Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

Abstract

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca 2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca 2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca 2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca 2+ channels expands at the expense of vesicles more distant from Ca 2+ channels.

The Coupling between Ca2+Channels and the Exocytotic Ca2+Sensor at Hair Cell Ribbon Synapses Varies Tonotopically along the Mature Cochlea

“…However, recent findings have shown that mature hippocampal synapses can also operate via a loose coupling (Vyleta and Jonas, 2014), challenging the view that Ca 2+ -microdomain mode of Ca 2+ signaling is only a characteristic of immature synapses (e.g., Meinrenken et al, 2002; Fedchyshyn and Wang, 2005; Leão and von Gersdorff, 2009; Wang and Augustine, 2015). Instead, it suggests that the vesicle release modality is optimized for specific functional requirements independent from the stage of cell maturation.…”

The Calyx of Held Develops Adult-Like Dynamics and Reliability by Hearing Onset in the MouseIn Vivo

“…In hearing animals, STD was not observed anymore (Lorteije et al, 2009) and, also, transmission failures were rare, suggesting that STD is of little relevance in hearing animals, at least during spontaneous activity. The underlying physiological conditions are the adult-like size of readily releasable vesicle pools, a sufficient exocytosis efficiency, and the reduced release probability compensated by tighter coupling of vesicles to calcium channels (Taschenberger and von Gersdorff, 2000;Futai et al, 2001;Iwasaki and Takahashi, 2001;Joshi and Wang, 2002;Taschenberger et al, 2002;Fedchyshyn and Wang, 2005;Yang and Wang, 2006;Wang et al, 2008;Kochubey et al, 2009;Leão and von Gersdorff, 2009). The transmission delay and the amplitude of the postsynaptic AP also underlie strong activity-dependent plasticity in prehearing mice and, to a lesser extent, also in hearing animals.…”

Exocytotic dynamics and calcium cooperativity effects in the calyx of Held synapse: a modelling study

“…These numbers correspond to an estimated average number of calcium channels and docked vesicles (from a ready-releasable pool) for an active zone of juvenile calyx of Held synapses (Sãtzler et al 2002;Meinrenken et al 2003), which correspond to the type of calyces used in the experiments of Sakaba and Neher (2001a, b). However, the estimation of the number of docked vesicles as well as the corresponding to the number of active zones of the calyx, seems to increase as the calyx matures; this fact suggests a tighter spatial coupling between channels and synaptic vesicles in mature calyces (and/or a change in the kinetic constants of the release sensor) which result in a increased efficiency for exocytosis for mature calyces (Taschenberger et al 2002;Fedchyshyn and Wang 2005;Wang et al 2008;Leao and von Gersdorff 2009). Therefore, model parameters of our computational scheme like vesicle or channel population and spatial arrangements could be varied to simulate experiments on older calyces.…”

“…The reason of this is that the high calcium currents induced by the 0 mV pulse, provoke a fast local buffer saturation, reducing, in this way, the effectiveness of BAPTA in blocking secretion. From an experimental point of view, the effect of exogenous buffers on the exocytotic response seems also to vary depending on the stage of maturation of the calyx, as discussed and analyzed in detail in Leao and von Gersdorff (2009), being the probability of local buffer saturation greater in mature terminals. This fact also supports a higher degree of organization in older calyces which, as we will point out in the next section, could have a measurable influence on estimations of the kinetic cooperativity for secretion.…”