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

Marlies Knipper,Rama Panford-Walsh,Wibke Singer,Ulrike Zimmermann,Lukas Rüttiger

doi:10.1007/s00441-015-2168-x

Marlies Knipper, Rama Panford-Walsh + Show 3 more

Open Access

https://doi.org/10.1007/s00441-015-2168-x

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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.

Highlights

During maturation of the first synapse of the auditory system at the inner hair cell (IHC) synapse onto auditory nerve (AN) fibers, huge modifications in electrical and morphological properties occur
The improved Ca2+ efficiency of IHC exocytosis might rather be a maturation step of the IHC synapse, which is initiated through the elimination of transient axosomatic efferent fibers and the termination of Ca2+ action potentials (APs) firing under the control of Thyroid hormone (TH)
excitatory post-synaptic currents (EPSCs) are multiphasic, resulting from uncoordinated multivesicular release (Glowatzki and Fuchs 2002). These multiphasic EPSCs are postulated to occur in response to transmitter release from larger elongated ribbons located at the modiolar side of IHCs (Liberman et al 2011; Yin et al 2014; Fig. 1b, left)

Summary

Introduction

During maturation of the first synapse of the auditory system at the inner hair cell (IHC) synapse onto auditory nerve (AN) fibers, huge modifications in electrical and morphological properties occur. Spontaneous Ca2+ APs of IHCs are modified by olivocochlear efferent fibers projecting from the ventromedial aspects of superior olivary complex anlage to the cochlea (MOC fibers), where they Bwait^ under the IHC region before targeting the outer hair cells (OHCs; for a review, see Simmons 2002). They remain in axosomatic contact with IHCs until they are eliminated and IHCs are innervated mainly by afferent fibers, having few, if any, remaining efferent contacts (Liberman et al 1990). Ca2+ AP firing (Brandt et al 2007) and axosomatic cholinergic inputs (Sendin et al 2007) persist in the absence of TH, meaning that neither the cholinergic input, nor the spontaneous APs per se, nor their combined activity are the trigger for the improved Ca2+ efficiency of the IHC exocytosis

Conclusion

Conclusion and open questions

Findings

Concluding remarks and future perspectives