Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs

Elife. 2019 Feb 21;8:e41563. doi: 10.7554/eLife.41563.


Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control spine density in layer 5 and 6 neurons. MADM cortical neurons in vitro reveal that eB3 controls synapse density independently of action potential-driven activity. Our findings illustrate a new class of competitive mechanism mediated by trans-synaptic organizing proteins which control the number of synapses neurons receive relative to neighboring neurons.

Keywords: Mouse; Rat; activity-independent; connectivity; mouse; neuroscience; synaptogenesis; trans-synaptic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication*
  • Cerebral Cortex / cytology*
  • Ephrin-B3 / metabolism*
  • Mice
  • Nerve Net / physiology*
  • Neurons / metabolism*


  • Ephrin-B3