Authors
Karagulyan N, Überegger M, Qi Y, Babai N, Hofer F, Johnson Chacko L, Wang F, Luque M, Glueckert R, Schrott-Fischer A, Hua Y, Moser T, Bandtlow C
Journal
BioRxiv
Citation
bioRxiv 2024.09.16.613011.
Abstract
Sound encoding depends on the precise and reliable neurotransmission at the afferent synapses between the sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs). The molecular mechanisms contributing to the formation, as well as interplay between the pre-and postsynaptic components remains largely unclear. Here, we tested the role of the Nogo receptor homolog NgR2 (RTN4rl2) in the development and function of afferent IHC-SGN synapses. Upon deletion of NgR2 in mice (NgR2-/-), presynaptic IHC active zones showed enlarged synaptic ribbons and a depolarized shift in the activation of CaV1.3 Ca2+ channels. The postsynaptic densities (PSDs) of SGNs were smaller and deficient of GluA2/3 despite maintained Gria2 mRNA expression in SGNs. Next to synaptically engaged PSDs we observed “orphan” PSDs located away from IHCs. They likely belong to a subset of SGN peripheral neurites that do not contact the IHCs in NgR2-/- cochleae as found by volume electron microscopy reconstruction of SGN neurites. Auditory brainstem responses of NgR2-/- mice showed increased sound thresholds indicating impaired hearing. Together, these findings suggest that NgR2 contributes to the proper formation and function of auditory afferent synapses and is critical for normal hearing.
