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Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs
Nathan T Henderson1,2, Sylvain J Le Marchand3, Martin Hruska1
1Department of Neuroscience, The Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, United States.
Elife
|February 22, 2019
Summary
Ephrin-B3 (eB3) mediates cell-cell competition to regulate synapse density in cortical networks. This trans-synaptic signaling determines which neurons receive more synapses, independent of neuronal activity.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Cortical networks exhibit sparse connectivity, yet high local connection probabilities.
- Cell-intrinsic factors, not just proximity, are suggested to govern neuronal connectivity.
Purpose of the Study:
- To identify molecular mechanisms regulating synapse density in cortical neurons.
- To investigate the role of ephrin-B3 in cell-cell competition for synaptic connections.
Main Methods:
- Utilized a microisland culture system to isolate cell-cell competition dynamics.
- Employed Mosaic Analysis with Double Markers (MADM) in vivo and in vitro in mouse models.
- Assessed synapse density and spine density in relation to ephrin-B3 levels.
Main Results:
- Identified ephrin-B3 (eB3) as a key mediator of synapse density.
- Demonstrated that eB3 drives a cell-cell competition for synaptic inputs.
- Showed that relative eB3 levels control spine density in L5/6 cortical neurons.
- Confirmed eB3's role in synapse density regulation is independent of neuronal activity.
Conclusions:
- Ephrin-B3 signaling mediates a competitive mechanism for synapse formation.
- Trans-synaptic organizing proteins like eB3 control synapse number based on cell-cell interactions.
- This competitive mechanism provides a novel understanding of synaptic connectivity regulation.
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