Fine-Tuning an Auditory Synapse for Speed and Fidelity: Developmental Changes in Presynaptic Waveform, EPSC Kinetics, and Synaptic Plasticity

TLDR

Fast, precise, and sustained synaptic transmission at high frequency is essential for sound localization in the auditory brainstem. The study investigates how the calyx of Held synapse refines its function from postnatal day 5 to the onset of hearing (P12–P14). This refinement is driven partly by a shortening of presynaptic action potentials, which lowers release probability and reduces synaptic delays. Recordings show that by P14 the synapse can sustain 800 Hz stimulation, with AMPA EPSCs and quantal currents gaining faster kinetics, NMDA EPSCs reduced by half, and synaptic depression markedly diminished due to a larger releasable vesicle pool and lower release probability, thereby preserving speed while preventing vesicle depletion.

Abstract

Fast, precise, and sustained synaptic transmission at high frequency is thought to be crucial for the task of sound localization in the auditory brainstem. However, recordings from the calyx of Held synapse have revealed severe frequency-dependent synaptic depression, which tends to degrade the exact timing of postsynaptic spikes. Here we investigate the functional changes occurring throughout the critical period of synapse refinement from immature calyx terminal [postnatal day 5 (P5)] to after the onset of hearing (P12–P14). Surprisingly, for recordings near physiological temperature (35°C), we find that P14 synapses are already able to follow extremely high input rates of up to 800 Hz. This ability stems in part from a remarkable shortening of presynaptic action potentials, which may lead to a lowering of release probability and decrease in synaptic delays during development. In addition, AMPA receptor-mediated EPSCs as well as quantal synaptic currents acquired progressively faster kinetics, although their mean amplitudes did not change significantly. NMDA receptor-mediated EPSCs, however, diminished with age, as indicated by a 50% reduction in mean amplitude and faster decay kinetics. Finally, the degree of synaptic depression was greatly attenuated with age, presumably because of a 2.5-fold or larger increase in the releasable pool of vesicles, which together with a decreasing release probability produces a fairly constant EPSC amplitude. This finely tuned orchestra of developmental changes thus simultaneously promotes speed while preventing premature vesicle pool depletion during prolonged bouts of firing. A few critical days in postnatal development can thus have a large impact on synaptic function.