Researcher in the Spotlight February 2015

Prof Gareth Leng is head of the Integrative Centre of Physiology at the University of Edinburgh. He uses a multidisciplinary research approach, including electrophysiology, molecular neuroanatomy, behavioural and functional studies, and computational modelling. His research focuses on understanding neuronal networks in the hypothalamus, particularly those controlling pituitary hormone secretion and those controlling appetite and obesity.

What is you research about?

I’m interested in how the hypothalamus regulates physiological processes. My research has embraced many different systems in the hypothalamus -including the networks that control growth hormone secretion and those that regulate appetite, but I began by studying the neurons that secrete vasopressin and oxytocin from the pituitary gland.

How did you come to be working on this topic/in this field?

By accident. My first degree was in mathematics, and I thought that it could be interesting to apply this to neuroscience, but I didn’t know much about the brain. So I did an MSc in Birmingham on “Neurocommunications” and stayed there to do a PhD in auditory physiology. Immediately after that, Barry Cross, the Director of the Babraham Institute in Cambridge, recruited me to his research group in Neuroendocrinology. I don’t think I even knew what a hormone was – but Barry Cross didn’t care: he gave me a lab, and told me to do something interesting- he didn’t care what, as long as it was about neuroendocrinology.

You have done some research about love and monogamy. What happens when we fall in love?

I’ve never done any research on love or monogamy. For me, those aren’t particularly interesting questions – we don’t know enough to see the shape of what I would think of as real explanations of these things. My research is on how oxytocin release is regulated in the brain, and how this affects other neurones. Of course I’m interested in the sort of things that might help to understand how oxytocin might change behaviour. This is a big challenge, because we need to find a way of understanding how a brief exposure to this hormone alters neuronal network properties for a very long time, and in a way that makes them behave in new but meaningful ways. It seems as though oxytocin can “reprogramme” brain networks – or redirect networks from working in one mode to working in a different mode. I’ve been fortunate enough to find some things that seem to help us understand how this might happen, and if this is what happens in our brains when we fall in love, well maybe what I do might help to understand that one day.

Can only humans fall in love?

If we think of love as comprising lust, sexual attraction and long term attachment, then most birds, many fish, some reptiles and amphibians, but just 3% of mammalian species fall in love.

How do we know that oxytocin is responsible for this bond?

Oxytocin, or a molecule so closely related to oxytocin that it is effectively identical, is present in all vertebrate species. Indeed a very closely related molecule is present in most if not all invertebrates too. Oxytocin (or its close relative) is involved in processes that are integral to reproduction – generally in many different aspects of reproduction, depending upon the species concerned. In prairie voles, one of the few monogamous species of mammal, a female bonds with a male when oxytocin is released into her brain in large amounts during sex. A bond can be formed without sex if oxytocin is given into the brain of a female vole in the presence of a male- and if an oxytocin antagonist is given instead, then sex does not produce the same bond.

Why is the mountain vole promiscuous but the prairie vole monogamous?

They both have plenty of oxytocin, but the key difference is in where the oxytocin acts. These two species have oxytocin receptors in different brain regions.

Are there also differences in humans? Do men and women fall differently in love (have different numbers of receptors), and can this also differ between individuals?

A successful bond involves the male as well as the female, and what happens in his brain is a bit different to what happens in hers. In males, often the sign that a bond is formed is in the expression of aggression towards other males. What we might call jealousy perhaps. This seems to be linked to the release in the brain of vasopressin – a different but closely related molecule. Again, differences between species reflect differences in where receptors for vasopressin are expressed in the brain. In fact, we can look at differences between species in the genes for vasopressin receptors, and these differences predict whether a species is monogamous or promiscuous. So what about humans? Well the vasopressin receptor gene in humans is one of the most variable parts of our genome – so different individuals have slightly different versions of this gene. Intriguingly, these differences seem to correlate with relationship success in men.

What effect does oxytocin have on men and women?

In women, oxytocin is essential for lactation. Without oxytocin, suckling will not produce milk let-down at the breast. It is released during childbirth, and without it, labour can be difficult and prolonged. It is released during sex: in men, it facilitates penile erection and ejaculation, and in women it facilitates sperm transport up the reproductive tract to increase the likelihood of fertilisation. But it also has many other effects- on the heart, pituitary gland, gastrointestinal tract, and even on bone. In the brain? We don’t know. We don’t have any direct way of measuring oxytocin release in brain regions in the human. There have been lots of studies involving squirting oxytocin into the nose in huge, huge amounts, in the hope that some might get into the brain. It seems like wishful thinking to me- the brain is very well protected to prevent oxytocin getting in from outside, but the amounts given are so huge that maybe a bit gets in. But it seems more likely to me that the effects observed in these studies reflect the indirect consequences of actions of oxytocin at the periphery – on the penis, the heart, the gut and elsewhere. These studies don’t control for the peripheral effects of the hormone, they don’t give any evidence that any of the oxytocin given into the nose actually enters the brain in the relevant time frame, and mostly they are best filed in the wastepaper basket.

Oxytocin, vasopressin and autism – is there a connection?

Mice that lack oxytocin show some subtle defects in social behaviour – they aren’t good at telling the difference between familiar and unfamiliar individuals. So there’s a lot of interest in whether defects in oxytocin signalling may contribute to autism – and even if they don’t in whether supplementing oxytocin in the brain might ameliorate the social deficits of autism. It’s a mixed picture so far though. The most rigorous study of oxytocin and autism so far has shown that there is no lack of oxytocin in autistic children. There have been cases where autistic individuals have been shown to have a mutation in the oxytocin receptor – but these are very rare, and it’s not known whether similar mutations occur also in non-autistic individuals. Intranasal application, on the best study so far, is ineffective, unsurprisingly in my view. It’s too early to let go of this idea completely – but we need a breakthrough. Specifically, we need to find a molecule that acts like oxytocin but which we can get into the brain – a molecule that can cross the blood-brain barrier which is something that oxytocin can’t do. Either that, or we need to find a way of boosting the release of oxytocin within the brain.