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Biomedical subjects

Eric B Keverne

Publications and source records attributed to Eric B Keverne.

12 recordsLinked to original sources
PubMed2006

Suppression of prolactin does not reduce infant care by parentally experienced male common marmosets (Callithrix jacchus).

High levels of prolactin have been found to correlate with the expression of paternal care in a variety of taxa. However, in mammals, there is little experimental evidence that prolactin is causally involved in the stimulation or maintenance of paternal care. Here, we suppressed prolactin production in paternally experienced common marmoset fathers in their family groups during the first 2 weeks after their infants were born. Circulating prolactin levels were suppressed using cabergoline (Dostinex: Pfizer), a long acting dopamine (D2) agonist with minimal behavioural side-effects. A within-subject design was used to compare behavioural and hormonal data on 5 paternally experienced fathers during two consecutive births. Cabergoline reduced prolactin to negligible levels in all fathers without effecting testosterone, DHT and cortisol and without adverse side-effects. However, lowering prolactin had no significant effect on the expression of majority of the behaviour patterns associated with paternal care. These included infant carrying, infant grooming and the frequency with which fathers retrieved and rejected infants. The only infant-related behaviour to be affected was the frequency with which fathers touched, licked and investigated infants. We noted a marginally significant increase in this behaviour during cabergoline treatment. Despite the lack of effect on paternal care, cabergoline did exert an effect on the affiliative/sexual behaviour of fathers as there was a significant increase in the grooming behaviour fathers directed at and received from their mates during drug treatment. This study showed that experienced male marmosets can express paternal behaviour in the absence of the high prolactin levels normally seen after infants are born.

Animals↗
PubMed2006

Urinary pheromones promote ERK/Akt phosphorylation, regeneration and survival of vomeronasal (V2R) neurons.

The G protein-coupled pheromone receptor neurons (V1R and V2R) of the vomeronasal organ (VNO) are continually replaced throughout the lifetime of the mouse. Moreover, active signalling of V2Rs via the transient receptor potential 2(TRPC2) channel is necessary for regeneration of receptors, as the TRPC2 null mutant mouse showed a 75% reduction of V2Rs by the age of two months. Here we describe V2R mediated signalling in a neuronal line established from vomeronasal stem cells taken from postnatal female mice. Cells were immunoreactive for Galpha(o) and V2R, whereas V1R and Galpha(i) immunoreactivity could not be detected. Biological ligands (dilute urine and its protein fractions) were found to increase proliferation and survival of these neurons. Dilute mouse urine but not artificial urine also induced ERK, Akt and CREB signalling in a dose dependent way. The volatile fraction of male mouse urine alone was without effect while the fraction containing peptides (> 5 kDa) also stimulated ERK and Akt phosphorylation. The ERK, Akt and CREB phosphorylation response was sensitive to pertussis toxin, confirming the involvement of V2R linked Galpha(o). Dilute mouse urine or its high molecular weight protein fraction increased survival and proliferation of these neurons. Hence, urinary pheromones, which signal important social information via mature neurons, also promote survival and proliferation of their regenerating precursors. These data show that regenerating V2Rs respond to urine and the urinary peptides by activation of the Ras-ERK and PI3-Akt pathways, which appear to be important for vomeronasal neural survival and proliferation.

Analysis of Variance↗
PubMed2005

Genes, brains and mammalian social bonds.

Recent studies of monogamous species have revealed the role of the neuropeptides oxytocin and vasopressin in activating reward mechanisms of the brain that are involved in establishing partner recognition and selective 'bonding'. The evolutionary history of these findings resides, at a mechanistic level, in the reciprocal bonding between mother and infant that is common to all mammals. However, in Old World primates, where mother and infant alone would not survive, living in large social groups brings extended family relationships and provides for alloparenting. This has required the emancipation of parenting behaviour from the constraints of hormonal state and the evolution of large brains for decision making that was previously restricted and determined by hormonal state. How this has been achieved, what conserved mechanisms underpin social bonding, and what genetic and mechanistic changes have occurred in the evolution of social bonds are the issues addressed here.

Journal Article↗
PubMed2004

Understanding well-being in the evolutionary context of brain development.

Much of the work on well-being and positive emotions has tended to focus on the adult, partly because this is when problems are manifest and well-being often becomes an issue by its absence. However, it is pertinent to ask if early life events might engender certain predispositions that have consequences for adult well-being. The human brain undergoes much of its growth and development postnatally until the age of seven and continues to extend its synaptic connections well into the second decade. Indeed, the prefrontal association cortex, areas of the brain concerned with forward planning and regulatory control of emotional behaviour, continue to develop until the age of 20. In this article, I consider the significance of this extended postnatal developmental period for brain maturation and how brain evolution has encompassed certain biological changes and predispositions that, with our modern lifestyle, represent risk factors for well-being. An awareness of these sensitive phases in brain development is important in understanding how we might facilitate secure relationships and high self-esteem in our children. This will provide the firm foundations on which to develop meaningful lifestyles and relationships that are crucial to well-being.

Behavior↗
PubMed2004

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.

Adaptation, Physiological↗
PubMed2004

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.

Afferent Pathways↗
PubMed2004

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.

Animals↗
PubMed2002

Mammalian pheromones: from genes to behaviour.

Knocking-out selected genes for receptors of the vomeronasal organ has been found to impair specific aspects of pheromone-induced behaviour in the mouse. This is not unexpected; less predictable is the finding that deleting the gene for a vomeronasal-organ-specific ion channel causes gender blindness.

Aggression↗
PubMed2002

A possible role for imprinted genes in inbreeding avoidance and dispersal from the natal area in mice.

The expression of a subset of mammalian genes is subject to parent of origin effects (POE), most of which can be explained by genomic imprinting. Analysis of mutant animals has demonstrated that a number of imprinted genes influence brain development and behaviour. Here we provide evidence for POE on olfactory related behaviour and sensitivity to maternal odour cues. This was investigated by examining the odour preference behaviour of reciprocal cross F(1) mice made by embryo transfer to genetically unrelated foster parents. We determined that both adult males and females show an avoidance of female urinary odours of their genetic maternal but not paternal origin. This was found not to be due to any previous exposure to these odours or due to self-learning, but may be related to direct effects on the olfactory system, as reciprocal F(1) males show differential sensitivity to female odour cues. Currently the most robust theory to explain the evolution of imprinting is the conflict hypothesis that focuses on maternal resource allocation to the developing foetus. Kinship considerations are also likely to be important in the selection of imprinted genes and we discuss our findings within this context, suggesting that imprinted genes act directly on the olfactory system to promote post-weaning dispersal from the natal area.

Animals↗