Munc18-1 Expression Levels Control Synapse Recovery by Regulating Readily Releasable Pool Size

Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression of the presynaptic gene munc18-1 suffer from increased depression during intense stimulation at glutamatergic, GABAergic, and neuromuscular synapses. Converse...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (48), p.18332-18337
Main Authors: Toonen, Ruud F. G., Wierda, Keimpe, Sons, Michèle S., de Wit, Heidi, Cornelisse, L. Niels, Brussaard, Arjen, Plomp, Jaap J., Verhage, Matthijs
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Electrophysiology
Gene expression
Gene Expression Regulation
Genes
Genetic variation
Genomics
Heterozygote
Kinetics
Mice
Mice, Transgenic
Microscopy, Electron
Munc18 Proteins - genetics
Munc18 Proteins - metabolism
Neurons
Neuroscience
Neurosciences
Neurotransmitters
Receptors
SNARE proteins
Synapses
Synaptic Transmission
Synaptic Vesicles - genetics
Synaptic Vesicles - metabolism
Synaptic Vesicles - ultrastructure
Time Factors
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Summary:Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression of the presynaptic gene munc18-1 suffer from increased depression during intense stimulation at glutamatergic, GABAergic, and neuromuscular synapses. Conversely, munc18-1 overexpression makes these synapses recover faster. Concomitant changes in the readily releasable vesicle pool and its refill kinetics were found. The number of vesicles docked at the active zone and the total number of vesicles per terminal correlated with both munc18-1 expression levels and the size of the releasable vesicle pool. These data show that varying expression of a single gene controls synaptic recovery by modulating the number of docked, release-ready vesicles and thereby replenishment of the secretion capacity.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0608507103