Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life

Abstract

Before hearing onset, inner hair cell (IHC) maturation proceeds under the influence of spontaneous Ca2+ action potentials (APs). The temporal signature of the IHC Ca2+ AP is modified through an efferent cholinergic feedback from the medial olivocochlear bundle (MOC) and drives the IHC pre- and post-synapse phenotype towards low spontaneous (spike) rate (SR), high-threshold characteristics. With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics. Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step. In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system. In particular, we examine several IHC synaptopathies in the context of various hearing disorders and exemplified shortfalls before and after hearing onset.

Gαi Proteins are Indispensable for Hearing

“…6F). BK channels carry I K,f currents that are essential to transform immature IHCs (exhibiting spontaneous Ca 2+ -spikes) to mature functional cells that are then able to respond to sound [57,58]. Gnai3 cKO IHCs innervated by VAMP 2 positive efferent nerves mature normally, i.e.…”

“…on pruning of connected fibers. Accordingly a timely elimination of axosomatic efferent contacts [54][55][56], coincides with the initiation of biophysical maturation in IHCs [79] (see for a review [58]). Myosin 6 mutants show not only a defective structural integrity of the hair bundle but also an impaired post-hearing IHC maturation that includes the failure to properly target BK channels [80,81], similar to Gnai2/i3 cKO.…”

Variable Effects of Acoustic Trauma on Behavioral and Neural Correlates of Tinnitus In Individual Animals

“…In most clinical cases, there is a strong correlation between hearing loss and tinnitus (Lockwood et al, 2002), but interestingly, this is not always true, as some patients with clinically normal thresholds have tinnitus (Weisz et al, 2006; Job et al, 2007). Just as in humans (Hall et al, 2016), the extent of peripheral damage and central plasticity in individual animals of the AOE model differs greatly, leading to a heterogeneous population of hearing loss (HL) and/or tinnitus pathology (Longenecker and Galazyuk, 2011; Singer et al, 2013; Hickox and Liberman, 2014; Knipper et al, 2015). …”

Biomarkers for Hearing Dysfunction: Facts and Outlook

“…This will enable to compare activity patterns with sound using fMRI technology for animal and human subjects that suffer from the same specific hearing disorders. Examples are tinnitus and hyperacusis that in behavioral animal models can be subclassified through several characteristic functional and molecular fingerprints [21,22,108,109] . Here, future fMRI studies performed in equally hearing-impaired subjects and behaviorally trained animals with and without tinnitus could identify differences in the characteristic connectome and activity pattern between affected and nonaffected species previously impossible to identify.…”