Faculty Collaboration Database

Tissue-specific dynamin-1 deletion at the calyx of Held decreases short-term depression through a mechanism distinct from vesicle resupply. Proc Natl Acad Sci U S A 2016 May 31;113(22):E3150-8

Date

05/18/2016

Pubmed ID

27185948

Pubmed Central ID

PMC4896691

DOI

10.1073/pnas.1520937113

Scopus ID

2-s2.0-84971572911 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Dynamin is a large GTPase with a crucial role in synaptic vesicle regeneration. Acute dynamin inhibition impairs neurotransmitter release, in agreement with the protein's established role in vesicle resupply. Here, using tissue-specific dynamin-1 knockout [conditional knockout (cKO)] mice at a fast central synapse that releases neurotransmitter at high rates, we report that dynamin-1 deletion unexpectedly leads to enhanced steady-state neurotransmission and consequently less synaptic depression during brief periods of high-frequency stimulation. These changes are also accompanied by increased transmission failures. Interestingly, synaptic vesicle resupply and several other synaptic properties remain intact, including basal neurotransmission, presynaptic Ca(2+) influx, initial release probability, and postsynaptic receptor saturation and desensitization. However, acute application of Latrunculin B, a reagent known to induce actin depolymerization and impair bulk and ultrafast endocytosis, has a stronger effect on steady-state depression in cKO than in control and brings the depression down to a control level. The slow phase of presynaptic capacitance decay following strong stimulation is impaired in cKO; the rapid capacitance changes immediately after strong depolarization are also different between control and cKO and sensitive to Latrunculin B. These data raise the possibility that, in addition to its established function in regenerating synaptic vesicles, the endocytosis protein dynamin-1 may have an impact on short-term synaptic depression. This role comes into play primarily during brief high-frequency stimulation.

Author List

Mahapatra S, Fan F, Lou X

Author

Xuelin Lou PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Depression
Dynamin I
Endocytosis
Excitatory Postsynaptic Potentials
Female
Fluorescent Antibody Technique
Male
Mice
Mice, Knockout
Neurons
Organ Specificity
Patch-Clamp Techniques
Synapses
Synaptic Transmission
Synaptic Vesicles