title: Synaptic assembly of the brain in the absence of neurotransmitter secretion.
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.
authors.affiliation: Molecular Neuroscience, Rudolf Magnus Institute, University of Utrecht Medical Centre, Utrecht, Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Verhage
authors.forename: A S
authors.initials: AS
authors.lastname: Maia
authors.forename: J J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: A B
authors.initials: AB
authors.lastname: Brussaard
authors.forename: J H
authors.initials: JH
authors.lastname: Heeroma
authors.forename: H
authors.initials: H
authors.lastname: Vermeer
authors.forename: R F
authors.initials: RF
authors.lastname: Toonen
authors.forename: R E
authors.initials: RE
authors.lastname: Hammer
authors.forename: T K
authors.initials: TK
authors.lastname: van den Berg
authors.forename: M
authors.initials: M
authors.lastname: Missler
authors.forename: H J
authors.initials: HJ
authors.lastname: Geuze
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D017353:Gene Deletion; D020439:Growth Cones / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D051938:Munc18 Proteins; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways; D009469:Neuromuscular Junction / Q000196:embryology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D033921:Vesicular Transport Proteins
chemical_list: D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C497938:Stxbp1 protein, mouse; D033921:Vesicular Transport Proteins