Passive Diffusion as a Mechanism Underlying Ribbon Synapse Vesicle Release and Resupply

摘要: Synaptic ribbons are presynaptic protein structures found at many synapses that convey graded, “analog” sensory signals in the visual, auditory, and vestibular pathways. Ribbons, typically anchored to membrane surrounded by tethered synaptic vesicles, thought regulate or facilitate vesicle delivery membrane. No direct evidence exists, however, indicate how vesicles interact with ribbon or, once attached, move along ribbon's surface reach release sites its base. To address these questions, we have created, validated, tested a passive diffusion model of retinal rod bipolar cell synapses. We used axial (bright-field) electron tomography scanning transmission microscopy obtain 3D rat terminals 1-μm-thick sections tissue an isotropic spatial resolution ∼3 nm. The resulting were then incorporated previously published estimates dynamics into numerical simulations accurately reproduced electrophysiologically measured release/replenishment rates pool sizes. suggest that, under physiologically realistic conditions, crowded on gives rise flow field enhances without requiring active transport mechanism. Numerical ribbon–vesicle interactions predict transient binding unbinding multiple tethers each may achieve sufficiently tight association while permitting fast is required sustain high rates.