Love and Learn: "Nematocin", the nematode oxytocin

Nov 14 2012 Published by under Behavioral Neuro

Oxytocin always makes a lot of press. It plays roles in reproduction and mating behavior, social bonding, behavior related to morality. To call it "the love hormone" as some people like to do, is to grossly oversimplify the things that it does, something which can even be dangerous. And it also, in my opinion, really hides its light under a bushel. To call oxytocin "the love hormone" or "the trust hormone" is akin, in my opinion, to calling norepinephrine the "holy shit we're going to DIE" chemical. It covers up the complexity of function, and the deep and interesting evolutionary history that oxytocin has.

After all, as this paper shows, even nematodes have something like oxytocin. And in nematodes, "nematocin" isn't about a state of love and trust. Instead, it's about a state of learning.

Beets et al. "Vasopressin/Oxytocin-Related Signaling Regulates Gustatory Associative Learning in C. elegans" Science, 2012.

We know that oxytocin, vasopressin, and their chemical relatives go back a very long time, at least 700 million years. We know this because some invertebrates have analogues of these chemicals. And it's no wonder. Oxytocin and vasopression, types of neurohypophyseal peptides (short amino acid sequences), are important in behaviors like reproduction (oxytocin and vasopressin), and water balance (vasopressin). And they may also play a role in things like learning, especially in the nematode worm C. elegans.

C. elegans is a favorite in science. It lives in soil, and while it's elegantly simple, it shows some complex behaviors. And, as it turns out, it has its own version of oxytocin. Discovered by the authors in this paper and dubbed "nematocin" (get it? Nematode? Oxytocin? Nematocin? Well, I think it's cute), it's a small peptide that is very similar in structure to oxytocin. And like oxytocin, nematocin has specific receptors that respond to it, nematocin receptors 1 and 2 (ntr-1 and ntr-2).

Nematocin receptors are well-placed to place a role in C. elegans behavior

The top two panels show nematocin expression itself in C. elegans (linked to a "reporter gene" which expresses a green glowing protein), while the bottom two show the location of the receptors. In particular, the receptor is expressed in neurons which play important gustatory (that's taste) roles, as well as chemosensing. This suggested to the authors that nematocin itself might play a role in sensing chemicals in the worm's environment.

But when they first tested this (using a salt gradient, C. elegans is attracted to lower concentrations of salt, which signal the presence of food, and repulsed by higher concentrations of salt, which isn't good for their water balance), it looked like it was a no go. Worms that didn't have nematocin or the nematocin receptor still were able to tell the difference between high and low salt concentrations.

But what about something like learning? To look at this, the authors of this study tested gustatory learning in C. elegans. To do this, you expose them to salt (signaling the presence of food), but provide no food. The savvy worm will then ignore and avoid the signal when it is presented again. But when you knock out the nematocin or the nematocin receptor, this response is blunted:

You can see here the behavioral results. The naive worms will always head toward the salt source (white bars), but previously exposed worms (black bars on far left) avoid the signal, knowing there's no food there. But when you knockout the nematocin or the nematocin receptor, the response is blunted. The worms don't avoid (though they don't show the naive preference either), showing that nematocin helps chemosensory learning in C. elegans.

So far, it looks like this is more of a modulatory role than full control. When starved, nematocin didn't change the learning behavior, which the authors hypothesize is due to an over-ride of the system due to starvation. But it does show that oxytocin, or similar chemicals, go back a long way. And it shows that similar chemicals play more than one part, more than "love", or "pair bonding". In worms, nematocin may be about learning as well as love. And as for the love: stay tuned! Next week, we'll take another look at nematocin.

Beets I, Janssen T, Meelkop E, Temmerman L, Suetens N, Rademakers S, Jansen G, & Schoofs L (2012). Vasopressin/oxytocin-related signaling regulates gustatory associative learning in C. elegans. Science (New York, N.Y.), 338 (6106), 543-5 PMID: 23112336

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