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Witvliet et al. 2021

Connectomes across development reveal principles of brain maturation

Witvliet, D., Mulcahy, B., Mitchell, J.K. et al
Nature 596, 257–261
Published: 4 August 2021

Datasets

See also www.nemanode.org

Data

  • eight isogenic C.elegans from L1 to adult -three L1, two L2, and one L3 worm to capture continuous connectomic changes
  • reconstructed two adults to make direct comparisons between animals of the same age and the original published connectome (White et al 1984)

Brain reconstruction

  • Brain was defined as the nerve ring, ventral ganglion and neuropil anterior of the ventral sub-lateral commissures.
  • every neuron, glia and muscle was annotated for chemical synapses to generate a connectome of the brain.
  • Gap junctions were partially annotated and excluded from analyses.
  • Chemical synapse weight was assessed by both the number and size of synapses.

Connection classification

  • 3,113 connections (averaging 1,292 per dataset) were assigned as stable, variable or developmentally dynamic
  • 1,647 connections (averaging 323 per dataset) had no more than two synapses in two or more datasets and were left-right asymmetric. (classed as variable)
  • 1,466 connections were pooled by left-right pairs, resulting in 658 pair connections

Comparison with original dataset

  • As observed in the original dataset, some variability in cell body position and neurite trajectory was observed
  • every cell was unambiguously identified in every dataset becaused combined anatomical features and neighbourhood for each cell is unique.
  • because individual muscles were not traced in the original, they complete this dataset by tracing through all head muscles using the EM hosted by www.wormatlas.org
  • individual muscle arms were identified by their characteristic location within the brain, which were confirmed by tracing their arms back to their cell body in several datasets.

Minimally corrected dataset (N2U, Cook et al., 2019)

  • WormAtlas hosts a wiring of N2U connectome from (Cook et al. 2019)
  • They noted errors in muscle identification and synapse annotation in this reannotation
  • corrected identity of muscle pairs (VL1-VL2, VR1-VR2, DL2-DL3, DR2-DR3, DL5-DL6, DR5-DR6, VL5-VL6, VR5-VR6)
  • muscles were not traced at all in the brain, and only one of more than 50 synapses onto muscle VR2 was annotated

Limitations

  • Not included gap junctions
  • improvement in sample prepation and analysis are needed to reach the same level of confidence and throughput as they reached for chemical synaptic networks throughout development
  • analysed only one connectome at most timepoints
  • could not assess animal-to-animal variability at each age