Synaptic structural complexity as a factor enhancing probability of calcium-mediated transmitter release

Area of Science:

• Neuroscience
• Computational Biology
• Cellular Biology

Background:

• Synaptic terminals exhibit structural complexity with varying numbers and spacing of active zones.
• Understanding how active zone proximity influences calcium dynamics and neurotransmission is crucial for synaptic function.

Purpose of the Study:

• To test the hypothesis that closely spaced active zones enhance localized calcium ion concentration and neurotransmission probability.
• To evaluate the impact of separation distance between active zones on intracellular calcium concentration.

Main Methods:

• A reaction-diffusion model for calcium (Ca2+) entry into presynaptic terminals was employed.
• The model incorporated intracellular buffers and voltage-activated Ca2+ channels, informed by freeze-fracture micrographs.

Main Results:

• Localized calcium clouds from discrete active zones can overlap, enhancing spatial calcium concentration, especially when separated by ≤200 nm.
• Enhanced intracellular calcium concentration ([Ca2+]i) at active zones and between them was observed compared to single active zones.
• Immobile buffers led to residual calcium accumulation, which was faster at closely spaced active zones during stimulation trains.

Conclusions:

• Synapses with closely associated active zones likely exhibit enhanced release probability, potentially recruiting them at low neuronal activity frequencies.
• Synaptic complexity provides a mechanism for frequency facilitation, increasing neurotransmitter release with higher neuronal activity.
• Variations in synaptic complexity offer a mechanism for short-term plasticity in transmitter release.