Synapse-to-synapse variation in mean synaptic vesicle size and its relationship with synaptic morphology and function

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Physiology

Background:

• Synaptic vesicle (SV) size is a key determinant of neurotransmitter release.
• Variability in mean SV size across excitatory hippocampal synapses suggests potential regulation of transmitter release.
• Understanding factors influencing SV size is fundamental to synaptic function.

Purpose of the Study:

• Investigate parameters influencing mean synaptic vesicle size.
• Determine the relationship between mean SV size and synaptic morphology.
• Examine the effect of osmotic pressure and neuronal activity on SV size.

Main Methods:

• Analysis of synapse-to-synapse variability in SV size across species and brain regions.
• Three-dimensional reconstructions of synapses from serial ultrathin sections.
• Experimental manipulation of osmotic pressure and chronic neuronal activity levels.

Main Results:

• Synapse-to-synapse variability in SV size is a widespread phenomenon.
• Mean SV size did not correlate with postsynaptic density area, synaptic cleft volume, bouton volume, or total SV number.
• Reduced osmotic pressure significantly decreased SV size, while increased osmotic pressure had no effect.
• SV size remained constant during long-lasting, high-frequency stimulation and did not adapt to chronic activity changes.

Conclusions:

• Synaptic vesicle size is influenced by osmotic pressure, with lower pressure leading to smaller vesicles.
• Synaptic morphology and chronic activity levels are not primary regulators of mean SV size.
• The synaptic vesicle cycle maintains consistent SV size even under prolonged high-frequency stimulation.