Synaptic assembly of the brain in the absence of neurotransmitter secretion

M Verhage, A S Maia, J J Plomp, A B Brussaard, J H Heeroma, H Vermeer, R F Toonen, R E Hammer, T K van den Berg, M Missler, H J Geuze, T C Südhof

Research output: Contribution to journalArticleAcademicpeer-review

1040 Citations (Scopus)


Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections.

Original languageEnglish
Pages (from-to)864-9
Number of pages6
Issue number5454
Publication statusPublished - 4 Feb 2000


  • Animals
  • Apoptosis
  • Brain/cytology
  • Cell Differentiation
  • Cell Division
  • Gene Deletion
  • Growth Cones/physiology
  • Mice
  • Mice, Knockout
  • Munc18 Proteins
  • Nerve Degeneration
  • Nerve Tissue Proteins/genetics
  • Neural Pathways
  • Neuromuscular Junction/embryology
  • Neurons/cytology
  • Neurotransmitter Agents/metabolism
  • Patch-Clamp Techniques
  • Synapses/physiology
  • Synaptic Transmission
  • Synaptic Vesicles/metabolism
  • Vesicular Transport Proteins

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