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Examination of Synaptic Vesicle Recycling Using FM Dyes During Evoked, Spontaneous, and Miniature Synaptic Activities
Published on: March 31, 2014
Vesicular release mode shapes the postsynaptic response at hippocampal synapses.
1Department of Neurology, University of Cincinnati, Vontz Center for Molecular Studies, 3125 Eden Avenue, Cincinnati, OH 45267, USA. david.richards@cchmc.org
The Journal of Physiology
|September 16, 2009
Summary
Synaptic vesicle exocytosis occurs via distinct pathways, influencing neurotransmitter release and receptor activation. Kiss-and-run exocytosis leads to minimal AMPA receptor activation, unlike full fusion, impacting synaptic transmission throughput.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Physiology
Background:
- Synaptic transmission relies on neurotransmitter release from vesicles.
- Multiple exocytosis routes exist, but their regulation and implications are not fully understood.
- Two distinct synaptic vesicle exocytosis modes are observable at hippocampal synapses using FM1-43.
Purpose of the Study:
- To investigate the distinct postsynaptic consequences of two identified synaptic vesicle exocytosis modes.
- To elucidate the role of fusion pore dynamics in synaptic transmission.
- To understand how different exocytosis pathways affect AMPA and NMDA receptor activation.
Main Methods:
- Electrophysiological recording
- Fluorescence imaging with FM1-43
- Pharmacological manipulation (cyclothiazide) to block AMPA receptor desensitization.
Main Results:
- Kiss-and-run exocytosis results in negligible AMPA receptor activation, while full fusion elicits robust responses.
- NMDA receptors are strongly activated by glutamate delivered via kiss-and-run exocytosis.
- Slow glutamate release during kiss-and-run leads to AMPA receptor desensitization, not just insufficient activation.
Conclusions:
- Findings support the existence of a fusion pore-mediated exocytosis mode.
- Distinct exocytic modes have direct and differential impacts on postsynaptic receptor activation.
- These exocytic pathways significantly modulate the overall throughput of synaptic transmission.
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