Key Points
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Ribbon synapses subserve transmitter release from 'tonic' sensory cells, including retinal photoreceptors and bipolar cells, and hair cells of vestibular, auditory and lateral line organs.
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Synaptic 'ribbons' are electron-dense bodies attached to the plasma membrane at points of contact with postsynaptic neurons. Numerous small vesicles, likely to contain the neurotransmitter glutamate, are tethered to the ribbon. Ribbon structure, and presumably function, varies considerably among — and even within — different cell types.
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Postsynaptic architecture of retinal photoreceptor ribbon synapses is complex, with glutamate released from a single ribbon reaching multiple functionally distinct targets. This divergence allows each point in visual space to be sampled in parallel by separate neural pathways concerned with different aspects of vision.
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Vesicular fusion at ribbon synapses is driven by calcium influx through L-type, dihydropyridine-sensitive voltage-gated calcium channels. These have rapid activation and deactivation kinetics, and relatively little inactivation — consistent with the requirement to support ongoing, tonic release, and to vary rapidly with stimulus-evoked changes in membrane potential.
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'Tonic' vesicular release at ribbons differs qualitatively and quantitatively from 'phasic' release driven by action potentials at conventional neuronal synapses. Accordingly, ribbon synapses may employ a number of unique vesicle- and ribbon-associated proteins that differ from those of the canonical SNARE complex.
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In addition to supporting impressive rates of ongoing vesicular release, ribbons seem also to employ a mechanism of 'multivesicular release' — simultaneous fusion of several synaptic vesicles that can occur without a coordinating change in membrane potential through as yet unknown means.
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Ribbon synapses in hair cells of the mammalian cochlea meet special challenges; each one is the sole presynaptic source for an individual 'type I' cochlear afferent neuron, some of which have spontaneous activity of 100 action potentials per second, and stimulus-driven rates several times higher.
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Remarkably, each cochlear inner hair cell is presynaptic to 10–30 afferent neurons, among which spontaneous rate, acoustic threshold and response dynamics differ. The emerging view is that individual ribbons of one hair cell can vary at least in the size of the ribbon and the number of associated voltage-gated calcium channels, although additional variations in synaptic release proteins and/or calcium metabolism could further contribute to functional variation.
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Ribbon synapses seem to be capable of multiple modes of transmission, which could coexist to different degrees depending on the demands of a particular sensory system. Therefore, it seems that ribbon synapses are at least as diverse as conventional synapses. It remains to be determined how the presynaptic and postsynaptic architectures of the various ribbon-type synapses are adjusted to achieve this functional diversity.
Abstract
Sensory synapses of the visual and auditory systems must faithfully encode a wide dynamic range of graded signals, and must be capable of sustained transmitter release over long periods of time. Functionally and morphologically, these sensory synapses are unique: their active zones are specialized in several ways for sustained, rapid vesicle exocytosis, but their most striking feature is an organelle called the synaptic ribbon, which is a proteinaceous structure that extends into the cytoplasm at the active zone and tethers a large pool of releasable vesicles. But precisely how does the ribbon function to support tonic release at these synapses? Recent genetic and biophysical advances have begun to open the 'black box' of the synaptic ribbon with some surprising findings and promise to resolve its function in vision and hearing.
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Acknowledgements
The authors are supported by the National Institutes of Health (National Eye Institute grant R01EY003821 to G.M.) and the National Institute on Deafness and other Communication Disorders (grants R01DC000276, R01DC001508 and P30 DC005211 to P.F.)
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Glossary
- Freeze-fracture
-
A technique for 'three-dimensional' imaging of cellular ultrastructure by coating the surface of fractured tissue with electron-dense material.
- SNARE
-
Soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein (SNAP) receptor.
- ON bipolar cell
-
Bipolar cells are classed as either ON or OFF depending on how they respond to glutamate released in their vicinity by photoreceptors. ON bipolar cells respond to a lowering of released glutamate by depolarizing, and OFF bipolar cells respond to this change by becoming hyperpolarized.
- Tonotopic
-
The mapping of tones of different frequencies onto space along a receptive surface, such as the mammalian cochlea, or onto different spatial locations within a brain nucleus that processes auditory information.
- Capacitance
-
Electrical measure of charge-storing capacity. Cell membranes behave as electrical capacitors because the insulating lipid separates two electrically conductive salt solutions. The capacitance of a cell is proportional to the cell's surface area and thus serves as an index of membrane addition and retrieval.
- Cytomatrix at the active zone
-
The complex of membrane-associated and cytoplasmic proteins that provide structural organization for the many components required to dock, prime and fuse synaptic vesicles at presynaptic active zones.
- Pleiomorphic
-
Varied in shape.
- Voltage-clamp
-
A fundamental electrophysiological technique for measuring ionic currents in cells while 'clamping' the membrane potential to prevent changes caused by those currents.
- 'Mini'
-
Shorthand for miniature postsynaptic current, which is the current produced by spontaneous or evoked exocytosis of a single synaptic vesicle.
- Cable loss
-
The decrement of 'passive' voltage signals along neuronal processes.
- Phase-locking
-
Precise timing between two signals. In the auditory system, phase-locking refers to coordination between action potentials in auditory neurons, and the cycles of a tonal stimulus.
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Matthews, G., Fuchs, P. The diverse roles of ribbon synapses in sensory neurotransmission. Nat Rev Neurosci 11, 812–822 (2010). https://doi.org/10.1038/nrn2924
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DOI: https://doi.org/10.1038/nrn2924
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