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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

1
Department of Neuroscience, The Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States.
2
Department of Neuroscience, University of Pennsylvania, Philadelphia, United States.
3
Bio-Imaging Center, University of Delaware, Newark, United States.
4
Institute of Science and Technology Austria, Klosterneuburg, Austria.
5
Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
#
Contributed equally

Abstract

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

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