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Brittin et al. 2021

A multi-scale brain map derived from whole-brain volumetric reconstructions

Brittin, C.A., Cook, S.J., Hall, D.H. et al
Nature 591, 105–110
Published: 24 February 2021

Abstract

  • Nerve ring is derived from integrating the volumetric reconstructions from two animals with corresponding synaptic and gap junctional connectomes (Cook et al 2019)
  • C.elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and identify a canditate reference connectome for the core circuit.
  • Using this reference, they propose a modular network architecture of C.elegans brain that supports sensory computation and integration, sensorimotor convergence and brain-wide coordination.
  • These findings reveal scalable and robust features of brain organisation that may be universal across phyla.

Main

  • invariant cell lineage and anatomy of C.elegans might suggest that its connectome is too invariant
  • small sample size of available reconstructions has precluded a reliable estimate of the reproducibility and variability of the synaptic connectome
  • the synaptic wiring has been exhaustively characterised (ref to be inserted) but the spatial proximity of neurons is only partially described (ref to be inserted).

Data

  • https://zenodo.org/records/4383277
  • https://zenodo.org/records/4383277
  • two complete volumetric reconstructions of the C.elegans nerve ring from previously published EMs (ref.) -adult -larval stage 4 (L4) worm
  • two series of EMs span approx the same vol. with a length of 36 micrometres, starting in the anterior and ending in the ventral ganglia
  • the reconstructiosn of these two nerve rings provide the first complete, nanoscale-resolution datasets of all neuronal membrane contacts of any neuropil.
  • "contactome": the set of membrane contacts of the brain
  • they define two neurons as immediate neighbours if the membranes along their neural processes are physically adjacent in at least one EM.
  • to characterise synaptic pathways within a spatial contex, they integrated volumetric reconstructions with recent rescoring of synapses on the same L4 and adult worms (Cook et al) -for validation and comparison with other datasets (White et al, Witvliet et al)

Discussion

  • Despite the C.elegans connectome being available for over 30 years, the delineation of functions within its main neuropil is still incomplete
  • There are no physical boundaries within the nerve ring, but their analysis points to the spatial clustering of neural processes into 5 neighbourhoods.
  • the concept of a reference connectome was key to their brain map and the modelling framework they sued to establish thsi reference can be accomodated for future connectomes.
  • Connectome consists of a core, conserved circuit that is embedded in a considerably variable background
  • Due to technical limitations of synaptic scoring, it is hard to determine the extent of the variability
  • requires multiple further connectomes
  • conserved synapes- like most variable ones- are constrained by the "contactome"
  • If the baseline functionality of the animal is represented by a core circuit, the variable component could support redundancy, individuality and plasticity