Abstract
The early auditory pathway processes information at high rates and with utmost temporal fidelity. Consequently, the synapses in the auditory pathway are highly specialized to meet the extraordinary requirements on signal transmission. The calyceal synapses in the auditory brainstem feature more than a hundred active zones (AZs) with thousands of releasable synaptic vesicles (SVs). In contrast, the first auditory synapse, the afferent synapse of inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs), typically exhibits a single ribbon-type AZ tethering only tens of SVs resulting in a highly stochastic pattern of transmitter release. Spontaneous excitatory postsynaptic currents (sEPSCs), besides more conventional EPSCs with a single peak, fast rise and decay (compact), also include EPSCs with multiple peaks, variable rise and decay times (non-compact). The strong heterogeneity in size and shape of spontaneous EPSCs has led to the hypothesis of multivesicular release (MVR) that is more (compact) or less (non-compact) synchronized by coordination of release sites. Alternatively, univesicular release (UVR), potentially involving glutamate release through a flickering fusion pore for non-compact EPSCs, has been suggested to underlie IHC exocytosis. Here, we further investigated the mode of release by recording sEPSCs from SGNs of hearing rats while manipulating presynaptic IHC Ca2+ influx by changes in extracellular [Ca2+] ([Ca2+]e) and by application of the Ca2+ channel antagonist, isradipine, or the Ca2+ channel agonist, BayK8644 (BayK). Our data reveal that Ca2+ influx manipulation leaves the distributions of sEPSC amplitude and charge largely unchanged. Regardless the type of manipulation, the rate of sEPSC decreased with the reduction in Ca2+ influx. The fraction of compact sEPSCs was increased in the presence of BayK, an effect that was abolished when combined with decreased [Ca2+]e. In conclusion, we propose that UVR is the prevailing mode of exocytosis at cochlear IHCs of hearing rats, whereby the rate of exocytosis and the kinetics of SV fusion are regulated by Ca2+ influx.
Highlights
Established by del Castillo and Katz (1954), the quantal hypothesis of transmitter release has served as a widely accepted model of presynaptic exocytosis
We studied the mode of synaptic vesicles (SVs) release (Figure 1) and its regulation by Ca2+ at the rat inner hair cells (IHCs) synapse after hearing onset by performing whole-cell patch-clamp recordings of Spontaneous excitatory postsynaptic currents (sEPSCs) from the postsynaptic spiral ganglion neurons (SGNs) at postnatal days (P) P17– P19, while manipulating Ca2+ influx in the unclamped IHCs
Mean ± standard error of the mean (SEM) of parameters describing the waveforms of compact and non-compact EPSCs in all experimental conditions is shown in the table
Summary
Established by del Castillo and Katz (1954), the quantal hypothesis of transmitter release has served as a widely accepted model of presynaptic exocytosis. It states that synaptic vesicles (SVs) at the presynaptic active zone (AZ) are released independently of each other, i.e., undergo uniquantal release or univesicular release (UVR), and that neurons primarily regulate the rate at which. Even with vesicles fusing independently from each other, i.e., an univesicular mode of exocytosis, release evoked by an action potential can involve more than one vesicle, said to be multivesicular (Tong and Jahr, 1994). Since this definition is difficult to apply to release at ribbon synapses that is driven by graded potentials rather than action potentials, we resort to the former definition of the mode of release
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