At the cellular level, the layout of the nervous system in any given C. elegans specimen is much the same as any other: Every adult C. elegans has 302 neurons–arranged in the same pattern. Researchers from Mei Zhen’s lab in Toronto, Aravinthan Samuel’s lab in the Physics Department, and the Lichtman Lab in MCB wanted to know whether this similarity extends to individual synapses and teamed up to find out more.
They were also curious about how the worms’ connectomes—their neuronal connectivity pathways in aggregate—change as larval worms mature into adults. The results, recently published in Nature (PDF), reveal substantial variation from worm-to-worm but also indicate that few patterns are consistent across maturing C. elegans.
Led by postdoc Daniel Witvliet, who started the project as a graduate student in Zhen’s lab at University of Toronto and continued as a postdoc at Harvard, the scientists mapped every synapse in the connectomes of eight genetically identical C. elegans worms, which ranged in age from newly-hatched to adult. They found that the arrangement and anatomy of neurons was similar in all of the nematodes but that each individual had unique synapses.
They also found that the total number of synapses in the C. elegans connectome increases six-fold over the worm’s lifetime, from about 1,300 at birth to approximately 8,000 in adulthood. Only a quarter of the new synapses connected a neuron to a new synaptic partner cell; 74% of the synapses that developed during the worm’s maturation strengthened synaptic partnerships that existed at birth.
“Over maturation, the addition of synapses strengthened nearly all existing connections, and a substantial number of new connections were also formed between neurons that were not connected at birth,” says Witvliet. “We uncovered several biological principles that these connectivity changes followed, from the level of individual neurons to the level of the entire brain.”
The team also noticed that interneurons, which receive signals from sensory neurons and send signals to motor neurons, changed much less than sensory and motor neurons did. The team suspect that these interneurons, which are part of the nematode’s central decision-making circuitry, have a robust ability to accommodate alterations in sensory input and motor output and hence change only slightly as the animal matures.
“Central decision-making circuitry was relatively unaffected by maturation whereas the more peripherally located sensory and motor pathways remodeled extensively,” says MCB faculty and study co-author Jeff Lichtman. “It was also evident that the network became progressively more modularized into functional and structural subunits over development. Therefore, comparisons between the connectomes of individual animals seems to be a productive way to reveal principles that underlie brain maturation.”
In the paper, the researchers boil down their findings into six general principles that likely govern nervous system maturation across C. elegans. “One such principle is that the outputs from the same neuron maintain their relative strengths, while input connections that converge on the same neuron tends to become more heterogeneous,” Witvliet says. “Thus, it appears that each cell regulates the strengthening of its own outputs but does not dictate the relative strengthening of its inputs.”
Although they found considerable variation between individual nematodes, the authors conclude that conducting complete synaptic censuses in multiple genetically identical individuals is a fruitful way to investigate nervous system development. They add that connectomic efforts like these can only be accomplished through collaboration between multiple labs.
The project’s online connectome database can be perused at NemaNode.org.