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Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2012 Feb 21; Vol. 109 (8), pp. E515-23. Date of Electronic Publication: 2012 Jan 30. - Publication Year :
- 2012
-
Abstract
- Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.
- Subjects :
- Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Cerebral Cortex pathology
Mice
Mice, Knockout
Neurons metabolism
Synaptic Vesicles enzymology
Synaptic Vesicles ultrastructure
Up-Regulation
Dynamins metabolism
Mutation genetics
Synaptic Transmission physiology
Synaptic Vesicles metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 109
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 22308498
- Full Text :
- https://doi.org/10.1073/pnas.1121626109