If you want to get hitched for life, you have to make the right moves from the start. For example, prairie voles (Microtus ochrogaster) form lasting pair-bonds that are initiated when a female displays special interest – known as partner preference – in a male. For the female to form her partner preference she releases two hormones, oxytocin and vasopressin, that bind to their receptors in the pleasure and reward centre of the brain – the nucleus accumbens. An increase in the expression of oxytocin and vasopressin receptors in the nucleus accumbens helps to kindle a female's affection toward a male, but how their expression is regulated is not known. One method of increasing gene expression is to change the way in which DNA is packaged around the region of the gene that regulates gene expression – a process known as epigenetics. Histone acetylation is a type of epigenetics that unlocks the tight DNA spiral to help activate key genes. This effect can be reversed by deacetylating the histones to deactivate genes. Postdoctoral researcher Hui Wang and a team of neuroscientists at Florida State University, USA, set about testing whether epigenetics are involved in partner preference formation in female prairie voles.
Using a drug that promotes gene activation by preventing histone deacetylation – called trichostatin A (TSA) – Wang and colleagues injected the drug into the brains of female voles and then housed each female with a male for 6 h to find out how TSA affected the female's partner preference. Normally, a female will not develop a preference for a male over such a short period of time. However, Wang and colleagues found that injected females did favour their partner male over a stranger – indicating that blocking histone deacetylation and increasing histone acetylation permitted the females to form a partner preference.
Wang and colleagues then measured changes in gene and protein expression of the oxytocin and vasopressin receptors, as well as the amount of histone acetylation in the regulatory regions of these two genes. They found that the TSA-injected females had an increase in oxytocin and vasopressin receptor expression in the nucleus accumbens, likely driven by a measured increase in histone acetylation in the regions of those genes that regulate their expression.
Next, the team injected new females with TSA but this time they also injected some of these females with additional drugs, one of which blocked the oxytocin receptor and the other the vasopressin receptor, to find out whether this would prevent partner preference formation induced by TSA. They found that females given TSA in combination with either of the receptor blockers did not favour their partner male over a stranger, meaning that partner preference was not formed.
Having used TSA and other drugs to show that the expression of the oxytocin and vasopressin receptors in the brain could be epigenetically regulated, Wang and colleagues decided to find out whether the animals use this epigenetic mechanism in practice. To do this, the team housed a new set of uninjected females individually with a male for 24 h and then measured the gene and protein expression of oxytocin and vasopressin receptors in the females' brains, and the amount of histone acetylation in the genes' regulatory regions. They found that the expression of oxytocin and vasopressin receptors in the nucleus accumbens increased, and that the activation of these two genes is achieved by histone acetylation. So, Wang and colleagues have shown that partner preference is epigenetically driven in the pleasure and reward center of the brain in female prairie voles, improving our understanding of the neurobiology of social affiliation as well as possibly unearthing the secret behind Cupid's magic arrows!
