This, in turn, causes the synaptic vesicles to move toward the plasma membrane nearest the synapse. As though magically, just the right number of vesicles dock and fuse to the plasma membrane, and just the right amount of neurotransmitter is released into the gap where it diffuses. It then binds to specific receptors on the postsynaptic neuron and triggers sufficient electrical stimulation to perpetuate the message. Technological advances have provided scientists with the means to measure changes in electrical potential between poles of neurons, gauge calcium concentrations both inside and outside of the cell, and design models of neurotransmitter release. However, technical limitations have relegated much of the synaptic junction to black box status.
Numerous questions remain unanswered and even more remain unasked.
Recently, technologies have been adapted for the neurosciences that shed light on the mechanisms of neurotransmission and provide some answers to the remaining questions. Their images depict the intricate molecular ballet performed by synaptic vesicles as they move toward the membrane, dock, and fuse. Because this technique allows for the direct observation of the movements of fluorescently labeled proteins, researchers can measure how soon before fusion the proteins are recruited to docking sites and how soon they are dismissed. Because synaptic terminals of neurons will stick to glass, the researchers used total internal reflection microscopy, an optical technique that precisely and instantaneously measures the distance between a flat surface and a microscopic sphere. Because of the difference in refractive indices between the sphere and the glass and the resulting nonuniform illumination by the evanescent wave passing through the sphere, the sphere scatters light in direct proportion to its distance from the flat surface.