Send to

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

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

Author information

Department of Neuroscience, The Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States.
Department of Neuroscience, University of Pennsylvania, Philadelphia, United States.
Bio-Imaging Center, University of Delaware, Newark, United States.
Institute of Science and Technology Austria, Klosterneuburg, Austria.
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Contributed equally


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.


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

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center