First up on this last morning at SFN2010 is Larry Young from Emory who will be discussing the Neurobiology of Social Bonding and Monogamy: Implications for Autism Spectrum Disorders. To start out the talk, Young discusses examples of pair bonding and monogamy in the animal kingdom. First, some jokes regarding human monogamy, which went by two fast for me to type down. These are followed by a brief mention of prairie vole pair bonding, to which Young will return multiple times during the course of the talk. And finally, a more exotic example: monogamy in the deep sea. The deep sea angler fish live deep in oceans, and displays a rather extreme form of pair bonding. To quote Larry Young*, “a male can spend half of his lifetime searching for a female. So when the male finds the female, he forms a bond. And not an emotional bond. A physical bond.” These extreme changes in the male’s circumstances ensure that the male WILL reproduce every time the female spawns.
Did pair bonding evolve by tweaking mechanisms that promote maternal bonding? Pair bonding has evolved multiple times, and it seems unlikely that such behavior would have evolved newly each time. So the hypothesis is that pair bonding is a tweaking of the maternal bond that is evident in many (if not all) mammals. It is known that the chemical oxytocin is highly involved in regulating the peripheral physiology of reproduction, as well as the transition to maternal behavior following successful reproduction.
An example: virgin rats avoid pups, but a day before they give birth, there is a behavioral change in that pregnant rat will start to seek out pups. Oxytocin is critical for this behavioral switch – injection of oxytocin into virgin rats will cause them to seek out pups. The same is true for sheep and bonding with lambs (except with oxytocin release stimulated via cervicovaginal stimulation of the female sheep).
And so back to pair bonding in voles. The basic behavioral assay is called the Partner Preference Test, details of this assay can be found in the literature, but, in brief, involves allowing a female and male to mate, and then presenting the male with a novel female and its mating partner. The male will spend the vast majority of its time with its mating partner, and will in fact display aggressive behavior towards the novel female. [Bloggers note: video of the pair bonded voles clearly demonstrates the complete adorability of social interactions between pair bonded animals.] Oxytocin is required for female pair bonding.
And now we move onto the prairie vole versus meadow vole story. I highly recommend reading the original papers, but the basic gist of the research is that prairie voles display social pair bonding while meadow voles do not.
Oxytocin release into nucleus accumbens causes pair bonding. It makes sense that there is a conserved oxytocin mechanism underlying both pair bonding and maternal bonding. Think back to the research showing that in female sheep, cervicovaginal stimulation (which simulates birthing) releases oxytocin and results in maternal bonding. This mechanism of oxytocin release could easily also underlie pair bonding because, to quote, “there is a heck of a lot of cervicovagina stimulation going on when females are mating with males.”
So female bonding involves release of oxytocin, but what about male pair bonding. Vasopressin plays an important role in pair bonding in male prairie voles (also underlying territorial behavior, scent marking, and aggression). A bit of wild speculation – female pair bonding may have evolved from the maternal bond mechanisms, whereas perhaps male pair bonding evolved from the territorial processes. Another great quote (paraphrase, really): “So male voles consider females to be part of their territory. I’m only talking about prairie voles here.” Animals without of oxytocin and vasopressin have social amnesia.
Other molecules required for partner preference include dopamine and opiates, which suggests a link between mating and the classical reward circuitry in the brain. How does mating activate the reward system? During mating, the sensory stimuli activate the VTA causing release of dopamine/opiates into reward areas of the brain. Experimental evidence of a link between sex and reward learning: “we know that a male rat will press a lever to get a female rat to drop out of the ceiling”.
Why do meadow voles not form pair bonding? Interestingly, there is a lack of vasopressin receptors in the ventral pallidum in meadow voles, but not in prairie voles. Expressing vasopressin receptors in this area in meadow voles causes all of the “transgenic” voles to form pair bonding. Looking at the genetic mechanisms underlying the difference in vasopressin receptor expression, they first looked at differences between species (see previously published work for this story), but then ended up looking at individual variation within the avpr1a gene (vasopressin receptor) within the prairie voles. Interestingly, variation in the length of the microsatellite associated with the avpr1a gene can predict how likely the animal is to form a pair bond. Males with short microsatellite sequences are less likely to form a pair bond than males with long microsatellite sequences.
Is the work in voles applicable to humans? Another great quote (again, probably a paraphrase) “I work at a medical school, so I’m always asked, ‘Well these prairie voles are cute and everything, but how can we use…profit… off of this’”. Several groups are looking at human pair bonding, as well as levels of oxytocin and vasopressin in humans. On example is a recent paper that showed that genetic variations in the vasopressin receptor (again, avpr1a) predict whether human males will report a crisis in their marriage. (Bloggers note: commentary from the grad student sitting next to me: “All right, I’m getting a spit test.”). Further studies regarding the role of oxytocin in human relationships involve giving humans oxytocin, and how shown that this treatment can: improve “mind-reading” in humans, improve the likelihood of eye contact between partners, increase emotional empathy and enhance socially reinforced learning. From these studies came the hypothesis is that oxytocin is acting by increasing the social saliency of the task stimuli, and this hypothesis brings us to the topic of autism. Autism spectrum disorder is characterized by a deficit in social interactions. Current strategies for enhancing oxytocin function involve identifying novel drug targets for promoting endogenous oxytocin release. One identified drug is melanotan II, which is also used in tanning and erectile dysfunction. Importantly, meadow voles that are given melanotan II form pair bonds, most likely because the drug stimulates endogenous release of oxytocin. This research has suggested that meadow voles might be a useful model for screening drugs for enhancing social cognition – this possibility is being explored, alongside work to develop primate models that could be used to test any drugs identified in the vole model as possibly enhancing social cognition.
And finally, a plug for Emory Universities new center for translational work.
*I have attempted to quote verbatim from Larry Young's talk. All attempts to do so are indicated by quotations. However, given discrepancies in speed of his speech versus my typing, some quotations may not be exact.