VEGF modulates synaptic activity in the developing spinal cord

Dev Neurobiol. 2014 Nov;74(11):1110-22. doi: 10.1002/dneu.22187. Epub 2014 May 24.


Although it has been documented that the nervous and the vascular systems share numerous analogies and are closely intermingled during development and pathological processes, interactions between the two systems are still poorly described. In this study, we investigated whether vascular endothelial growth factor (VEGF), which is a key regulator of vascular development, also modulates neuronal developmental processes. We report that VEGF enhances the gamma-aminobutyric acid (GABA)/glycinergic but not glutamatergic synaptic activity in embryonic spinal motoneurons (MNs), without affecting MNs excitability. In response to VEGF, the frequency of these synaptic events but not their amplitude was increased. Blocking endogenous VEGF led to an opposite effect by decreasing frequency of synaptic events. We found that this effect occurred specifically at early developmental stages (E13.5 and E15.5) and vanished at the prenatal stage E17.5. Furthermore, VEGF was able to increase vesicular inhibitory amino acid transporter density at the MN membrane. Inhibition of single VEGF receptors did not modify electrophysiological parameters indicating receptor combinations or an alternative pathway. Altogether, our findings identify VEGF as a modulator of the neuronal activity during synapse formation and highlight a new ontogenic role for this angiogenic factor in the nervous system.

Keywords: angiogenic factors; development; neuronal activity; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Age Factors
  • Animals
  • Animals, Newborn
  • Blood Vessels / metabolism
  • Embryo, Mammalian
  • Glycine / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Motor Neurons / drug effects*
  • Neurotransmitter Agents / pharmacology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Spinal Cord / cytology*
  • Spinal Cord / embryology*
  • Synaptic Potentials / drug effects*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology*
  • gamma-Aminobutyric Acid / metabolism


  • Homeodomain Proteins
  • Neurotransmitter Agents
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • enhanced green fluorescent protein
  • vascular endothelial growth factor A, mouse
  • Hb9 protein, mouse
  • Green Fluorescent Proteins
  • gamma-Aminobutyric Acid
  • Glycine