Eric B. Keverne

Are subordinates always stressed? a comparative analysis of rank differences in cortisol levels among primates

Among primate species there is pronounced variation in the relationship between social status and measures of stress physiology. An informal meta-analysis was designed to investigate the basis of this diversity across different primate societies. Species were included only if a substantial amount of published information was available regarding both social behavior and rank-related differences in stress physiology. Four Old World and three New World species met these criteria, including societies varying from small-group, singular cooperative breeders (common marmoset and cotton top tamarin) to large-troop, multi-male, multi-female polygynous mating systems (rhesus, cynomolgus, talapoin, squirrel monkeys, and olive baboon). A questionnaire was formulated to obtain information necessary to characterize the stress milieu for individuals in particular primate societies. We standardized cortisol values within each species by calculating the ratio of basal cortisol concentrations of subordinates to those of dominants in stable dominance hierarchies and expressing the ratio as a percentage (relative cortisol levels). The meta-analysis identified two variables that significantly predicted relative cortisol levels: subordinates exhibited higher relative cortisol levels when they (1). were subjected to higher rates of stressors, and (2). experienced decreased opportunities for social (including close kin) support. These findings have important implications for understanding the different physiological consequences of dominant and subordinate social status across primate societies and how social rank may differ in its behavioral and physiological manifestations among primate societies.

Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest

Mest (also known as Peg1), an imprinted gene expressed only from the paternal allele during development, was disrupted by gene targeting in embryonic stem (ES) cells. The targeted mutation is imprinted and reversibly silenced by passage through the female germ line. Paternal transmission activates the targeted allele and causes embryonic growth retardation associated with reduced postnatal survival rates in mutant progeny. More significantly, Mest-deficient females show abnormal maternal behaviour and impaired placentophagia, a distinctive mammalian behaviour. Our results provide evidence for the involvement of an imprinted gene in the control of adult behaviour.

Beta-endorphin concentrations in cerebrospinal fluid of monkeys are influenced by grooming relationships

Social relationships are integral to the behaviour of many mammalian species. Primates are unusual in that their social relationships are extensive within groups, which often contain many reproductively active males and females. Several hypotheses have been forwarded to explain the ultimate causation of primate sociality. While attention has focused on grooming as a proximate factor influencing social relationships, the neural basis of such behaviour has not been investigated in monkeys. This report presents changes in the brains opioid system contingent on grooming in monkeys. Opiates themselves have a feedback interaction with grooming behaviour, as revealed from the administration of opiate agonists and antagonists. Opiate receptor blockade increases the motivation to be groomed, while morphine administration decreases it. These data support the view that brain opioids play an important role in mediating social attachment and may provide the neural basis on which primate sociality has evolved.

Something in the Air? New Insights into Mammalian Pheromones

Olfaction is the dominant sensory modality for most animals and chemosensory communication is particularly well developed in many mammals. Our understanding of this form of communication has grown rapidly over the last ten years since the identification of the first olfactory receptor genes. The subsequent cloning of genes for rodent vomeronasal receptors, which are important in pheromone detection, has revealed an unexpected diversity of around 250 receptors belonging to two structurally different classes. This review will focus on the chemical nature of mammalian pheromones and the complementary roles of the main olfactory system and vomeronasal system in mediating pheromonal responses. Recent studies using genetically modified mice and electrophysiological recordings have highlighted the complexities of chemosensory communication via the vomeronasal system and the role of this system in handling information about sex and genetic identity. Although the vomeronasal organ is often regarded as only a pheromone detector, evidence is emerging that suggests it might respond to a much broader variety of chemosignals.

Genomic imprinting and the differential roles of parental genomes in brain development

Certain genes are expressed either from the maternal or the paternal genome as a result of genomic imprinting, a process that confers functional differences on parental genomes during mammalian development. In this study we focus on the cumulative effects of imprinted genes on brain development by examining the fate of androgenetic (Ag: duplicated paternal genome) and parthenogenetic/gynogenetic (Pg/Gg: duplicated maternal genome) cells in chimeric embryos. Striking cell autonomous differences in the phenotypic properties of the uniparental cells were observed. Ag cells contributed substantially to the hypothalamic structures and not the cortex. By contrast, Pg/Gg cells contributed substantially to the cortex, striatum and hippocampus but not to the hypothalamic structures. Furthermore growth of the brain was enhanced by Pg/Gg and retarded by Ag cells. We propose that genomic imprinting may be responsible for a change in strategy controlling brain development in mammals. In particular, genomic imprinting may have facilitated a rapid non-linear expansion of the brain, especially the cortex, during development over evolutionary time.

Coadaptation in mother and infant regulated by a paternally expressed imprinted gene

This study investigates how a targeted mutation of a paternally expressed imprinted gene regulates multiple aspects of foetal and post–natal development including placental size, foetal growth, suckling and post–natal growth, weaning age and puberty onset. This same mutation in a mother impairs maternal reproductive success with reduced maternal care, reduced maternal food intake during pregnancy, and impaired milk let–down, which in turn reduces infant growth and delays weaning and onset of puberty. The significance of these coadaptive traits being synchronized in mother and offspring by the same paternally expressed imprinted gene ensures that offspring that have extracted ‘good’ maternal nurturing will themselves be both well provisioned and genetically predisposed towards ‘good’ mothering.

Vasopressin, oxytocin and social behaviour

Understanding the neurobiology of social behaviour in mammals has been considerably advanced by the findings from two species of vole, one of which is monogamous and pair bonds whereas the other species is promiscuous and fails to form any long-lasting social relationships. The combination of neurobehavioural studies and molecular genetics has determined behavioural differences between the two species linked to the neural distribution of vasopressin 1A receptor in the male brain. More importantly, vasopressin 1A receptor gene transfer including the upstream regulatory sequence has enhanced male social affiliation in a non-monogamous species. Male affiliative bonding depends upon release of both vasopressin and dopamine in the ventral striatum enhancing the reward value of odour cues that signal identity.

Cerebrospinal Fluid Levels of Acetylcholinesterase, Monoamines and Oxytocin during Labour, Parturition, Vaginocervical Stimulation, Lamb Separation and Suckling in Sheep

Acetylcholinesterase (AChE) activity, and concentrations of monoamines, monoamine metabolites and oxytocin (OT) were measured in the cerebrospinal fluid (CSF) of sheep during late pregnancy, labour, parturition, vaginocervical stimulation, lamb separation and suckling. Concentrations of AChE, 4-hydroxy-3 methoxyphenylethan-1,2-diol (MHPG) and OT were significantly elevated during labour and parturition. OT levels were also significantly raised in cycling ewes given vaginocervical stimulation. Separation of the ewes from their lambs (0.5-2 h) caused significant increases in AChE and MHPG, but not in OT. During suckling, following reunion of the ewes and lambs, concentrations of AChE and OT were significantly raised. The dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly lower in CSF during late pregnancy than during parturition and post-partum. Intravenous injections of OT which produced high circulating levels of this hormone in plasma produced significant, but very small, increases in concentrations of OT in the CSF. Our results show that in the sheep, labour, parturition, suckling and vaginocervical stimulation provoke a release of OT in the brain similar to that in the peripheral circulation. Changes in CSF levels of AChE and MHPG during labour, parturition and lamb separation, but not during vaginocervical stimulation, may be related to stress or hypertension.

Intracranial dialysis measurement of oxytoxin, monoamine and uric acid release from the olfactory bulb and substantia nigra of sheep during parturition, suckling, separation from lambs and eating ☆

Intracranial dialysis was used to measure the release of oxytocin (OXY), monoamines and their metabolites and uric acid (UA) from the substantia nigra (SN) and olfactory bulb (OB) of sheep during parturition, suckling, separation from lambs and eating. Results showed that OXY concentrations increased significantly during parturition, suckling and eating in the SN and during parturition and suckling in the OB. Concentrations of dopamine (DA) increased significantly in the SN during suckling and eating and in the OB during parturition and suckling. The dopamine metabolite, homovanillic acid, also increased significantly in the SN during parturition. Concentrations of the noradrenaline metabolite, 4-hydroxy-3-methoxyphenylethan-1,2-diol (MHPG) and the purine metabolite, UA, were significantly raised during parturition, suckling and separation from the lambs in the SN and increased UA levels were also found during eating. In a separate experiment it was confirmed that OXY was detectable in homogenates of both the SN and the OB. These results show that, in the sheep, OXY and DA release in the SN is associated with maternal and ingestive behaviour whereas similar release in the OB may only be related to maternal behaviour. Release of MHPG in the SN may be associated with maternal behaviour and/or stress.

Mother-infant bonding and the evolution of mammalian social relationships

A wide variety of maternal, social and sexual bonding strategies have been described across mammalian species, including humans. Many of the neural and hormonal mechanisms that underpin the formation and maintenance of these bonds demonstrate a considerable degree of evolutionary conservation across a representative range of these species. However, there is also a considerable degree of diversity in both the way these mechanisms are activated and in the behavioural responses that result. In the majority of small-brained mammals (including rodents), the formation of a maternal or partner preference bond requires individual recognition by olfactory cues, activation of neural mechanisms concerned with social reward by these cues and gender-specific hormonal priming for behavioural output. With the evolutionary increase of neocortex seen in monkeys and apes, there has been a corresponding increase in the complexity of social relationships and bonding strategies together with a significant redundancy in hormonal priming for motivated behaviour. Olfactory recognition and olfactory inputs to areas of the brain concerned with social reward are downregulated and recognition is based on integration of multimodal sensory cues requiring an expanded neocortex, particularly the association cortex. This emancipation from olfactory and hormonal determinants of bonding has been succeeded by the increased importance of social learning that is necessitated by living in a complex social world and, especially in humans, a world that is dominated by cultural inheritance.