Synaptic assembly of the brain in the absence of neurotransmitter secretion

Matthijs Verhage, Ascanio S. Maia, Jaap J. Plomp, Arjen B. Brussaard, Joost H. Heeroma, Hendrika Vermeer, Ruud F. Toonen, Robert E Hammer, Timo K. Van Den Berg, Markus Missler, Hans J. Geuze, Thomas C. Südhof

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894 Scopus citations

Abstract

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 (US)
Pages (from-to)864-869
Number of pages6
JournalScience
Volume287
Issue number5454
DOIs
StatePublished - Feb 4 2000

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    Verhage, M., Maia, A. S., Plomp, J. J., Brussaard, A. B., Heeroma, J. H., Vermeer, H., Toonen, R. F., Hammer, R. E., Van Den Berg, T. K., Missler, M., Geuze, H. J., & Südhof, T. C. (2000). Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science, 287(5454), 864-869. https://doi.org/10.1126/science.287.5454.864