Tackling the Dynamic Range Problem of Hearing: Diverse Hair Cell Synapses Enable Broad Neural Sound Intensity Coding

Abstract

Synaptic heterogeneity can expand the encoding capacity of individual neurons or sensory cells. The afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea exhibit marked heterogeneity in structure and function. Synapses at the modiolar IHC-side have larger active zones and Ca 2+ -channel clusters, yet their activation requires stronger depolarization. SGNs differ in their spontaneous activity and sound threshold. However, the connection between synaptic heterogeneity and neural response diversity has remained elusive. Here, we bridged this gap by ex-vivo paired recordings of IHCs and postsynaptic boutons with stimuli and conditions aimed to mimic those of in-vivo SGN-characterization. We find that the spontaneous rate ( SR ) of synaptic transmission depends on synapse position. High SR synapses predominantly localize to the pillar IHC-side, larger spontaneous EPSCs, lower voltage-thresholds, shorter response latencies and stronger initial release rates. This study reveals that presynaptic heterogeneity in IHCs translates into diverse SGN properties.

Funding Information: This work was further supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) via the Collaborative Research Center 889 (project A02) and the Leibniz Program (MO896/5 to T.M). This research was further supported by Fondation Pour l’Audition (FPA RD-2020-10). LMJT is a member of the Hertha Sponer College from the Cluster of Excellence Multiscale Bioimaging (MBExC).

Declaration of Interests: The authors declare that no competing interests exist.

Ethics Approval Statement: The animal handling and experiments complied with national animal care guidelines and were approved by the University of Göttingen Board for animal welfare and the Animal Welfare Office of the State of Lower Saxony.

Keywords: paired recordings, synaptic heterogeneity, sound intensity coding, active zone, Synaptic Vesicle