[4][5][6] This interpretation has recently been questioned at the inner hair cell ribbon synapse, where it has been instead proposed that exocytosis is described by uniquantal (i.e., univesicular) release shaped by a flickering vesicle fusion pore.
[7] These unique features specialize the ribbon synapse to enable extremely fast, precise and sustained neurotransmission, which is critical for the perception of complex senses such as vision and hearing.
[8] Each pre-synaptic cell can have from 10 to 100 ribbons tethered at the membrane, or a total number of 1000–10000 vesicles in close proximity to active zones.
[9] The ribbon synapse was first identified in the retina as a thin, ribbon-like presynaptic projection surrounded by a halo of vesicles[10] using transmission electron microscopy in the 1950s, as the technique was gaining mainstream usage.
[11] The ribbon's surface has small particles that are around 5 nm wide where the synaptic vesicles tether densely via fine protein filaments.
There are also voltage gated L-type calcium channels on the docking sites of the ribbon synapse which trigger neurotransmitter release.
[14] In contrast, genetic ablation or application of botulinum, targeting SNAP-25, syntaxin 1–3, and VAMP 1–3, did not affect inner hair cell ribbon synapse exocytosis in mice.
[15] Additionally, no neuronal SNAREs were observed in hair cells using immunostaining,[15] pointing to the possibility of a different exocytosis mechanism.
Ribbon synapses enable neurons to transmit light signals over a dynamic range of several orders of magnitude in intensity.
[24] To accomplish this level of performance, the sensory neurons of the eye maintain large pools of fast releasable vesicles that are equipped with ribbon synapses.
This enables the cell to exocytose hundreds of vesicles per second, greatly exceeding the rate of neurons without the specialized ribbon synapse.
[24] During exocytosis at the bipolar ribbon synapse, vesicles are seen to pause at the membrane and then upon opening of the calcium channels to promptly release their contents within milliseconds[citation needed].
[30] However it has been recently proposed that uniquantal release with fusion pore flickering is the most plausible interpretation of the found current distribution.
It has been shown that the skewness of the current amplitude distribution is well explained by different time courses of neurotransmitter release of a single vesicles with a flickering fusion pore.
The bipolar cell active zone of the ribbon synapse can release neurotransmitter continuously for hundreds of milliseconds during strong stimulation.
Once the presynaptic vesicles have been depleted, the bipolar cell's releasable pool requires several seconds to refill with the help of ATP hydrolysis.
[11] Research has shown that abnormal expression of otoferlin, a ribbon synapse associated protein, impairs exocytosis of ribbon-bound vesicles in auditory inner hair cells.
The protein otoferlin is observed phenotypically in human auditory inner hair cells, and abnormal expression has been linked with deafness.
In humans, cochlear implants have shown to reduce the debilitating effects of abnormal otoferlin expression by surpassing the synapse associated with the auditory inner hair cells.
[citation needed] The genetic code for retinal subunits associated with impaired scotopic vision and rod photoreceptor degradation are conserved at approximately 93% between mice and humans.
[31] Further research into the abnormal functioning of these mechanisms could open the door to therapeutic techniques to relieve auditory and visual impairments.