bonding in rats and other mammals with those that underpin pair bond formation in the monogamous prairie vole. Although details remain to be resolved, remarkable similarities and a few differences between the mechanisms underlying these two types of bond formation are revealed. For example, amygdala and nucleus accumbens–ventral pallidum (NA–VP) circuits are involved in both types of bond formation, and dopamine and oxytocin actions within NA appear to promote the synaptic plasticity that allows either infant or mating partner stimuli to persistently activate NA–VP attraction circuits, leading to an enduring social attraction and bonding. Further, although the medial preoptic area is essential for maternal behavior, its role in pair bonding remains to be determined. Our review concludes by examining the broader implications of this comparative analysis, and evidence is provided that the maternal care system may have also provided the basic neural foundation for other types of strong social relationships, beyond pair bonding, in mammals, including humans.     

幼体生长发育特征可导致橙腹田鼠的单配体制吗?

橙腹田鼠(Microtus ochrogaster)和草原田鼠(M. pennsylvanicus)是两种亲缘关系很近,但有着完全不同交配体制的田鼠。本文试图通过他们头骨的形态学比较来验证幼体生长发育(paedomorphosis)可以印证单配制交配体制进化的假说。通过几种头骨的测量,我们发现草原田鼠头骨的长与宽比例大于橙腹田鼠,说明前者具有相对狭长的头骨。进一步的测量发现,这种不同是由于草原田鼠具有相对较长的鼻骨造成的。最后,我们对同种内成年和幼年的头骨进行了比较,发现单配制的橙腹田鼠相对于多配制的草原田鼠,其成年的头骨与幼年的头骨更相似。这些测量结果说明与多配制的田鼠相比,单配制的田鼠在形态及行为上保留更多的幼年状态,而这种行为很可能与其交配体制有关。     

Comparative distribution of central neuropeptide Y (NPY) in the prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) vole

Neuropeptide Y (NPY) has been implicated as a modulator of social behavior, often in a species-specific manner. Comparative studies of closely related vole species are particularly useful for identifying neural systems involved in social behaviors in both voles and humans. In the present study, immunohistochemistry was performed to compare NPY-like immunoreactivity (-ir) in brain tissue of the socially monogamous prairie vole and non-monogamous meadow vole. Species differences in NPY-ir were observed in a number of regions including the cortex, extended amygdala, septal area, suprachiasmatic nucleus, and intergeniculate leaf. Meadow voles had higher NPY-ir in all these regions as compared to prairie voles. No differences were observed in the striatum or hippocampus. The extended amygdala and lateral septum are regions that play a key role in regulation of monogamous behaviors such as pair bonding and paternal care. The present study suggests NPY in these regions may be an additional modulator of these species-specific social behaviors. Meadow voles had moderately higher NPY-ir in a number of hypothalamic regions, especially in the suprachiasmatic nucleus. Meadow voles also had much higher levels of NPY-ir in the intergeniculate leaflet, another key region in the regulation of circadian rhythms. Overall, species differences in NPY-ir were observed in a number of brain regions implicated in emotion, stress, circadian, and social behaviors. These findings provide additional support for a role for the NPY system in species-typical social behaviors.     

Cellular mechanisms of social attachment

Pharmacological studies in prairie voles have suggested that the neuropeptides oxytocin and vasopressin play important roles in behaviors associated with monogamy, including affiliation, paternal care, and pair bonding. Our laboratory has investigated the cellular and neuroendocrine mechanisms by which these peptides influence affiliative behavior and social attachment in prairie voles. Monogamous prairie voles have a higher density of oxytocin receptors in the nucleus accumbens than do nonmonogamous vole species; blockade of these receptors by site-specific injection of antagonist in the female prairie vole prevents partner preference formation. Prairie voles also have a higher density of vasopressin receptors in the ventral pallidal area, which is the major output of the nucleus accumbens, than montane voles. Both the nucleus accumbens and ventral pallidum are key relay nuclei in the brain circuits implicated in reward, such as the mesolimbic dopamine and opioid systems. Therefore, we hypothesize that oxytocin and vasopressin may be facilitating affiliation and social attachment in monogamous species by modulating these reward pathways.     

单配制啮齿动物Pair Bond形成的神经调节机制

单配制啮齿动物社会结构的神经生物学原理可以通过实验室研究Social bonding而获得。在本文中,我们探讨了如何利用单配制的草原田鼠(Microtus ochrogaster)作为研究模型揭示pair bond形成的神经调控机制。我们进而探讨了单配制与多配制田鼠之间神经解剖学的差异以及神经化学物质的调节是怎样影响pair bond的。本篇综述还讨论了与pair bond形成有关的神经化学系统之间的相互影响以及pair bond形成过程中的两性差异。最后,我们预测了这一研究领域的未来研究方向以及研究social bonding的神经调控对人类健康的重要性。     

以田鼠作为动物模型来研究社会行为的进化:基因、脑与行为

田鼠属的一些近缘种间具有独特的社会行为多态性。例如Microtusochrogaster和M .pinetorum为一夫一妻制 ,而M .montanus和M .pennsylvanicus则为独居和一夫多妻制。无论是在野外还是人工饲养的条件下 ,单配制的田鼠其雌、雄成年个体一经交配即在两者之间形成长期的配偶关系并且双亲共同哺育后代。已证明神经多肽加压素 (Vasopressin)参与了田鼠单配制行为的神经调控。本篇综述了过去以及近期关于加压素调控田鼠配偶关系形成的研究结果和进展。首先 ,阐述了加压素V1a受体 (V1aR)在脑分布的种间差异 ,并以此来鉴别特定脑区在配偶关系形成中的功能 ;其次 ,探讨了运用V1aR拮抗物的药理学方法来决定究竟哪些脑区参与配偶关系的形成 ,还描述了田鼠种间V1aR基因结构和功能的不同 ,以及这些不同对V1aR在大脑的分布和行为调控潜在的作用机制 ;最后 ,讨论了最新的研究结果 ,即对一夫多妻制田鼠进行脑V1aR基因的改造 ,从而使之表现出一夫一妻制田鼠的行为。总之 ,了解复杂的社会性行为的遗传和神经机制可以加深我们对种间和种内行为分歧进化的理解     

The effects of mate removal on pregnancy success in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus).

The effects of removing the stud male have not been controlled in many studies relating pregnancy block to the presence of an unfamiliar male. We examined the effects of removing the male on pregnancy success in prairie voles and meadow voles, two species that differ in degree of paternal investment. Whereas prairie vole males provide extensive care to offspring and accelerate pup development, meadow vole males display little or no care and delay development of pups. We predicted that removal of the stud male would decrease pregnancy success in prairie voles and either have no effect or increase success in meadow voles. In experiment 1, females were in male-induced estrus, and their mates were either left with them or were removed 4 h, 1 day, 2 days, or 8 days after mating. In experiment 2, females were in postpartum estrus, and their mates were either left with them or were removed 1 day, 2 days, or 8 days after birth of their first litter. Removal of the male soon after mating in postpartum estrus decreased pregnancy success in prairie voles and increased success in meadow voles. Thus, although removal of the stud male influenced litter production, the direction of the effect varied with species.     

Multiple captures provide evidence of small mammal social behavior

Social behavior of small mammals living under natural conditions often is inferred from live-trapping data, particularly from incidents in which two or more individuals are captured together in a trap. We examined whether multiple-capture data from a long-term study of prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus) were consistent with well-known species differences in social behavior (whereas prairie voles are highly social and display monogamy, meadow voles are less social and promiscuous). When possible, we also examined multiple captures of two nontarget species, northern short-tailed shrews (Blarina brevicauda) and western harvest mice (Reithrodontomys megalotis). Percent of total captures that were multiple captures and percent of total adult captures that were male–female captures were highest for prairie voles and lowest for meadow voles; values for harvest mice and shrews were in between those of the vole species, but more similar to values for meadow voles. Repeat captures of the same male–female pair occurred most commonly in prairie voles, and multiple captures of this species typically involved individuals from the same social group. Multiple captures of adults and juveniles were more common in prairie voles than meadow voles, except for captures of at least one adult male and at least one juvenile, which did not differ between the two vole species. Multiple capture data for prairie voles and meadow voles were largely consistent with established species differences in social behavior, suggesting that such data can provide an accurate indication of social and mating systems of small mammals.     

小型田鼠:研究单配制进化与调控的模型

哺乳动物的单配制通常被认为是社会性单配制,它不是单纯地由性行为来决定,而是由诸多因素,包括长期的pair bond、夫妻双方共同抚育后代、免近亲交配以及雌雄两性相似等来决定的。在这篇综述中,我们论述了如何以啮齿类田鼠属(Microtus)为模型,通过比较研究来帮助我们理解社会性单配制的进化以及其神经调控机制。对田鼠属的研究不仅证实了单配制起源于艰苦的生存条件的假说,而且还证实了雌性性选择可能有利于维持单配制。不仅如此,哺乳动物单配制的进化还需要雄性的prosocial行为的不断强化。例如,亲近行为可以促进pairbond的形成并强化雄性对后代的哺育行为,而这种强化则来源于神经多肽催产素(OT)和加压素(AVP)与类固醇类激素的相互作用。催产素和加压素调控pairbond和双亲哺育行为的表达,而单配制和多配制田鼠的催产素和加压素受体在脑内的分布有显的不同。比较研究揭示了小型田鼠单配制的调控机制,而种内差异和行为上的可塑性则有助于我们进一步理解这种机制。比如,在某些条件下,多配制的草原田鼠(Microtus pennsylvanicu)的雄性个体具有哺育后代的行为。尽管草原田鼠的加压素Vla受体在脑内的分布与其他多配制的田鼠相似,但是如果脑室注射加压素,仍可以诱发其哺育后代的行为。同样是单配制的橙腹田鼠(Microtus ochrogaster),生活在：Illnois的显示出高水平的prosocial行为,而生活在Kansas的则表现出较低水平的社会性行为。即使两个种群的催产素或加压素Vla受体在脑内的分布相同,它们的雌激素受体表达水平显不同,这在雄性个体表现尤其明显。与Kansas的雄性个体相比,在终纹床核(bed rucleus of the stria tenninalis)和杏仁核中区(medial amygdala)这两个调控亲近行为和攻击行为的脑区,Illinois的雄性个体的α雌激素受体的水平要低得多。这些研究表明对雌激素的低敏感程度有利于高水平地表达prosocial行为并降低特定类型的攻击行为。     

Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles

Oxytocin (OT) is a deeply conserved nonapeptide that acts both peripherally and centrally to modulate reproductive physiology and sociosexual behavior across divergent taxa, including humans. In vertebrates, the distribution of the oxytocin receptor (OTR) in the brain is variable within and across species, and OTR signaling is critical for a variety of species-typical social and reproductive behaviors, including affiliative and pair bonding behaviors in multiple socially monogamous lineages of fishes, birds, and mammals. Early work in prairie voles suggested that the endogenous OT system modulates mating-induced partner preference formation in females but not males; however, there is significant evidence that central OTRs may modulate pair bonding behavior in both sexes. In addition, it remains unclear how transient windows of central OTR signaling during sociosexual interaction modulate neural activity to produce enduring shifts in sociobehavioral phenotypes, including the formation of selective social bonds. Here we re-examine the role of the central OT system in partner preference formation in male prairie voles using a selective OTR antagonist delivered intracranially. We then use the same antagonist to examine how central OTRs modulate behavior and immediate early gene (Fos) expression, a metric of neuronal activation, in males during brief sociosexual interaction with a female. Our results suggest that, as in females, OTR signaling is critical for partner preference formation in males and enhances correlated activation across sensory and reward processing brain areas during sociosexual interaction. These results are consistent with the hypothesis that central OTR signaling facilitates social bond formation by coordinating activity across a pair bonding neural network.     

Meadow Voles (Microtus pennsylvanicus) and Prairie Voles (M. ochrogaster) Differ in Their Responses to Over-Marks from Opposite- and Same-Sex Conspecifics

Over‐marking occurs when one individual deposits its scent mark on the scent mark of a conspecific. Previous studies have shown that meadow voles (Microtus pennsylvanicus) and prairie voles (M. ochrogaster) that were exposed to an over‐mark of two same‐sex conspecifics, later responded similarly to the top‐scent mark but differed in their response to the bottom‐scent mark. In the present study, we examined the responses of meadow voles and prairie voles to same‐sex and mixed‐sex over‐marks to ascertain whether their responses reflect the different tactics which males and females in promiscuous (meadow voles) and monogamous (prairie voles) species use to attract opposite‐sex conspecifics and to compete with same‐sex conspecifics. Males and females of both species spent more time investigating the mark of the top‐scent donor than that of the bottom‐scent donor of an over‐mark. Meadow voles exposed to a mixed‐sex over‐mark spent more time investigating the mark of the opposite‐sex conspecific independently of whether it was from the top‐ or bottom‐scent donor. In contrast, prairie voles spent more time investigating the mark of the opposite‐sex donor if it was from the top‐scent donor. These results suggest that: (i) over‐marking serves a competitive function; (ii) the scent marks of individuals attract multiple mates in promiscuous species such as the meadow vole; and (iii) the scent marks of individuals establish and maintain pair bonds between familiar opposite‐sex conspecifics in monogamous species such as the prairie vole.     

BAC-based sequencing of behaviorally-relevant genes in the prairie vole

The prairie vole (Microtus ochrogaster) is an important model organism for the study of social behavior, yet our ability to correlate genes and behavior in this species has been limited due to a lack of genetic and genomic resources. Here we report the BAC-based targeted sequencing of behaviorally-relevant genes and flanking regions in the prairie vole. A total of 6.4 Mb of non-redundant or haplotype-specific sequence assemblies were generated that span the partial or complete sequence of 21 behaviorally-relevant genes as well as an additional 55 flanking genes. Estimates of nucleotide diversity from 13 loci based on alignments of 1.7 Mb of haplotype-specific assemblies revealed an average pair-wise heterozygosity (8.4×10(-3)). Comparative analyses of the prairie vole proteins encoded by the behaviorally-relevant genes identified >100 substitutions specific to the prairie vole lineage. Finally, our sequencing data indicate that a duplication of the prairie vole AVPR1A locus likely originated from a recent segmental duplication spanning a minimum of 105 kb. In summary, the results of our study provide the genomic resources necessary for the molecular and genetic characterization of a high-priority set of candidate genes for regulating social behavior in the prairie vole.     

The neurobiology of social attachment: A comparative approach to behavioral, neuroanatomical, and neurochemical studies

The formation and maintenance of social bonds in adulthood is an essential component of human health. However studies investigating the underlying neurobiology of such behaviors have been scarce. Microtine rodents offer a unique comparative animal model to explore the neural processes responsible for pair bonding and its associated behaviors. Studies using monogamous prairie voles and other related species have recently offered insight into the neuroanatomical, neurobiological, and neurochemical underpinnings of social attachment. In this review, we will discuss the utility of the microtine rodents in comparative studies by exploring their natural history and social behavior in the laboratory. We will then summarize the data implicating vasopressin, oxytocin, and dopamine in the regulation of pair bonding. Finally, we will discuss the ways in which these neurochemical systems may interact to mediate this complex behavior.     

Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience.

Prairie voles (Microtus ochrogaster) exhibit a monogamous mating system characterized by long-term pair bonds between mates. The purpose of this study was to examine the effect of cohabitation time and sexual experience on the development of pair bond formation in female prairie voles. Females that were allowed to cohabit for 24 hr or more, with or without mating, exhibited a strong social preference for a familiar partner versus a strange male. Females that cohabited and mated for 6 hr showed strong preferences for a familiar partner, while cohabitation for less than 24 hr, without mating, did not result in preferences for the familiar male. These results indicate that mating was not essential for partner preference formation; however, preferences developed more rapidly when mating occurred.     

Male copulatory behavior and the induction of ovulation in female voles: a quest for species specificity.

Two experiments were conducted to investigate species specificity in the neuroendocrine responsiveness of female prairie voles to the copulatory patterns of males. In Experiment 1, prairie vole males mated for one ejaculatory series were not significantly more effective in inducing ovulation in prairie vole females than montane voles mated with prairie vole females for one series, two series, or to satiety. Mating with conspecific males did result in significantly more implanted embryos than did heterospecific matings. In Experiment 2, it was found that, when the amount of vaginal stimulation was both low and equated across groups, prairie vole males were significantly more effective in triggering ovulation in female prairie voles than were either meadow voles or montane voles. Although there appears to be some species specificity to the “vaginal codes” of these congeneric species, its biological significance is unclear.     

Field tests of cis-regulatory variation at the prairie vole avpr1a locus: association with V1aR abundance but not sexual or social fidelity

The neuropeptide vasopressin and its receptor V1aR are broadly implicated in social behavior and play a central role in several key aspects of male mating tactics in voles. In the prairie vole, a microsatellite in the cis-regulatory region of the gene encoding V1aR (avpr1a) provides a potential genetic basis for individual variation in neural phenotype and behavior; recent studies found that allele length predicts V1aR expression and male social attachment in the laboratory. Here, we explore the relationship between avpr1a microsatellite length, V1aR neural phenotype, and field measures of monogamy and fitness in male prairie voles. We found significant effects of allele length on V1aR expression in structures integral to pairbond formation. These effects did not, however, translate to differences in mating tactics or reproductive success. Together, these data suggest that, while length polymorphism in the avpr1a microsatellite influences neuronal phenotype, this variation does not contribute significantly to male reproductive success and field behavior. We propose that previously reported behavioral effects may be mediated primarily by sequence variation at this locus, for which allele length is an imperfect proxy. By combining genetic, neuronal and ecological approaches, these data provide novel insights into the contribution of genotype to natural diversity in brain and behavior.