Quantal analysis estimates docking site occupancy determining short-term depression at hippocampal glutamatergic...

Area of Science:

• Neuroscience
• Synaptic Physiology
• Cellular Neuroscience

Background:

• Synaptic vesicles (SVs) dock at release sites before fusion, with occupancy probability influencing synaptic strength.
• Direct estimation of SV site occupancy is challenging due to its interdependence with other synaptic parameters.
• The precise role of site occupancy in synaptic depression remains largely undetermined.

Purpose of the Study:

• To directly estimate the occupancy probability of release/docking sites by SVs at hippocampal mossy fibre-CA3 interneuron synapses.
• To elucidate the contribution of site occupancy to short-term synaptic depression.
• To investigate the influence of external calcium concentration on occupancy, release probability, and synaptic depression.

Main Methods:

• Direct estimation of occupancy probability using statistical analysis of vesicular events detected by deconvolution.
• Analysis of quantal amplitudes and SV counts during repetitive stimulation.
• Model simulations to assess the impact of occupancy, release probability, and replenishment on synaptic depression.

Main Results:

• The hippocampal mossy fibre-CA3 interneuron synapse exhibits high initial occupancy (∼0.85) and release probability (∼0.8) under high calcium conditions.
• Quantal size and release/docking site number showed minimal influence on synaptic depression extent.
• Model simulations confirmed that initial occupancy, high release probability, and slow replenishment determine synaptic depression kinetics.

Conclusions:

• Synaptic vesicle site occupancy is a critical determinant of short-term synaptic depression at hippocampal glutamatergic synapses.
• Changes in external calcium concentration modulate both occupancy and release probability, thereby shaping synaptic depression.
• The findings highlight site occupancy as a key factor in regulating synaptic transmission dynamics.