To date, scientists have created complete connectomes—maps of all the neural connections in the brain—for only three organisms with just a few hundred brain cells each.1-3 Now, with a study published in Science, the mighty Drosophila larva joins the ring as the heavy-weight with the largest 3-D whole brain reconstruction to date.4  

Mapping the fruit fly larva connectome was no easy feat. It required a transatlantic tour de force. Marta Zlatic, a neuroscientist at the University of Cambridge and coauthor of the study, previously collected thousands of high-resolution images of a Drosophila larva’s brain cells and their connections using volume electron microscopy.5 However, researchers had only partially reassembled these images before now.   

Imaging is no longer the rate limiting steps with these small brains. 

—Marta Zlatic, University of Cambridge

To speed up this painstaking process, Zlatic’s team developed computer-assisted reconstruction software.4 After many hours spent aligning and stitching together the remaining neural connections, the team was rewarded with the largest synaptic-resolution connectome to date, which included 3,016 neurons and 548,000 synapses. 

To explore this rich synaptic wiring map, Zlatic and her team developed novel computational tools that characterized neurons based on connectivity profiles and predicted behavioral roles for these circuits. These efforts revealed novel circuit motifs, or connectivity patterns, and circuit hubs, many of which are involved in learning processes. 

 

Marta Zlatic and her colleagues created a 3-D reconstruction of more than 3000 neurons and their connections in the fruit fly larva brain.
Johns Hopkins University, University of Cambridge

Although this connectome project was years in the making, Zlatic said that their reconstruction software in combination with advancements in volume electron microscopy will greatly facilitate experimental connectomics. “Imaging is no longer the rate limiting step with these small brains,” said Zlatic. What previously took them a year to image now only takes weeks.

Harald Hess, a microscopist at the Howard Hughes Medical Institute’s Janelia Research Campus who was not involved in the study, noted that connectomics efforts have been key to advancing volume electron microscopy technologies. “It's really cool right now with the drive in the connectomics field to really access larger volumes,” said Hess. “It makes other non-neuroscience applications more achievable and accessible.”

References

  1. White JG, et al. Phil Trans R Soc B. 1986;314:1-340.
  2. Ryan K, et al. eLife. 2016:5:353-356.
  3. Verasztó C, et al. bioRxiv. 2020;2020-08.
  4. Winding M, et al. Science. 2023;379:eadd9330.
  5. Ohyama T, et al. Nature. 2015;520:633-639.