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

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
Pages (from-to)864-9
Number of pages6
JournalScience
Volume287
Issue number5454
Publication statusPublished - 4 Feb 2000

Cite this

Verhage, M., Maia, A. S., Plomp, J. J., Brussaard, A. B., Heeroma, J. H., Vermeer, H., ... Südhof, T. C. (2000). Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science, 287(5454), 864-9.
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. / Synaptic assembly of the brain in the absence of neurotransmitter secretion. In: Science. 2000 ; Vol. 287, No. 5454. pp. 864-9.
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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.",
keywords = "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",
author = "M Verhage and Maia, {A S} and Plomp, {J J} and Brussaard, {A B} and Heeroma, {J H} and H Vermeer and Toonen, {R F} and Hammer, {R E} and {van den Berg}, {T K} and M Missler and Geuze, {H J} and S{\"u}dhof, {T C}",
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Verhage, M, Maia, AS, Plomp, JJ, Brussaard, AB, Heeroma, JH, Vermeer, H, Toonen, RF, Hammer, RE, van den Berg, TK, Missler, M, Geuze, HJ & Südhof, TC 2000, 'Synaptic assembly of the brain in the absence of neurotransmitter secretion' Science, vol. 287, no. 5454, pp. 864-9.

Synaptic assembly of the brain in the absence of neurotransmitter secretion. / 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.

In: Science, Vol. 287, No. 5454, 04.02.2000, p. 864-9.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Synaptic assembly of the brain in the absence of neurotransmitter secretion

AU - Verhage, M

AU - Maia, A S

AU - Plomp, J J

AU - Brussaard, A B

AU - Heeroma, J H

AU - Vermeer, H

AU - Toonen, R F

AU - Hammer, R E

AU - van den Berg, T K

AU - Missler, M

AU - Geuze, H J

AU - Südhof, T C

PY - 2000/2/4

Y1 - 2000/2/4

N2 - 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.

AB - 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.

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KW - Cell Differentiation

KW - Cell Division

KW - Gene Deletion

KW - Growth Cones/physiology

KW - Mice

KW - Mice, Knockout

KW - Munc18 Proteins

KW - Nerve Degeneration

KW - Nerve Tissue Proteins/genetics

KW - Neural Pathways

KW - Neuromuscular Junction/embryology

KW - Neurons/cytology

KW - Neurotransmitter Agents/metabolism

KW - Patch-Clamp Techniques

KW - Synapses/physiology

KW - Synaptic Transmission

KW - Synaptic Vesicles/metabolism

KW - Vesicular Transport Proteins

M3 - Article

VL - 287

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JO - Science

JF - Science

SN - 0036-8075

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ER -

Verhage M, Maia AS, Plomp JJ, Brussaard AB, Heeroma JH, Vermeer H et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science. 2000 Feb 4;287(5454):864-9.