August 6, 2012 | 1
Our brains are made of millions of neurons. Tons. A lot. We scientists spend a lot of time studying those neurons, how they function individually, and how they respond to outside stimulation.
But neurons cannot function alone. What sets a neuron apart is its ability to carry electric signals and to transfer chemical signals to other neurons. The function of neurons is not in the neurons themselves, it is in the connection between them. And this incredibly complicated network, composed of billions of connections, is called the connectome.
If we knew the connectome of the human, we’d know a lot more about the brain than we do now. We are learning it, little by little, but with a series of connections that are so incredibly vast, it’s just too much right now to examine every single possible connection. Right now the only way to ensure getting every single connection in painstaking detail is to use electron microscopy to view synapses, the connections between neurons. Concentrations of the little organelles which signify a synapse (such as vesicles full of neurotransmitter), can tell you where each connection is placed. But the electron microscope can only look at a very small section at a time, making the mapping of a connectome an incredibly arduous task.
And this is where the worm comes in.
Jarrell et al. “The connectome of a decision-making neural network” Science, 2012.
C. elegans, to be exact. The nematode is a darling of basic research, and for a very good reason. C. elegans is incredibly simple, having exactly 302 neurons in the entire body. Well, 302, or 383. There are two kinds of C. elegans, hermaphrodite and male (there are no females). The males mate with the hermaphrodites. But this means that the male C. elegans is slightly different from the hermaphrodite C. elegans. While the hermaphrodite has 302 neurons, the male has 383. And most of these appear to be devoted to a complex series of behaviors characteristic of mating.
The connectome of the C. elegans hermaphrodite has already been mapped out, but the male has not. Until now. The authors of this study, conducted at the Albert Einstein College of Medicine, looked at the connectome of the C. elegans male, focusing on the posterior half of the nematode, the circuits that govern mating behavior.
And the mating of C. elegans is more complicated than you might assume.
Here you can see the C. elegans mating system. When a male bumps into a hermaphrodite, it begins seeking along the prospective mate’s body, searching for the vulva. It slides itself along the body, sometimes having to turn back and search again. When it finds the vulva, it reaches out a prod from its anal region toward the vulva. It then inserts a spicule, a thin hollow spine, and uses that it eject sperm into the vulva. Then it withdraws and makes its escape.
They have to do it quickly, because often the hermaphrodites aren’t having any. After all, they can fertilize themselves perfectly well, thanks, what do they need with any old male? Often the hermaphrodites are either uncooperative or actively trying to get away. The set of behaviors thus needs to happen very fast.
To look at how this happens, the authors of this study looked at the posterior half of the C. elegans. This area has 170 neurons (81 of which are male specific) and 64 muscles (40 of which are male specific). The vast majority of the 170 neurons (144 of them) end on sensory organs that are directly related to mating.
Using a combination of electron microscopy and computer programming (to look at the different types of connections and predict short or long distance communication from them), the authors were able to form a map of all the neural connections of the mating circuitry.
Here you can see all the muscles and gonad that have to be controlled in mating, and where the neurons impinge on them, creating a rough map of the connectome in this area. The top panel (click to embiggen) has the big muscles that control the bend of the body as the male searches along the body of the hermaphrodite. The second panel is the muscle series that controls the opening of the cloaca (the all purpose exit hole that worms have instead of an anus) and the release of the spicule used during insemination. The three middle panels are response modules, showing the neuronal connections on to muscles, which respond to where the male senses he is relative to the hermaphrodite, and how he needs to move to get correctly positioned. The final panel is the insemination module, showing where the connections are between the neurons and the insemination muscles and gonad.
So that’s the anatomy of the connections. But anatomy of connections is nothing without knowledge of where the information is going. This is where the computing part of this project came in, as the authors figured out how many connections went where, and how strong or weak they were. And they came up with this:
This is the hypothetical information flow through the network, with the number of synapses and where they are going. It’s even more complicated than what is seen here, the connections create a series of feed-forward loops to keep the male’s mating behavior pattern running until he finds the vulva, and then to feed forward to get the sperm into the partner, and to allow it all to happen as quickly as possible.
The knowledge that a connectome like this can give us is really fascinating. Further study with connectome’s like these can give us more detailed insight into how an animal functions and performs seemingly complex movements, the neurons contribute to the multiple steps during mating. Not only that, knowing the final connectome means that we can begin to explore it during development, discovering how cells become specific neurons making highly specific connections to achieve a final function. And that’s a lot of information and possibilities to glean from worm sex.
Jarrell TA, Wang Y, Bloniarz AE, Brittin CA, Xu M, Thomson JN, Albertson DG, Hall DH, & Emmons SW (2012). The connectome of a decision-making neural network. Science (New York, N.Y.), 337 (6093), 437-44 PMID: 22837521
NOTE: I edited this post to add in the author’s institution and correct a point on mating. Namely, the idea that there are “hooks” used to hold the female. The hooks do exist, but I have been informed that their use has not been determined.