**5. Afferent and efferent innervation**

#### **5.1. Afferent innervation**

grouped in one row, in contrast to about 12000 outer hair cells that are grouped in three rows. 90–95 % of all innervation supplies the inner hair cells and each inner hair cell has contact with

Inner hair cells show a characteristic 'flask' shape, displaying a constriction in the neck region. Relative to the surface of the organ of Corti, the cell body is angled towards the centre of the cochlear spiral (the modiolus) and away from the supporting pillar cell. The apical half of the cell contains the nucleus, and the infranuclear region shows an extensive and seemingly continuous network of intracellular endoplasmic reticulum membranes, associated with mitochondria and cytoplasmic vesicles. The afferent nerve endings form characteristical ribbon synapses around the entire baso-lateral region below the level of the nucleus [42]. Ribbon synapses are specialized for the precision and speed required to process auditory information

The inner hair cells are embedded for stabilization between inner sulcus cells and inner pillar cells, which shape the stiffness and elastic reactance of the travelling wave-processing structures [45]. Already, the basilar membrane and the inner and outer hair cells with their receptor potentials show tuning characteristics similar to the characteristical tuning of the cochlear

The inner ear is not just a mechanoreceptor, but is capable to an active processing by the outer hair cells. The active component can be up to more than 100 times larger than the classical basilar membrane vibration. The outer hair cells enhance and focus the amplitude of the travelling wave by its contractions at sound pressure levels up to 60 dB (cochlear amplification) [47]. But the outer hair cells with their W-pattern-aligned stereocilia are not just a cochlear amplifier; they are three-dimensionally regulators for bone conduction and the natural

To process the sound waves three-dimensionally, the outer hair cells are positioned on Deiters cells. Corresponding to the necessity for continous fast and active response to stimulation, they

The outer hair cells with their micromechanical properties enhance frequency selectivity and the tone intensity range. Stimulus protection, distance adjustment and sharpness enhancement in the eye are executed by the micromechanical light accommodation of the lens and the pupils and the biochemical and electrophysiological light accommodation by variation of the amount of photopigment and the open probability of transduction channels by the photoreceptors.

Hyperpolarization mediated by specific GABAA receptors (gamma aminobutyric acid A) causes expansion of prestin molecules, which elongates the outer hair cell [48]. Stimulation of ACh receptors (acetylcholine) leads to opposite outer hair cell changes [49]. Those outer hair cell changes can be measured as otoacoustic emissions (OAEs, spontaneous and evoked).

Contrastingly to the innervation of inner hair cells, the afferent nerve-receptor cell ratio is with

are surrounded by two endolymph spaces, the outer tunnel and the Nuel space.

about fifteen to twenty neurons, of which about 90 % are afferent neurons [42, 43].

and show tonotopical variation in function and form along the cochlear duct [44].

afferent neurons [46].

214 Advances in Clinical Audiology

**4.3. Outer hair cells**

exposition to bone vibrations.

about 1:10 negative [43, 50].

90–95 % of innervation to the hair cells is afferent, and 90-95 % are bipolar afferent type I neurons, which are organized in the spiral ganglion and form single ribbon synapses under inner hair cells. These specific synapses are found in retinal photoreceptors and bipolar neurons. Outer hair cells are innervated by type II afferent neurons, which are ribbonless and only excited with maximal synaptic stimulation, suggesting to be part of the sensory drive for the medial olivocochlear reflex protecting from acoustic overstimulation [51]. But the majority of outer hair cell innervation is efferent and about 90% of all efferent innervation terminates on outer hair cells [43, 52].

The first neurons of all parts of the vestibulocochlear nerve are truely bipolar, formed to the spiral ganglion in the bony modiolus, and leave the vestibule through the lamina cribrosa, which is a thin bony plate that is penetrated by the neural structures and blood vessels originating in most cases from the anterior inferior cerebellar artery. The lamina cribrosa is medially covered by dura mater and arachnoidea and forms a barrier between the inner ear and the subarachnoid space.

The excitatory afferent transmission of the auditory system is regulated by various types of glutamate receptors, ionotropic glutamate receptors of the N-methyl-d-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type as well as group I and II metabotropic glutamate receptors, and inhibitorily efferent modulated by GABA and dopamine [53].

Complex neural processing between afferent and efferent fibres is found in the spiral ganglion and the ventral cochlear nucleus (VCN) [54]. Not just tonotopical place coding but also periodical time coding make the signal robust, relevant for complex sounds when afferent excitation is saturated [55–57].

#### **5.2. Efferent innervation**

The efferent system of the cochlea provides stimulus protection and fine regulation, in particular noise protection, mediation of selective attention and improvement of signal-tonoise ratio, by innervating the same structures that are responsible for stimulus perception, the inner and outer hair cells. The efferent system also supports adaptation and frequency selectivity by modification of the micromechanical properties of outer hair cells. The efferent system as well as the entire human auditory system is susceptible to strengthening by training and it could be shown that efferent suppression is stronger in musicians [58].

The multipolar lateral efferent neurons originate from the lateral superior olive (LSO) and the multipolar medial efferent system from the periolivary region (medial, ventral and anterior) around the medial superior olivary (MSO) complex and the trapezoid body [59] (**Figure 4**). In human, there is no nucleus trapezoid body and the lateral efferent component is relatively small compared with other species [60–62]. By contrast, the medial superior olivary nucleus reflects a steady increase in primates corresponding to the capability of low-frequency hearing [63].

The well-developed human medial olivary nucleus seems to be the basis for extraction of interaural time and phase differences, whereas the smaller human lateral olivary nucleus probably functions in the analysis of interaural differences in frequency and intensity. The lateral and medial nuclei together form the basis for localization of a sound stimulus and enable us to function in a three-dimensional auditory world [64, 65].

The myelinated medial fibres, which innervate outer hair cells, project ipsi- and contralateral and the unmyelinated lateral fibres, which innervate the dendrites of afferent nerve fibres, project mainly ipsilateral [66]. There exists distinct but complex geometrical and functional alignment of the efferent fibres, their connections and neurotransmitters [67].

Neurotransmission of the efferent system takes place by inhibitory and excitatory transmitters reflecting fine regulation. The numerous neurotransmitters provide for the auditory system a wide operating range to enhance or depress environmental stimuli and can be co-localized as well. The neurotransmitter of the medial olivocochlear fibres includes ACh (acetylcholine), GABA (gamma aminobutyric acid), CGRP (calcitonin gene-related peptide), ATP (adenosine triphosphate), enkephalins and NO (nitric oxide) [68, 69]. The transmitter of the lateral efferent system includes ACh, GABA, CGRP, dopamine, serotonin and opioids such as dynorphin or enkephalin [70–72].

**Figure 4.** Course of the medial and lateral efferent systems. (**A**) The auditory brainstem section. Sound representations from the ear ascend to the olivary complex via the ventral afferent pathway and project back to the ear via dorsal crossed and uncrossed medial and lateral efferent fibres. (**B**) Cross-sectional view of the inner ear. The major ascending afferent pathway arises from inner hair cells. Descending olivocochlear projections terminate on inner and outer hair cells (with permission from Ref. [78], © 1990, Elsevier; and Ref. [79], Copyright © 2004 American Medical Association. All rights reserved).
