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

First Author  Henderson NT Year  2019
Journal  Elife Volume  8
PubMed ID  30789343 Mgi Jnum  J:275936
Mgi Id  MGI:6304057 Doi  10.7554/eLife.41563
Citation  Henderson NT, et al. (2019) Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs. Elife 8:e41563
abstractText  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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