Donut-Like Topology of Synaptic Vesicles with a Central Cluster of Mitochondria Wrapped into Membrane Protrusions: A Novel Structure–Function Module of the Adult Calyx of Held

Abstract

Structural and functional properties of synapses are intricately and reciprocally coupled. To cope with the functional requirements in auditory processing, the calyx of Held developed distinct structural specializations such as a large number of active zones, large size, elaborate morphology, and defined distribution of ion channels. These specializations typically appear during postnatal maturation within the first 3 weeks of life and are accompanied by marked changes in the properties of synaptic transmission. We examined the arrangement of synaptic vesicles at different postnatal stages of maturation by genetically labeling vesicles with the fluorescent fusion protein synaptophysin-enhanced green fluorescent protein. Fluorescence and electron microscopy-based analyses revealed a new anatomical specialization in the mature calyx of Held. Within small, membrane-delimited compartments (swellings), synaptic vesicles formed donut-like assemblies around a central cluster of interconnected mitochondria. Adult calyces contained ϳ100 such structural units, each of them consisting of ϳ800 synaptic vesicles, six to nine mitochondria, and five to nine active zones. A donut of synaptic vesicles measured ϳ1 m in diameter and was placed in a swelling with a volume of ϳ5 fl. Conspicuously, this structural specialization appears with the onset of hearing and may contribute to maturational changes in presynaptic function.

A comparison between exocytic control mechanisms in adrenal chromaffin cells and a glutamatergic synapse

“…A possible reason for this difference may reside in the fact that nerve terminals have very specialized active zones with well-defined binding sites for vesicles [37,38], whereas adrenaline release from chromaffin cells can occur throughout the cell surface. Active zones may change in shape and number over a long time scale [39], but within the short time span of our experiments the number of specialized docking sites for vesicles are expected to be relatively constant. The existence of specialized active zones with high Ca ++ channel density, combined with the morphological finding that vesicles also dock at some distance from them, may be a reason for kinetic heterogeneity in the depolarization experiments, which is not relevant in our caged Ca ++ experiments on adrenal chromaffin cells.…”

Mechanisms of Prolonged Presynaptic Ca2+Signaling and Glutamate Release Induced by TRPV1 Activation in Rat Sensory Neurons

“…Although CPA modulates electrically evoked [Ca 2ϩ ] i transients in DRG neurons (Usachev and Thayer, 1999;Lu et al, 2006), capsaicin-induced presynaptic [Ca 2ϩ ] i plateau was not significantly affected by the drug (Fig. 5D) (Zucker and Regehr, 2002;Hollenbeck, 2005;Wimmer et al, 2006). The function and mechanisms of Ca 2ϩ transport by presynaptic mitochondria vary substantially among synapses and are likely specialized according to the signaling needs at a particular synapse (Tang and Zucker, 1997;Billups and Forsythe, 2002;Jonas et al, 2003;Levy et al, 2003;Yang et al, 2003;Garcia-Chacon et al, 2006).…”

Morphological and Functional Continuum Underlying Heterogeneity in the Spiking Fidelity at the Calyx of Held SynapseIn Vitro

“…However, at ages when the calyx of Held-MNTB synapse is considered functionally mature (ϾP14), calyx terminals exhibit variability in subcellular parameters such as the size and number of active zones as well as gross morphological features such as surface area and volume (Taschenberger et al, 2002;Wimmer et al, 2006;Youssoufian et al, 2008;Dondzillo et al, 2010;Schwenger and Kuner, 2010). Thus, it is possible that some principal MNTB neurons are innervated by calyx terminals with unique structural characteristics.…”

“…At P16 -P19, calyces were digitated structures containing fenestrations, stalks, and elliptical swellings emanating from the stalks via a thin neck (Fig. 3B) typical of mature calyces in many species (Kandler and Friauf, 1993;Rowland et al, 2000;Wimmer et al, 2006;Ford et al, 2009;Dondzillo et al, 2010;Hermida et al, 2010). However, after 3D rendering, it became immediately apparent that calyces of Held were morphologically heterogeneous.…”

“…At mature ages (ϾP14), the calyx of Held-MNTB expresses varying degrees of short-term depression (STD) and facilitation (STF) under both in vitro-and in vivo-like conditions (Taschenberger and von Gersdorff, 2000;Hermann et al, 2007;Müller et al, 2010). Furthermore, mature calyces of Held display variability in several anatomical specializations (Rowland et al, 2000;Felmy and Schneggenburger, 2004;Wimmer et al, 2006;Ford et al, 2009;Dondzillo et al, 2010). We asked whether the success or failure rate of excitatory input coupling to principal MNTB neuron spiking relates to heterogeneities in short-term plasticity (STP) and calyx terminal morphology.…”