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. |