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

ELife
Nathan T HendersonMatthew B Dalva

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.

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Citations

Jun 24, 2021·Cell Reports·Ximena ContrerasSimon Hippenmeyer
Jan 1, 2021·Current Opinion in Neurobiology·Rüdiger Klein, Ronald Jeroen Pasterkamp

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Methods Mentioned

BETA
transfection
transgenic
FACS
transfections

Software Mentioned

pFUGW
Gateway
Leica application suite
RNAscope
ImageJ

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