Gal Science: The Virgin Brain -The Toast

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As The Toast searches for its one true Gal Scientist, we will be running a ton of wonderful one-off pieces by female scientists of all shapes and sizes and fields and education levels, which we are sure you will enjoy. They’ll live here, so you can always find them. Most recently: Stop Being Terrified of Chemicals.

Some people consider losing one’s V-card to be a huge life-changing deal, while others find it anticlimactic (and a social construct.) Regardless of your experience, however, you have probably not stopped to wonder whether losing your virginity changes the genetic expression in your brain. Lucky for you, some scientists do wonder about these things.

It would be pretty difficult and probably unethical to conduct human studies on virginity (I mean would you be willing to lose your virginity in a lab, FOR SCIENCE?), so scientists have turned towards our adorable friends from the prairie.

volelove.png

The prairie vole is one of the few mammals that mates for life. This has been known for a while, but they have recently exploded in scientific popularity. The promise of finally being able to scientifically study LOVE has intrigued both scientists and the press. A recent study by Wang et al. (yep.) investigates what happens to the DNA in the brains of prairie voles when they undergo “mating based pair bonding.”

What is mating based pair bonding? Well, basically, the scientists take virgin female prairie voles and put them in a cage with a sexually experienced male prairie vole for 6 hours. The voles either have sex during that time or they don’t (there is video evidence.) If they have sex, the female starts to bond to the male and prefers him over a stranger (this is measured by essentially testing how much time she spends cuddling him at a later time.) But if they don’t have sex, the female shows no preference for him. (Side note: If the female vole spends 24 hours with the male without sex, a preference will ultimately develop as shown by Williams et al. 1992.) So, basically, either sex or time seals the deal.

Wang and others wanted to know what happens in the brain during the sexual 6-hour bonding process. Having sex releases two important neurotransmitters in the brain, oxytocin and dopamine. These neurotransmitters only work when they activate the oxytocin or dopamine receptors. The cell makes these receptors from its own DNA. Dopamine receptors are diverse and complicated, so we’ll focus on the oxytocin receptors for now. In humans, oxytocin is generally thought to increase “trust.” In the prairie vole, oxytocin receptors are particularly important in the development of the pair bond. The monogamous prairie voles have very dense oxytocin receptors, while their close (but non-monogamous) cousins, the montane voles, have fewer oxytocin receptors. It’s even been shown that artificially increasing the oxytocin receptors in female voles makes it easier for her to develop a preference for a male partner. In the study published in Nature Neuroscience, Wang et al. manipulate the density of oxytocin receptors in the brains of the female prairie voles by messing with their DNA. Specifically they epigenetically modulated which pieces of DNA were available for turning into useful things (like, say, oxytocin receptors), and which were not available.

You probably know from biology class that each cell in your body contains a complete copy of your DNA. But a skin cell is not the same as a heart cell or a bone cell or a brain cell. And brain cells are not all alike either. Epigenetics is basically a way to control which sections of DNA each cell has access to by regulating how loosely the sections of DNA are wound up. If you loosen up a section of DNA (acetylation) your cell has better access to it and you get a lot of that gene expressed (and that receptor produced). If you tighten up a section of DNA (methylation), you prevent that section of DNA from being expressed.

Wang et al. used a histone de-acetylase (HDAC) inhibitor to keep the section of DNA that codes for the oxytocin receptor acetylated (loosened), so more oxytocin receptors would be created. The virgin prairie voles who got the HDAC inhibitor indeed had more oxytocin receptors in certain parts of  their brains. But the amazing thing is they didn’t need to have sex with their 6 hour male buddy to develop a preference for him! The DNA manipulation was enough to replace the important sex component of the experiment.

This result is interesting and everything, but it doesn’t actually tell us that sex changes the brain. So far Wang et al. have just shown that you can eliminate the need for sex by epigenetically increasing oxytocin receptors. But, of course what we all really want to know is: does sex change the brain?

Wang et al. wanted to know the same thing, so they did one final experiment. They measured the amount of acetylation on the oxytocin receptor part of the DNA in virgin voles and paired, sexed voles. And not too surprisingly, the female voles who had had sex had more acetylation on the oxytocin receptor part of their DNA and consequently more oxytocin receptors. Having sex changed their brains.

Like most experiments, this one leaves us with many questions. What exactly is it about the sex that causes the brain change? If you could pop that prairie vole cherry by artificial means, would you get the same oxytocin receptor changes? My guess is no, but we won’t know unless someone does that experiment. Similarly, is the virginity of these voles important? Would these experiments have the same result if the female voles were sexually experienced?

Alternatively, is sex sufficient to cause partner preference and the reported brain changes? The 6 hours that the voles spent together might be critical for the increase in oxytocin receptors. One experiment that Wang et al. did not do was put the voles together for a short time (just an hour or so) and allow sex to occur. If these ‘sex-only’ voles had the same brain changes, this would mean that the increase in oxytocin receptors was due to sex specifically. If they did not have the same brain changes, it would mean that the increase in oxytocin receptors was due to the bonding process as a whole.

Of course this has limited applications to human relationships. We don’t get put in a room with a potential mate for 6 hours and then get tested on how much we cuddle hir later. We can’t look at the data and say “Yep, I’m totally bonded to that person.” Even something that seems straight forward like ‘sex’ is not well defined for us. Does any type of sexual experience count here?

But let’s speculate wildly about what this means for us anyway. If we ignore the above caveats and assume that ‘sex’ causes more oxytocin receptors to be created in the human brain, does this change what sex means?  Should we protect our virginity like Jane Austen characters, lest we accidentally ‘fall in love’ with a sex-buddy when we don’t want to? That’s obviously extreme, and only your own experience will tell you how much ‘preference’ you have for someone after sex. If anything, the study simply suggests that sex can change the brain in a way that helps build a partner bond.

Wang, H., Duclot, F., Liu, Y., Wang, Z., Kabbaj, M., 2013. Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles. Nat. Neurosci. 16, 919–924.

Rebekah Evans has a Ph.D. in neuroscience and is a research fellow at the National Institutes of Health. She is currently conducting experiments to figure out how dopamine neurons integrate information. She blogs about how amazing neurons and other cells are at Cellularscale.blogspot.com and tweets @cellularscale.

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Sounds like cuddling might be the real danger, which I already knew.
2 replies · active 566 weeks ago
"10 Ways You Won't Believe Cuddling Can Kill You"
Easy there, Buzzfeed/Cracked/Nancy Grace (I can't tell how alarmed a tone it was written in)
"The virgin prairie voles who got the HDAC inhibitor indeed had more oxytocin receptors in certain parts of their brains. But the amazing thing is they didn’t need to have sex with their 6 hour male buddy to develop a preference for him! The DNA manipulation was enough to replace the important sex component of the experiment."
So, not quite the same as sciencing up sexual attachment. More like creating a prairie dog who wants to move in on the second date. Normal variations in oxytocin receptor density (or some equivalent) probably play a role in how quickly different people get attached.

I find all this "mind as tangible machinery" stuff fascinating. And creepy.
1 reply · active 565 weeks ago
Haha. It really is more of a 'second date' sort of preference here.
One thing that would like to know is does 'bonding' to one male vole prevent or weaken the female's ability to bond to another? For the male voles bonding to the females it seems to work that way. A brain change after bonding/sex seems to reduce the male's chance of bonding to another female even if her has sex with her. Of course that is a topic for another whole article.
I just really think that picture of the voles with the heart is the cutest thing.

(And this was great and fascinating!)
Great article! My question is; have they done experiments to see how much time is the minimal time needed for a virgin female vole to bond with a male vole without sex. I saw the one hour designation but I wasn't sure if that was a minimal time that had been tested or simply a known time it could take.
2 replies · active 565 weeks ago
Great question. Sorry for taking so long to answer comments, I was in a dark room shooting lasers at neurons.
I don't think anyone has tested to see the minimum amount of time needed for a bond to form. In this article it was either 6 hours + sex or 24 hours without.
In a future life, I hope to have an excuse as cool as "I was in a dark room shooting lasers at neurons."
I loved this article! Genetics & behavior are two of my favorite things to study and I'm basically just grinning like a fool at my computer right now.

Thanks!
(I mean would you be willing to lose your virginity in a lab, FOR SCIENCE?)

Where was this question when I was in high school? :(
Hoo boy. I feel like I'm in trouble just for clicking on this article.

But I don't even want to wait him out. I'd settle for not being a bad friend just because I'm not also in love with him… (cuz, ya know, different strokes)
I'm in all kinds of experimental head space now! This is so interesting.

Here's some things I wanna know:
* Is the acetylation on the oxytocin receptor math similar on other critters who don't mate for life - virgins have less no matter which type of vole you are?
* If so, I wonder if the intensity of how ramped up the receptors are changes if you're a monogamous or non-monogamous critter - do players get oxy but true-hearts get even more / steadier amounts?
* Also curious how these levels work in social vs. non-social animals; do family groups who spend their time in cuddle piles but not necess having sex have higher oxy levels?

(I know those aren't experiments that were done here, I'm just spitballing.)
1 reply · active 565 weeks ago
1. Interesting question. I don't think it is known yet whether other (non-pairing) animals have this same brain change due to sex. Actually it is not clear from this study how long this change lasts. It might not be permanent.
2. Also not known, but it would be interesting to see how variable the brain changes and the 'strength' of the pair bond is between voles. Do some voles pair more easily than others, are there specific pairings that work out best (Vole soulmates?)
3. Cuddling can definitely increase oxytocin levels (mothers breastfeeding is an example), so it wouldn't be too surprising if cuddly animal families (bunnies or grooming monkeys, for example) had different oxytocin receptor patterns in their brains. I've even wondered if colder climates facilitate pair bonding because you are more likely to be cuddled up with someone for an extended period of time. (Go to Alaska for a honeymoon, not Aruba). I have absolutely no data for this, it's just a possibility that has crossed my mind.
So fascinating. I have a friend who, for a while, refused to devirginize girls, because "they always get so clingy!" I called him a pig, and told him to stop being a jerk about that, but apparently he may have been right.
1 reply · active 565 weeks ago
Well ... he was right *if* he was dating prairie voles.

And if he was dating prairie voles, I feel like you're gonna have to have a conversation with that dude.
Ugh, why'd they only test virgin female voles? What about male ones??
Haha I am THAT PERSON.
2 replies · active 565 weeks ago
Actually there is a lot of research on the neurochemistry of male prairie voles during the bonding process. Just not in this study.
Good! Because that kinda bugged me too. :)
I know sex changes MY brain, for sure. Lack of sex after a few days results in my being irritable, clumsy, and absent-minded. I don't think that's the sort of thing this study was trying to test, though.
Sorry, but the research described here does not suggest that sex per se changes the brain. Just that the paired-off voles have higher oxytocin levels than the unpaired ones, and that you can artificially induce pair-bonded cuddliness by artificially increasing the prairie voles' oxytocin levels. Oxytocin is nicknamed the 'cuddle hormone' so this isn't surprising. Those prairie voles are adorable though.
1 reply · active 565 weeks ago
Yes it is not just the sex that changes the brain, that's true.

But the change is in oxytocin receptor expression in the neurons. It's more than just "there is a lot of oxytocin in the brain" it is that the brain is in a state where it can "sense" oxytocin better.
But if prairie voles mate for life and they were using sexually experienced male voles, does that mean they were recently widowed? Or do they mate for life with a "if you can't be with the one you love, love the one you're with" clause?
1 reply · active 564 weeks ago
Since they weren't studying the male voles in this case, it didn't really matter if the guys were previously bonded to other females. Already bonded males will often still have sex with a passing female who is not his true mate. But he won't bond to her, because his brain was changed by his first bonding process. (and not just the oxytocin receptors either, but that's a topic for another post)

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