The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. 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. The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. 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. 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. Ribbon synapses are found in retinal photoreceptor cells, vestibular organ receptors, cochlear hair cells, retinal bipolar cells, and pinealocytes. The synaptic ribbon is a unique structure at the active zone of the synapse. It is positioned several nanometers away from the pre-synaptic membrane and tethers 100 or more synaptic vesicles. 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. The ribbon synapse was first identified in the retina as a thin, ribbon-like presynaptic projection surrounded by a halo of vesicles using transmission electron microscopy in the 1950s, as the technique was gaining mainstream usage. The photoreceptor ribbon synapse is around 30 nm in thickness. It sticks out into the cytoplasm around 200-1000 nm and anchors along its base to the arciform density which is an electron dense structure that is anchored to the presynaptic membrane. The arciform density is located within the synaptic ridge, a small evagination of the presynaptic membrane. Hair cells lack an arciform density so the anchor of this ribbon is considered to be invisible by electron microscope. 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 multiple filaments per vesicle. There are also voltage gated L-type calcium channels on the docking sites of the ribbon synapse which trigger neurotransmitter release. Specifically, ribbon synapses contain specialized organelles called synaptic ribbons, which are large presynaptic structures associated in the active zone. They are thought to fine-tune the synaptic vesicle cycle. Synaptic ribbons are in close proximity to synaptic vesicles, which, in turn, are close to the presynaptic neurotransmitter release site via the ribbon. Postsynaptic structures differ for cochlear cells and photoreceptor cells. Hair cells is capable of one action potential propagation for one vesicle release. One vesicle release from the presynaptic hair cell onto the postsynaptic bouton is enough to create an action potential in the auditory afferent cells. Photoreceptors allow one vesicle release for many action potential propagation. The rod terminal and cone ribbon synapse of the photoreceptors have horizontal synaptic spines expressing AMPA receptors with additional bipolar dendrites exhibiting the mGluR6 receptors. These structures allow for the binding of multiple molecules of glutamate, allowing for the propagation of many action potentials. The molecular composition between conventional neuronal synapse and ribbon synapse is surprisingly dissimilar. At the core of synaptic vesicle exocytosis machinery in vertebrate neuronal synapses is the SNARE complex. The minimally functional SNARE complex includes syntaxin 1, VAMP 1 and 2, and SNAP-25. 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. Additionally, no neuronal SNAREs were observed in hair cells using immunostaining, pointing to the possibility of a different exocytosis mechanism. However, several studies found SNARE mRNA and protein expressed in hair cell, perhaps indicating presence of a neuronal SNARE complex in ribbon synapse that is present in low levels and with very redundant components. Several proteins of the synaptic ribbon have also been found to be associated with conventional synapses. RIM (Rab3-interacting proteins) is a GTPase expressed on synaptic vesicles that is important in priming synaptic vesicles. Immunostaining has revealed the presence of KIF3A, a component of the kinesin II motor complex whose function is still unknown. The presynaptic cytomatrix proteins Bassoon and Piccolo are both expressed at photoreceptor ribbons, but Piccolo is only expressed at retinal bipolar synaptic ribbons. Bassoon is responsible for attaching itself to the base of the synaptic ribbons and subsequently anchoring the synaptic ribbons. The function of Piccolo is unknown. Also important is the filaments that tether the vesicles to the ribbon synapse. These are shed during high rates of exocytosis. The only unique protein associated with the synaptic ribbon is RIBEYE, first identified in purified synaptic ribbon from bovine retina. It is found to be a part of all vertebrate synaptic ribbons in ribbon synapses and is the central portion of ribbon synapses. RIBEYE interactions are required to form a scaffold formation protein of the synaptic ribbon. There has been a significant amount of research into the pre-synaptic cytomatrix protein Bassoon, which is a multi-domain scaffolding protein universally expressed at synapses in the central nervous system. Mutations in Bassoon have been shown to result in decreased synaptic transmission. However, the underlying mechanisms behind this observed phenomenon are not fully understood and are currently being investigated. It has been observed that in the retina of Bassoon-mutant mice, photoreceptor ribbon synapses are not anchored to pre-synaptic active zones during photoreceptor synaptogenesis. The photoreceptor ribbon synapses are observed to be free floating in the cytoplasm of the photoreceptor terminals. These observations have led to the conclusion that Bassoon plays a critical role in the formation of the photoreceptor ribbon synapse. In correspondence to its activity, ribbon synapses can have synaptic ribbons that vary in size. In mouse photoreceptor synapses when the neurotransmitter release rate is high and exocytosis is high, the synaptic ribbons are long. When neurotransmitter release rate is low and exocytosis is low, the synaptic ribbons are short. A current hypothesis is that synaptic ribbons can enlarge by the addition of more RIBEYE subunit.