Synaptic Ribbon Enables Temporal Precision of Hair Cell Afferent Synapse by Increasing the Number of Readily Releasable Vesicles: A Modeling Study

Abstract

Wittig JH Jr, Parsons TD. Synaptic ribbon enables temporal precision of hair cell afferent synapse by increasing the number of readily releasable vesicles: a modeling study. J Neurophysiol 100: 1724 -1739, 2008. First published July 30, 2008 doi:10.1152/jn.90322.2008. Synaptic ribbons are classically associated with mediating indefatigable neurotransmitter release by sensory neurons that encode persistent stimuli. Yet when hair cells lack anchored ribbons, the temporal precision of vesicle fusion and auditory nerve discharges are degraded. A rarified statistical model predicted increasing precision of first-exocytosis latency with the number of readily releasable vesicles. We developed an experimentally constrained biophysical model to test the hypothesis that ribbons enable temporally precise exocytosis by increasing the readily releasable pool size. Simulations of calcium influx, buffered calcium diffusion, and synaptic vesicle exocytosis were stochastic (Monte Carlo) and yielded spatiotemporal distributions of vesicle fusion consistent with experimental measurements of exocytosis magnitude and first-spike latency of nerve fibers. No single vesicle could drive the auditory nerve with requisite precision, indicating a requirement for multiple readily releasable vesicles. However, plasmalemma-docked vesicles alone did not account for the nerve's precision-the synaptic ribbon was required to retain a pool of readily releasable vesicles sufficiently large to statistically ensure first-exocytosis latency was both short and reproducible. The model predicted that at least 16 readily releasable vesicles were necessary to match the nerve's precision and provided insight into interspecies differences in synaptic anatomy and physiology. We confirmed that ribbon-associated vesicles were required in disparate calcium buffer conditions, irrespective of the number of vesicles required to trigger an action potential. We conclude that one of the simplest functions ascribable to the ribbon-the ability to hold docked vesicles at an active zone-accounts for the synapse's temporal precision.

Exocytosis in the Frog Amphibian Papilla

“…This indicates that at each synaptic site the fast pool of caudal hair cells is about three times larger (11 vesicles) than the fast pool of rostral hair cells (four vesicles). The larger fast pool implies that caudal hair cells have increased temporal precision of exocytosis (Wittig and Parsons 2008) and achieve greater accuracy of postsynaptic spiking (Buran et al 2010). Our data are thus consistent with the hypothesis that the high-frequency caudal hair cells are capable of transmitting signals with higher temporal precision than the low-frequency rostral hair cells.…”

Disruption of the Presynaptic Cytomatrix Protein Bassoon Degrades Ribbon Anchorage, Multiquantal Release, and Sound Encoding at the Hair Cell Afferent Synapse

“…Therefore, the ribbon and/or functional bassoon seem to be supportive of, but not indispensable for, MQR. The smaller RRP in Bsn ⌬Ex4/5 IHCs results in a longer and more variable first exocytosis latency Wittig and Parsons, 2008;Buran et al, 2010) and a smaller EPSC size, which is expected to further slow and time vary postsynaptic spike generation (Rutherford et al, 2012). Both mechanisms explain the longer and more variable SGN first spike latency in vivo in Bsn ⌬Ex4/5 mice (Buran et al, 2010).…”

Specialized Postsynaptic Morphology Enhances Neurotransmitter Dilution and High-Frequency Signaling at an Auditory Synapse

“…Indeed, bassoon KO-mice that lack synaptic ribbons have greatly reduced exocytosis, longer first-spike latencies, and pronounced jitter in spike timing (Buran et al, 2010). The larger readily releasable pool afforded by multiple synaptic ribbons connected to one afferent fiber should therefore shorten the onset timing of spikes and enhance the precision of sound onset encoding (Wittig and Parsons, 2008). Several species (e.g., fish, amphibians, reptiles, turtles, and birds) display auditory afferent fibers that are connected to several synaptic ribbons (Martinez-Dunst et al, 1997), whereas mammals appear to be a notable exception.…”