Bridging the gap between presynaptic hair cell function and neural sound encoding

Abstract

Neural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca2+-channels. The postsynaptic SGNs differ in their spontaneous firing rates, sound thresholds and operating ranges. While a causal relationship between synaptic heterogeneity and neural response diversity seems likely, experimental evidence linking synaptic and SGN physiology has remained difficult to obtain. Here, we aimed at bridging this gap by ex vivo paired recordings of IHCs and postsynaptic SGN boutons with stimuli and conditions aimed to mimic those of in vivo SGN-characterization. Synapses with high spontaneous rate of release (SR) were found predominantly on the pillar side of the IHC. These high SR synapses had larger and more temporally compact spontaneous EPSCs, lower voltage-thresholds, tighter coupling of Ca2+ channels and vesicular release sites, shorter response latencies and higher initial release rates. This study indicates that synaptic heterogeneity in IHCs directly contributes to the diversity of spontaneous and sound-evoked firing of SGNs. Significance StatementSound encoding relies on spiral ganglion neurons (SGNs) with diverse spontaneous firing, sound thresholds of firing and sound-intensity range over which SGN firing rate changes. Such functional SGN diversity might originate from different input from afferent synapses with inner hair cells (IHCs). The present study addresses this hypothesis by using recordings from individual IHC-SGN synapses of hearing mice under ex vivo conditions aimed to mimic cochlear physiology. The results provide evidence that synaptic heterogeneity in IHCs contributes to SGN firing diversity. Thus, the cochlea employs heterogeneous synapses to decompose sound information into different neural pathways that collectively inform the brain about sound intensity.