Developmental changes in calcium domain at the presynaptic terminal of the central synapse

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The Ca domain in presynaptic nerve terminal can determine speed and fidelity of synaptic transmission. At the calyx of Held, in the rat auditory brainstem, intraterminal injection of EGTA attenuates EPSC amplitude before hearing onset postnatal day (P)7). But this inhibitory effect is almost negligible after hearing onset (P14), implying that Ca domain is developmentally transformed from microdomain into nanodomain. To visualize Ca domain in the nerve terminal, I employed a localized confocal spot detection method and a low affinity Ca^<2+> indicator Oregon Green BAPTA/5N, to assess the spatiotemporal profile of single action potential (AP)-evoked Ca^<2+> gradients in P7 and P14 terminals. Ca transient were observed in almost every confocal spot locations along synaptic surface at P7, but they were less frequently observed and their amplitude became smaller at P14. Voltage-clamp experiments revealed that both shortening of presynaptic action potential and decrease in Ca channel density contribute to this reduction in Catransients. To investigate these two mechanisms underlie developmental changes in Ca domain, I performed simultaneous pre^- and postsynaptic electrophysiological recordings. Reducing the number of functional Ca channels in P7 terminals with peptide Ca^<2+> channel blockers markedly reduced the inhibitory effect of intraterminal EGTA injection on EPSCs. Conversely, at P13-15 synapses, prolongation of AP duration using TEA increased the effect of EGTA on EPSCs. We conclude that both the developmental decreases in Ca^<2+> channel density and AP duration contribute to developmental transformation of Ca domain at the calyx of Held synapse, through a decrease in the density of open channels.