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Publication

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

eLife | 2019

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.

Pubmed ID: 30789343 RIS Download

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Associated grants

Agency: NIDA NIH HHS, United States
Id: R01 DA022727
Agency: NINDS NIH HHS, United States
Id: RO1NS050835
Agency: NINDS NIH HHS, United States
Id: R01NS106906
Agency: NINDS NIH HHS, United States
Id: R01 NS050835
Agency: NIDA NIH HHS, United States
Id: R01DA022727

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