Last week, Sci covered a paper on the nematode "version" of oxytocin, nematocin, and its role in learning behavior. We usually think of oxytocin-like peptides (including oxytocin and vasopressin), as being linked with emotion, trust, love, and of course, sex. But oxytocin also tends to get a lot of hype, especially as the "love"' or "trust" hormone. But it's not that. It's much more complicated than that. And understanding the evolution of oxytocin, and its very long history, allows us to understand HOW much more complicated than that.

Because while nematodes have an oxytocin-like molecule that has roles in learning behavior...well it also has roles in mating. But I wouldn't go do far as to call nematocin (oxytocin + nematode = nematocin!) the nematode love drug. Unless, of course, you believe nematodes have deep, passionate, trusting, and communicative one-night worm stands which commence upon immediate contact and end immediately after. Hey, you never know.

Garrison et al. "Oxytocin/Vasopressin-Related Peptides Have an Ancient Role in Reproductive Behavior" Science, 2012.

This happens to be an interesting issue of Science, in which TWO papers were published, both identifying nematocin, at the same time. As they both call the new molecule nematocin, I have hopes that the two groups were happily collaborating with each other to further the interests of science (though I know that many times, when two groups find the name new, hot thing, it's often a very bitter race to publish).


So what is nematocin? Nematocin appears to be a chemical closely related to oxytocin and vasopressin, those much vaunted chemical in mammals which are making so much press for their role in our emotions and moral behavior. But oxytocin and vasopressin are both more complicated than emotion. Vasopressin, for example, plays a role in water balance. And it appears that the newly discovered nematocin in the nematode C. elegans may be similar, with more than one role in more than one system.


The authors of this study were interested in particular in the role of nematocin in mating behavior. Oxytocin-like peptides are often involved in mating behaviors, but the degree to which its involved is up for debate. For example, giving oxytocin to, say, a vole, will drastically alter its mating behavior, facilitating things like pair bonding responses. But knocking out oxytocin produces much more subtle effects, which suggests that the effects on behavior may be more complicated.


And this complexity extends to worm behavior. The authors of this study first described nematocin (ntc-1) and its two putative receptors, nematocin receptor 1 (ntr-1) and nematocin receptor 2 (ntr-2). They then looked for the expression of nematocin and the nematocin receptors, to see if they were located in reproduction-related structures in C. elegans.



You can see above the expression of nematocin (panel A and B), and its receptors(all other panels), in the two different sexes of nematode. The first sex is male (top set of panels), and inseminates the other sex. The other sex (bottom panels) is hermaphroditic, and though capable of self-fertilizing, also receives sperm packets from males. You can see that in both sexes there is localization of the nematocin containing cells, as well as the nematocin receptor, on cells related to reproduction (remember, a chemical like nematocin can only act as long as there is a receptor present for it!). In the males the nematocin areas are localized to things like sperm-transfer and vulva sensing.


But how was it affecting reproduction? When the authors knocked out nematocin or its two receptors, there was no immediate effect on the worm. The animals were still viable and still produced offspring, but they did it at a much reduced rate. The authors looked at the mating behaviors of the nematode, and began to see why.



A nematode pair mates in stages. Upon first tail touch between nematodes (top panel A), the male presses up against the hermaphrodite. He then slides along and around the hermaphrodite (figures labeled 'backing', 'turning', and 'vulva search') until he fins the vulva (far right panel) and inserts his sperm packet.


And while the male nematocin and nematocin receptor knockouts COULD do all of these things, they weren't very good at them. They appeared less sensitive to the touch of another nematode, and when they finally responded, it took them a lot longer, and a lot more twisting and turning, to find the vulva. Restoring nematocin or the nematocin receptor brought the poor male's mating capacity back up to par.


Nematocin may serve another mating function as well. Male nematodes have a behavior where they leave a pile of bacteria (C. elegans dines on the finest of soil bacteria), and head out if there are no hermaphrodites present to mate with. But if you take out nematocin or its receptors, this behavior is suppressed, and the males stay where they are, further reducing their mating chances.


Unfortunately, so far it's hard to tell HOW exactly nematocin is having these behaviors. It appears to modulate, but not completely control, mating behavior in C. elegans (which echoes somewhat some of the mating effects of oxytocin in other organisms, modulatory but not full control). And it shows that the effects of oxytocin/nematocin are more than emotion, love, or morality. A chemical this conserved can wear many different functional hats, and in nematodes, it looks like there's one for lust, and one for learning.





Garrison JL, Macosko EZ, Bernstein S, Pokala N, Albrecht DR, & Bargmann CI (2012). Oxytocin/vasopressin-related peptides have an ancient role in reproductive behavior. Science (New York, N.Y.), 338 (6106), 540-3 PMID: 23112335