Postnatal maturation of auditory-nerve heterogeneity, as seen in spatial gradients of synapse morphology in the inner hair cell area

Abstract

Auditory nerve fibers in the adult ear are divided into functional subgroups according to spontaneous rate (SR) and threshold sensitivity. The high-threshold, low-SR fibers are morphologically and spatially distinct from the low-threshold high-SR fibers at their synaptic contacts with inner hair cells. This distinction between SR groups in the adult ear is visible in confocal microscopy as complementary size gradients of presynaptic ribbons and post-synaptic glutamate receptor patches across the modiolar-pillar and habenular-cuticular axes in the inner hair cell area. The aim of the present study was to track the post-natal development of this morphological gradient, in mouse, to determine the earliest age at which this important aspect of cochlear organization is fully mature. Here we show, using morphometric analysis of the organ of Corti immunostained for pre- and post-synaptic markers of efferent and afferent innervation, that this SR-based morphological gradient is not fully established until postnatal day 28, well after other features, such as synaptic counts and efferent innervation density in both the inner and outer hair cell areas, appear fully mature.

Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System

“…The onset of hearing in mice does not occur until P12-P14 (Ehret, 1983; Mikaelian and Ruben, 1965) and synapse formation between SGNs and hair cells progresses up to P28 (Fig. 4A) (Huang et al, 2012; Liberman and Liberman, 2016; Sobkowicz et al, 1986). We therefore immunostained sections of the inner ear between P0 and P28 with markers for SGN subtypes…”

“…Refinement of SGN subtypes continues into the fourth week after birth, thus extending into the time of active hearing, suggesting that sensory input driven events also participate in SGN specification. Maturation of ribbon synapses continues until the fourth postnatal week (Huang et al, 2012; Liberman and Liberman, 2016; Sobkowicz et al, 1986). This time-frame also overlaps with the period when murine SGNs refine their firing properties from an immature state to a range of fibers differing in their SRs (Wu et al, 2016), indicating an intriguing interplay between molecular and functional diversification.…”

A dual‐AAV approach restores fast exocytosis and partially rescues auditory function in deaf otoferlin knock‐out mice

“…In rodents, SGNs diversify in the first four postnatal weeks into low, medium, and high spontaneous rate fibers to encode different sound intensities (Liberman & Liberman, 2016). In mature Vglut3 À/À mice lacking~40% of SGNs (Seal et al, 2008), almost all low spontaneous rate fibers and half of the medium rate fibers are missing (Shrestha et al, 2018).…”

Hair Cell Afferent Synapses: Function and Dysfunction

“…During the same period, the number of presynaptic ribbons decreases (Sobkowicz et al 1986;Sendin et al 2007;Huang et al 2012) as a consequence of the pruning of type I SGN branches (for review, see Pujol et al 1998), such that in the mature cochlea, type I SGNs form one-to-one axosomatic contact with a given IHC ( Fig. 3) (Kujawa and Liberman 2009;Meyer et al 2009;Liberman and Liberman 2016). After the onset of hearing, Ca 2+ channels cluster beneath the ribbon within the IHC pre-synaptic active zones, resulting in a tighter spatial coupling between Ca 2+ influx and exocytosis at mature synapses (e.g., Wong et al 2014;Neef et al 2018).…”