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Review
, 2, 36

Action Potential Evoked Transmitter Release in Central Synapses: Insights From the Developing Calyx of Held

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Review

Action Potential Evoked Transmitter Release in Central Synapses: Insights From the Developing Calyx of Held

Lu-Yang Wang et al. Mol Brain.

Abstract

Chemical synapses are the fundamental units that mediate communication between neurons in the mammalian brain. In contrast to the enormous progress made in mapping out postsynaptic contributions of receptors, scaffolding structures and receptor trafficking to synaptic transmission and plasticity, the small size of nerve terminals has largely precluded direct analyses of presynaptic modulation of excitability and transmitter release in central synapses. Recent studies performed in accessible synapses such as the calyx of Held, a giant axosomatic synapse in the sound localization circuit of the auditory brainstem, have provided tremendous insights into how central synapses regulate the dynamic gain range of synaptic transmission. This review will highlight experimental evidence that resolves several long-standing issues with respect to intricate interplays between the waveform of action potentials, Ca2+ currents and transmitter release and further conceptualize their relationships in a physiological context with theoretical models of the spatial organization of voltage-gated Ca2+ channels and synaptic vesicles at release sites.

Figures

Figure 1
Figure 1
Linearized Buffered Diffusion & Release Site Topography Model. (A) Schematic representation of the single VGCC for which the buffered diffusion model determines [Ca2+] as a function of r. (B) [Ca2+] as a function of r for the various buffer conditions from Fedchyshyn & Wang (2005) in response to the steady-state opening of a single VGCC. (C) [Ca2+]·r as a function of r, or the buffer composition "fingerprint" for the various buffer conditions from Fedchyshyn & Wang (2005) in response to the steady-state opening of a single VGCC. (D) Modeled arrangement of VGCCs in immature (magenta VGCCs) and mature (cyan VGCCs) synapses. ENDO refers to endogenous immobile buffer. Single VGCC flux for all panels F = 6.24 × 105 ions/sec or 0.2pA of constant current. Buffer parameters are as in Naraghi & Neher (1997). Schematics are not drawn to scale.
Figure 2
Figure 2
Summary of developmental changes in the temporal profiles of the local [Ca2+]i transient seen by the Ca2+ sensor and glutamate release during an AP. A, Schematic diagram illustrating developmental tightening in the coupling between synaptic vesicles and VGCCs. Immature calyces (A1) have fewer docked vesicles that are loosely coupled to VGCCs, whereas mature calyces (A2) possess approximately a twofold larger number of release-competent vesicles that more closely colocalize with Ca2+ channels. B, Timing (right) of the local [Ca2+]i (red) and release (blue) transients relative to the presynaptic APs (black) for P9--P11 (B1) and P16--P19 (B2) calyces. Traces in B1 and B2 were aligned relative to the onset of the presynaptic APs (dotted line). The average time course of the AP-evoked local [Ca2+]i transients was obtained from 16 of P9--P11 and 18 of P16--P19 synapses. The peak of the local [Ca2+]i transient occurred ~410 μs earlier in mature synapses, because of their faster and briefer presynaptic APs (Image © Wang et al., 2008).

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