Neurexin directs partner-specific synaptic connectivity in C. elegans

Elife. 2018 Jul 24;7:e35692. doi: 10.7554/eLife.35692.


In neural circuits, individual neurons often make projections onto multiple postsynaptic partners. Here, we investigate molecular mechanisms by which these divergent connections are generated, using dyadic synapses in C. elegans as a model. We report that C. elegans nrx-1/neurexin directs divergent connectivity through differential actions at synapses with partnering neurons and muscles. We show that cholinergic outputs onto neurons are, unexpectedly, located at previously undefined spine-like protrusions from GABAergic dendrites. Both these spine-like features and cholinergic receptor clustering are strikingly disrupted in the absence of nrx-1. Excitatory transmission onto GABAergic neurons, but not neuromuscular transmission, is also disrupted. Our data indicate that NRX-1 located at presynaptic sites specifically directs postsynaptic development in GABAergic neurons. Our findings provide evidence that individual neurons can direct differential patterns of connectivity with their post-synaptic partners through partner-specific utilization of synaptic organizers, offering a novel view into molecular control of divergent connectivity.

Keywords: AChR; C. elegans; dendritic spine; neuroscience; neurotransmission; nicotinic acetylcholine receptor; synapse; synaptic divergence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / growth & development
  • Animals, Genetically Modified / metabolism*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • GABAergic Neurons / cytology
  • GABAergic Neurons / physiology*
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / physiology*
  • Receptors, Cholinergic
  • Receptors, Nicotinic / metabolism
  • Synapses
  • Synaptic Transmission*


  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules, Neuronal
  • Receptors, Cholinergic
  • Receptors, Nicotinic
  • nrx-1 protein, C elegans
  • Acetylcholine