Key Points
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The mechanisms that underlie short-term synaptic plasticity are beginning to be understood. Modifications of the pre- or the postsynaptic elements can account for transient changes in the efficacy of synapses, but presynaptic changes have been particularly difficult to document, owing to the small size of the axon terminal. The calyx of Held — a synapse of the auditory brainstem — has been a good model for the study of presynaptic mechanisms of plasticity, chiefly because of its large size, which makes it accessible to direct experimental manipulations.
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The calyx of Held undergoes marked morphological and physiological changes during development. They take place both pre- and postsynaptically, and allow this synaptic contact to be extraordinarily fast and reliable. The calyx of Held is involved in sound localization, and its speed is crucial for the accuracy required in performing this function.
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Although calcium-dependent, short-term facilitation has been observed at the calyx of Held, most experimental attention has centred on the mechanisms of short-term depression. Pre- and postsynaptic mechanisms have been proposed to explain depression; their relative contributions depend on the frequency of stimulation.
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Possible presynaptic mechanisms of depression at the calyx of Held include changes in action potential waveform, inactivation of calcium currents and vesicle pool depletion. The evidence favours the idea that pool depletion is the most prominent mechanism at this synaptic contact. Glutamate receptor saturation has been proposed, in turn, as a possible postsynaptic mechanism of depression, although the evidence indicates that receptor desensitization has a more significant role.
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Although short-term plasticity is prominent at the calyx of Held, its relevance to signal processing is unclear. Also, many related questions remain unanswered. How plastic is this synapse in adult animals? How much can the conclusions obtained in the calyx be extrapolated to bouton-type synapses? What mechanisms modulate and control the kinetics of vesicle recycling? The experimental advantages that the calyx of Held offers will be instrumental in solving these riddles.
Abstract
Synapses show widely varying degrees of short-term facilitation and depression. Several mechanisms have been proposed to underlie short-term plasticity, but the contributions of presynaptic mechanisms have been particularly difficult to study because of the small size of synaptic boutons in the mammalian brain. Here we review the functional properties of the calyx of Held, a giant nerve terminal that has shed new light on the general mechanisms that control short-term plasticity. The calyx of Held has also provided fresh insights into the strategies used by synapses to extend their dynamic range of operation and preserve the timing of sensory stimuli.
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DATABASES
FURTHER INFORMATION
calcium and neurotransmitter release
developmental biology of synapse formation
glutamatergic synapses: molecular organization
Glossary
- ACTIVE ZONE
-
A portion of the presynaptic membrane that faces the postsynaptic density across the synaptic cleft. It constitutes the site of synaptic vesicle clustering, docking and transmitter release.
- QUANTAL CONTENT
-
The number of quanta — unitary packets of transmitter — released per action potential.
- GAP JUNCTIONS
-
Cellular specializations that allow the non-selective passage of small molecules between the cytoplasm of adjacent cells. They are formed by channels termed connexons, multimeric complexes of proteins known as connexins. Gap junctions are structural elements of electrical synapses.
- POSTSYNAPTIC DENSITY
-
An electron-dense thickening underneath the postsynaptic membrane at excitatory synapses that contains receptors, structural proteins linked to the actin cytoskeleton and signalling machinery, such as protein kinases and phosphatases.
- PRESPIKE
-
The presynaptic action potential capacitatively coupled to the postsynaptic cell.
- PHASE-LOCKING
-
The firing of neurons preferentially at a certain phase of an amplitude-modulated stimulus.
- ELECTROTONIC DISTANCE
-
The anatomical distance between a channel or a synapse and the recording site, divided by the length constant (the distance at which signal amplitude decreases to 37% of its original size).
- FILOPODIA
-
Long, thin protrusions at the periphery of cells and growth cones. They are composed of F-actin bundles.
- FLOP VARIANT OF AMPA RECEPTOR
-
Two splice variants of AMPA receptor, known as flip and flop, have been characterized. They differ in their response to glutamate, their distribution and their developmental expression.
- QUANTAL SIZE
-
The synaptic response elicited by a single vesicle of transmitter.
- DELAYED RELEASE
-
A period of elevated spontaneous quantal release following an action potential.
- CAPACITANCE
-
The plasma membrane is an excellent insulator and can store electrical charge on its surface. Capacitance is the quantity of charge that must be moved across a unit area of the membrane to produce a unit change in membrane potential. Most plasma membranes have a capacitance of around 1 μF cm−2. As synaptic vesicle fusion increases membrane area, an increase in capacitance can be interpreted as a measure of exocytosis.
- SYNAPTOSOME
-
A preparation of the presynaptic terminal, isolated after subcellular fractionation. This structure retains the anatomical integrity of the terminal and can take up, store and release neurotransmitters.
- RIBBON SYNAPSE
-
Synapses characterized by an electron-dense ribbon or bar in the presynaptic terminal. The ribbon is commonly oriented at a right angle to the membrane and sits just above an evaginated ridge. It is thought that the ribbons help to guide vesicles to the release sites. Ribbon synapses are commonly found in the retina and cochlea of vertebrates.
- SHIBIRE MUTANT
-
Shibire is the Drosophila homologue of dynamin. Accordingly, the shibire mutant shows defects in the recycling of synaptic vesicles.
- DYNAMIN
-
A GTPase that takes part in endocytosis. It seems to be involved in severing the connection between the nascent vesicle and the donor membrane.
- NON-STATIONARY NOISE-ANALYSIS METHODS
-
Methods that make use of fluctuations in biological signals that vary in time to derive information about the underlying elementary events. Such methods can be used, for example, to derive single ion channel current and number from the variance of macroscopic currents.
- CAGED COMPOUNDS
-
Inactive derivatives of biologically functional molecules, which can be transformed into the active compound, usually by photolysis of the precursor.
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von Gersdorff, H., Borst, J. Short-term plasticity at the calyx of held. Nat Rev Neurosci 3, 53–64 (2002). https://doi.org/10.1038/nrn705
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DOI: https://doi.org/10.1038/nrn705
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