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Cited by 15Neuroscience and Neuropharmacology ResearchAxon Guidance and Neuronal SignalingGenetics and Neurodevelopmental Disorders

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

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Henderson, Nathan T, Le Marchand, Sylvain J, Hruska, Martin, Hippenmeyer, Simon, Luo, Liqun, Dalva, Matthew B·2019·eLife
DOI 10.7554/elife.41563PMC PMC6384025
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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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  • Ephrin stimulates excitatory synapses development and is closely related to neurogenesis, plasticity and learning.

    “Also, it has been shown that ephrin stimulates excitatory synapses development [127–129] and is closely related to neurogenesis, plasticity and learning [93].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [128]

    The source is cited for the first clause, not the neurogenesis, plasticity, and learning clause, which has a separate citation. Its Introduction and Discussion support a role for ephrin-B3 in regulating excitatory synapse density during development, but the Introduction explicitly says it is not required for synapse formation; it controls the local distribution of synapses instead. Thus, saying broadly that ephrin stimulates synapse development overstates the finding. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Henderson, N. T., Le Marchand, S. J., Hruska, M., Hippenmeyer, S., Luo, L., & Dalva, M. B.
Affiliations
  • Thomas Jefferson University (US)
  • Bio-Imaging Center, University of Delaware, Newark, United States
  • Institute of Science and Technology Austria (AT)
  • Howard Hughes Medical Institute (US)
Corresponding author
Dalva, Matthew B
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2019-02-21
Volume
8
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.41563
PMC
PMC6384025
OpenAlex
W2917093014
Cited by
15
References
4
Citations by year
2025: 5 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 1
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Medicine Forum (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Neurological Disorders and Stroke (RO1NS050835, R01NS106906)
  • National Institute on Drug Abuse (R01DA022727)
  • Farber Family Fund
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
ephrin-B3, EphB receptors, synaptic density, excitatory synapses, cortical connectivity, dendritic spine density
MeSH terms
Animals, Cell Communication, Cerebral Cortex, Nerve Net, Neurons, Ephrin-B3, Mice

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