Abstract No.: | C-B3059 |
Country: | Canada |
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Title: | THE IMPORTANCE OF MECHANISMS DOWNSTREAM OF SYNAPTIC VESICLE PRIMING IN THE REGULATION OF NEUROTRANSMITTER RELEASE PROBABILITY. |
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Authors/Affiliations: | 1 Terry McCarville; 1 Jacob Matz; 1 Julia Frenette; 1 Stefan Krueger*;
1 Dalhousie University, Halifax, NS, Canada; 1Dept. of Physiology and Biophysics, 2Neuroscience Institute, and 3Undergraduate Neuroscience Program, Halifax, NS, Canada
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Content: | Objectives. Neurotransmitter release is a multi-step process during which synaptic vesicles dock to the active zone cytomatrix, are primed for release by formation of a complex between SNARE proteins on synaptic vesicle and plasma membrane, and finally fuse with the plasma membrane in a step that crucially depends on influx of calcium through nearby voltage-gated calcium channels (VGCCs). In principle, the likelihood with which an action potential elicits neurotransmitter release at a given synapse (release probability or pr) can be regulated at each of these steps. We reexamining the previously reported finding that the size of the readily releasable pool of docked and primed synaptic vesicles at cortical synapses correlates closely with pr, suggesting that the probability of neurotransmitter release is largely determined through the regulation of synaptic vesicle docking and/or priming.
Materials and Methods. We are using a genetically encoded sensor of synaptic vesicle exocytosis, synaptophysin-pHluorin, to quantify pr and the readily releasable pool of synaptic vesicles at individual synapses between dissociated hippocampal neurons in culture.
Results. We have observed that adjacent release sides made by a single axon can have similar pools of readily releasable vesicles, yet differ widely in their release probability. We are currently investigating whether differences in pr between synapses with similar readily releasable synaptic vesicle pools can be attributed to disparities in the spatial coupling of primed synaptic vesicles and VGCCs.
Conclusion. Our results suggest that mechanisms downstream of vesicle priming, possibly variations in the spatial coupling between VGCCs and primed synaptic vesicles, have a decisive influence on pr.
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