When scientists seemed to have completed the map of the nervous system of a tiny male worm in 2012 (T. A. Jarrell et al. Science 337, 437–444; 2012), some researchers were already questioning whether the whole effort, originating some 40 years before, was truly worth it. The construction of the wiring diagram for the nervous system of the male of the nematode species Caenorhabditis elegans built on the wiring diagram for the hermaphrodite, established more than 25 years earlier, and required painstaking tracing of how the male worm’s extra neurons connected to each other.
Stephen Hawking was talking metaphorically when he famously wrote that to unravel the laws of nature would be to know the mind of God. The C. elegans project was quite literal: as Sydney Brenner, the originator of the project, jokingly entitled the manuscript of a landmark 1986 paper, the scientists really did want to know ‘the mind of the worm’. And in doing so, they argued, they could learn more about how brains create behaviour in higher organisms all the way up to humans.
Can we really know the mind of a worm? Three years on we have an answer of sorts: possibly. In fact, it turns out that we did not even find all the neurons that comprise the male worm’s mind. For on page 385, researchers including two of the 2012 team publish an appendix to the wiring diagram of the male C. elegans. As well as the 383 neurons already identified, they describe the discovery of neurons number 384 and 385, which they found in the worm’s head.
There is much to admire about the new work, not least that the researchers chose to call the new cells — mystery cells found in the male worms — MCMs. No metaphor there either. It stands for mystery cells of the male.
What’s on a male nematode’s MCMs? Not so much of a mystery as it turns out: sex. The new neurons have an old role, and help the worms to learn to prioritize the search for a mate over the need for food. When these neurons are put out of action, the male worms never discover the facts of life. The findings offer much more than a completion of the neural map of the male worm. In most organisms, sex-specific differences in behaviour extend to cognitive-like processes such as learning, which can aid reproductive success, but the underlying neural mechanisms are mostly unclear.
The discovery of the MCMs, and the subsequent experiments with them, link developmental and anatomical sex differences in high-order processing areas of the brain to sex-specific behaviour during learning. In doing so, they help to shed light on the neural basis of sex differences in behaviour. And they show that these neurons arise upon sexual maturation from specialized cells called glia — unlike other neurons in C. elegans and other invertebrates, which arise from epithelial or undifferentiated blast cells.
Was the effort to trace out the connections between the male nematode’s neurons worth it? Like all good maps, the wiring diagram of the C. elegansis best viewed as a starting point. The final destination is sure to surprise us.