Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss.

The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.

Profound bilateral deafness complicating aortic arch surgery.

Hearing loss is a rare complication of cardiac surgery; bilateral profound deafness has never been reported in this setting. A 45-year-old male presented with profound bilateral sudden deafness following arch surgery and frozen elephant trunk. Patient's presentation, surgery details and aetiological mechanisms are discussed.

Neuroprotective Effect of Huperzine A on d-Galactose-Induced Hearing Dysfunction.

BACKGROUND: Administration of d-galactose (d-gal) has been used to create animal models of neurodegenerative diseases, and huperzine A has been used to treat the neurodegenerative diseases such as Alzheimer disease. METHODS: An animal model of hearing dysfunction was established by administration of d-gal in the rats, and the effect of huperzine A on d-gal-induced abnormal hearing function and cochlear damage was investigated. Senescence of the cochlear tissues was examined by ß-galactase staining, and messenger RNA expression of inflammatory cytokines was quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: It was found that d-gal significantly increased auditory brainstem response (ABR) threshold and cellular senescence and decreased neurofilament in the cochlear tissues. Huperzine A could significantly attenuate d-gal-induced increase of ABR threshold and cellular senescence as well as reduction of neurofilament. Moreover, huperzine A could inhibit d-gal-induced activation of nuclear factor kappa-B (NF-κB) in Schwann cells and significantly blocked d-gal-stimulated gene expression of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. CONCLUSION: These findings suggested that d-gal causes hearing dysfunction by inflammatory injury of cochlear neurons and that huperzine A could prevent hearing loss by protecting d-gal-induced physical damage of cochlear tissues.

FGF22 promotes generation of ribbon synapses through downregulating MEF2D.

Cochlear ribbon synapses play a pivotal role in the prompt and precise acoustic signal transmission from inner hair cells (IHCs) to the spiral ganglion neurons, while noise and aging can damage ribbon synapses, resulting in sensorineural hearing loss. Recently, we described reduced fibroblast growth factor 22 (FGF22) and augmented myocyte enhancer factor 2D (MEF2D) in an ototoxicity mouse model with impaired ribbon synapses. Here, we investigated the mechanisms that underlie the FGF22/MEF2D- regulated impairment of ribbon synapses. We generated adeno-associated virus (AAV) carrying FGF22, shFGF22, MEF2D, shMEF2D, calcineurin (CalN), shCalN or corresponding scramble controls for transduction of cultured mouse hair cells. We found that FGF22 was a suppressor for MEF2D, but not vice versa. Moreover, FGF22 likely induced increases in the calcium influx into IHCs to activate CalN, which subsequently inhibited MEF2D. Cochlear infusion of AAV-shFGF22 activated MEF2D, reduced ribbon synapse number and impaired hearing function, which were all abolished by co-infusion of AAV-shMEF2D. Hence, our data suggest that the ribbon synapses may be regulated by FGF22/calcium/CalN/MEF2D signaling, which implied novel therapeutic targets for hearing loss.

Insulin-like growth factor 1 promotes cochlear synapse regeneration after excitotoxic trauma in vitro.

In the context of acquired sensorineural hearing loss (SNHL), cochlear hair cells have long been thought to be among the most vulnerable elements in mammalian cochleae. However, recent studies have indicated that the synaptic connection between inner hair cells (IHC) and spiral ganglion neurons (SGN) can be an important target for the treatment of SNHL. Our previous studies in patients with sudden SNHL demonstrated delayed and gradual hearing recovery following topical application of insulin-like growth factor 1 (IGF-1), suggesting that not only protective but also regenerative mechanisms may account for hearing recovery after treatment with IGF-1. We then hypothesized that IGF-1 has the potential to drive the regeneration of IHC-SGN synapses. To test this hypothesis, we investigated the effects of IGF-1 on IHC-SGN synapses using cochlear explant cultures from postnatal day 2 mice that had been damaged by exposure to the excitatory amino acids N-methyl-d-aspartate and kainate. Cochlear explants that lost IHC-SGN synapses upon exposure to excitatory amino acids were cultured with exogenous IGF-1 for an additional 48 h. We observed increased numbers of IHC-SGN synapses after exogenous IGF-1 application. Pharmacological inhibition of the IGF-1 receptor attenuated the restoration of IHC-SGN synapses by exogenous IGF-1. These findings indicated that IGF-1 induces regeneration of IHC-SGN synapses in cochlear explant cultures from postnatal day 2 mice. Therefore, in a future study we will perform in vivo experiments using adult mice to ascertain the effects of IGF-1 on the regeneration of IHC-SGN synapses.

Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils.

Cochlear implants partially restore hearing via direct electrical stimulation of spiral ganglion neurons (SGNs). However, spread of excitation from each electrode limits spectral coding. We explored the use of optogenetics to deliver spatially restricted and cell-specific excitation in the cochlea of adult Mongolian gerbils. Adeno-associated virus carrying the gene encoding the light-sensitive calcium translocating channelrhodopsin (CatCh) was injected into the cochlea of adult gerbils. SGNs in all cochlea turns showed stable and long-lasting CatCh expression, and electrophysiological recording from single SGNs showed that light stimulation up to few hundred Hertz induced neuronal firing. We characterized the light-induced activity in the auditory pathway by electrophysiological and behavioral analysis. Light- and sound-induced auditory brainstem responses showed similar kinetics and amplitude. In normal hearing adult gerbils, optical cochlear implants elicited stable optical auditory brainstem responses over a period of weeks. In normal hearing animals, light stimulation cued avoidance behavior that could be reproduced by subsequent acoustic stimulation, suggesting similar perception of light and acoustic stimuli. Neurons of the primary auditory cortex of normal hearing adult gerbils responded with changes in firing rates with increasing light intensity. In deaf adult gerbils, light stimulation generated auditory responses and cued avoidance behavior indicating partial restoration of auditory function. Our data show that optogenetic cochlear stimulation achieved good temporal fidelity with low light intensities in an adult rodent model, suggesting that optogenetics might be used to develop cochlear implants with improved restorative capabilities.

Descending projections from the inferior colliculus to medial olivocochlear efferents: Mice with normal hearing, early onset hearing loss, and congenital deafness.

Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC activation could contribute to impaired signal detection in noise.

Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young Rats.

We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs.

Effects of epigallocatechin-3-gallate on proliferation and differentiation of mouse cochlear neural stem cells: Involvement of PI3K/Akt signaling pathway.

Since the majority of hearing impaired patients suffer from the significant loss of sensory hair cells and associated neurons, stem cell-based approaches hold great promise by replacing the damaged tissues in the ears. For instance, stem cells from the spiral ganglion could be isolated and expanded to regenerate neural structures of the inner ear. It is thus necessary to explore the potential procedures that may promote the proliferation and differentiation of such cochlear neural stem cells. In the present study, we study the effects of epigallocatechin-3-gallate (EGCG), a known antioxidant, for potential therapeutic use in NSC regeneration. At a non-toxic concentration, EGCG stimulated both proliferation and neurosphere formation in isolated mouse cochlear neural stem cell (NSC) in vitro. Specifically, the neural differentiation of NSC was promoted by EGCG treatment. The up-regulated neural function by EGCG was also supported by the increased calcium spike frequencies and enhanced neurite complexity in NSC-differentiated neurons. Finally, the induced neuron differentiation and Akt activation of cochlear NSC by EGCG were blocked by PI3 kinase inhibition. These data suggested that EGCG acts through phosphoinositide 3-kinase (PI3K)/Akt signaling in cochlea NSC to promote cell growth and neuron differentiation, which may be exploited for the treatment of hearing loss.

Signal-Coupled Subthreshold Hopf-Type Systems Show a Sharpened Collective Response.

Astounding properties of biological sensors can often be mapped onto a dynamical system below the occurrence of a bifurcation. For mammalian hearing, a Hopf bifurcation description has been shown to work across a whole range of scales, from individual hair bundles to whole regions of the cochlea. We reveal here the origin of this scale invariance, from a general level, applicable to all dynamics in the vicinity of a Hopf bifurcation (embracing, e.g., neuronal Hodgkin-Huxley equations). When subject to natural "signal coupling," ensembles of Hopf systems below the bifurcation threshold exhibit a collective Hopf bifurcation. This collective Hopf bifurcation occurs at parameter values substantially below where the average of the individual systems would bifurcate, with a frequency profile that is sharpened if compared to the individual systems.

Unmyelinated type II afferent neurons report cochlear damage.

In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear.

Synaptic studies inform the functional diversity of cochlear afferents.

Type I and type II cochlear afferents differ markedly in number, morphology and innervation pattern. The predominant type I afferents transmit the elemental features of acoustic information to the central nervous system. Excitation of these large diameter myelinated neurons occurs at a single ribbon synapse of a single inner hair cell. This solitary transmission point depends on efficient vesicular release that can produce large, rapid, suprathreshold excitatory postsynaptic potentials. In contrast, the many fewer, thinner, unmyelinated type II afferents cross the tunnel of Corti, turning basally for hundreds of microns to form contacts with ten or more outer hair cells. Although each type II afferent is postsynaptic to many outer hair cells, transmission from each occurs by the infrequent release of single vesicles, producing receptor potentials of only a few millivolts. Analysis of membrane properties and the site of spike initiation suggest that the type II afferent could be activated only if all its presynaptic outer hair cells were maximally stimulated. Thus, the details of synaptic transfer inform the functional distinctions between type I and type II afferents. High efficiency transmission across the inner hair cell's ribbon synapse supports detailed analyses of the acoustic world. The much sparser transfer from outer hair cells to type II afferents implies that these could respond only to the loudest, sustained sounds, consistent with previous reports from in vivo recordings. However, type II afferents could be excited additionally by ATP released during acoustic stress of cochlear tissues.

Relationship of cochlea with surrounding neurovascular structures and their implication in cochlear implantation.

PURPOSE: The purpose of this investigation was to evaluate the topographic relations of cochlea with vital neurovascular structures and their implications for cochlear implantation (CI). METHODS: Sixty cadaveric human temporal bones were microdissected to expose the basal turn (BT) of cochlea, the carotid canal, the facial canal (FC) and the jugular fossa (JF). The minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were measured. RESULTS: The mean minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were found to be 1.38 ± 0.82, 1.06 ± 0.46 and 4.68 ± 2.21 mm, respectively. The abutment and impingement of carotid canal on anterior cochlear wall was found in three (5 %) and six (10 %) cases, respectively. Thin bone separation was observed between cochlea and FC (0.1 mm) in one case (1.67 %). CONCLUSIONS: The preoperative knowledge of the variant anatomy of BT of cochlea in relation to adjacent vital structures like abutment and impingement of carotid canal and thin bone separation of the BT of cochlea from FC and JF is of immense importance in CI, which may otherwise lead to disastrous consequences during surgery.

Surgical anatomy of facial nerve for revision transmastoid surgery.

We analyze the relationships of the 3 segments of the facial nerve with respect to constant anatomic structures that can be identified during revision surgery via translabyrinthine approach. This study was conducted on 15 formalin-fixed cadavers whose facial nerves were dissected bilaterally under operative microscope via translabyrinthine approach. The distances between the round window niche and the midpoint of the tympanic segment and the beginning of the mastoid segment were 6.64 ± 1.79 mm and 3.99 ± 0.79 mm, respectively. The distances between the tympanic ostium of the eustachian tube and the first and the second genu were 7.02 ± 0.62 mm and 12.25 ± 1.24 mm, respectively. We used the superior semicircular canal, the tympanic ostium of the eustachian tube, and the round window niche as landmarks to identify the facial nerve during revision surgery. Our study also showed that the auricular branch may also be originated from the posterior surface of the facial nerve.

Endoscopic approach to the trigeminal nerve: an anatomic study.

OBJECTIVE: To describe an endoscopic perspective of the surgical anatomy of the trigeminal nerve. METHODS: Nine adult cadaveric heads were dissected endoscopically. RESULTS: Opening the pterygopalatine fossa is important because many key anatomical structures (V2, pterygopalatine ganglion, vidian nerve) can be identified and traced to other areas of the trigeminal nerve. From the pterygopalatine ganglion, the maxillary nerve and vidian nerve can be identified, and they can be traced to the gasserian ganglion and internal carotid artery. An anteromedial maxillectomy increases the angle of approach from the contralateral nares due to an increase in diameter of the piriform aperture, and provides excellent access to the mandibular nerve, the petrous carotid, and the cochlea. CONCLUSIONS: Identification of key anatomical structures in the pterygopalatine fossa can be used to identify other areas of the trigeminal nerve, and an anteromedial maxillectomy is necessary to expose the ipsilateral mandibular nerve and contralateral cranial level of the trigeminal nerve.

Effects of brain-derived neurotrophic factor (BDNF) and electrical stimulation on survival and function of cochlear spiral ganglion neurons in deafened, developing cats.

Both neurotrophic support and neural activity are required for normal postnatal development and survival of cochlear spiral ganglion (SG) neurons. Previous studies in neonatally deafened cats demonstrated that electrical stimulation (ES) from a cochlear implant can promote improved SG survival but does not completely prevent progressive neural degeneration. Neurotrophic agents combined with an implant may further improve neural survival. Short-term studies in rodents have shown that brain-derived neurotrophic factor (BDNF) promotes SG survival after deafness and may be additive to trophic effects of stimulation. Our recent study in neonatally deafened cats provided the first evidence of BDNF neurotrophic effects in the developing auditory system over a prolonged duration Leake et al. (J Comp Neurol 519:1526-1545, 2011). Ten weeks of intracochlear BDNF infusion starting at 4 weeks of age elicited significant improvement in SG survival and larger soma size compared to contralateral. In the present study, the same deafening and BDNF infusion procedures were combined with several months of ES from an implant. After combined BDNF + ES, a highly significant increase in SG numerical density (>50 % improvement re: contralateral) was observed, which was significantly greater than the neurotrophic effect seen with ES-only over comparable durations. Combined BDNF + ES also resulted in a higher density of myelinated radial nerve fibers within the osseous spiral lamina. However, substantial ectopic and disorganized sprouting of these fibers into the scala tympani also occurred, which may be deleterious to implant function. EABR thresholds improved (re: initial thresholds at time of implantation) on the chronically stimulated channels of the implant. Terminal electrophysiological studies recording in the inferior colliculus (IC) revealed that the basic cochleotopic organization was intact in the midbrain in all studied groups. In deafened controls or after ES-only, lower IC thresholds were correlated with more selective activation widths as expected, but no such correlation was seen after BDNF + ES due to much greater variability in both measures.

Dysfunction of the cochlea contributing to hearing loss in acoustic neuromas: an underappreciated entity.

OBJECTIVE: Hearing loss is a common symptom in patients with cochleovestibular schwannoma. Clinical and histologic observations have suggested that the hearing loss may be caused by both retrocochlear and cochlear mechanisms. Our goal was to perform a detailed assessment of cochlear pathology in patients with vestibular schwannoma (VS). STUDY DESIGN: Retrospective analysis of temporal bone histopathology. SETTING: Multi-center study. MATERIAL: Temporal bones from 32 patients with unilateral, sporadic VS within the internal auditory canal. MAIN OUTCOME MEASURES: Sections through the cochleae on the VS side and opposite (control) ear were evaluated for loss of inner and outer hair cells, atrophy of the stria vascularis, loss of cochlear neurons, and presence of endolymphatic hydrops and precipitate within the endolymph or perilymph. Observed pathologies were correlated to nerve of origin, VS volume, and distance of VS from the cochlea. Hearing thresholds also were assessed. RESULTS: VS caused significantly more inner and outer hair cell loss, cochlear neuronal loss, precipitate in endolymph and perilymph, and decreased pure tone average, when compared with the opposite ear. Tumor size, distance from the cochlea, and nerve of origin did not correlate with structural changes in the cochlea or the hearing threshold. CONCLUSION: There is significant degeneration of cochlear structures in ears with VS. Cochlear dysfunction may be an important contributor to the hearing loss caused by VS and can explain certain clinically observed phenomena in patients with VS.

Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea.

AIMS: In our aging society, age-related hearing loss (ARHL) or presbycusis is increasingly important. Here, we study the mechanism of ARHL using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes. RESULTS: We found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e., strial, sensory, and neural degeneration). The molecular mechanisms associated with premature ARHL in SAMP8 mice involve oxidative stress, altered levels of antioxidant enzymes, and decreased activity of Complexes I, II, and IV, which in turn lead to chronic inflammation and triggering of apoptotic cell death pathways. In addition, spiral ganglion neurons (SGNs) also undergo autophagic stress and accumulated lipofuscin. INNOVATION AND CONCLUSION: Our results provide evidence that targeting oxidative stress, chronic inflammation, or apoptotic pathways may have therapeutic potential. Modulation of autophagy may be another strategy. The fact that autophagic stress and protein aggregation occurred specifically in SGNs also offers promising perspectives for the prevention of neural presbycusis.

Anatomy of the human cochlea--implications for cochlear implantation.

Since the classical description by Retzius in 1884, many extensive studies of the micro-anatomy of the human cochlea have been presented. The human cochlea is one of the most difficult tissues to study due to the bony capsule and its delicate contents. Most preparations suffer from post-mortem changes caused by the delay between demise and fixation. For over a decade, we have analyzed human inner-ear tissue obtained at surgery using transmission electron microscopy, scanning electron microscopy, in vitro culture, and immunohistochemistry. These studies show the value of these techniques for fine structural and molecular analyses. Modern cochlear implant surgery requires that ear surgeons are familiar with the intricate anatomy of the human cochlea and its variations. The classical technique to insert electrode arrays through a drilled cochleostomy has been abandoned by some surgeons today. Instead a round-window approach can be used as originally implemented by William House for short electrodes. This so-called 'hook' region of the cochlea presents extensive anatomical variations that can be difficult to foresee on pre-operative computed tomography. CI depends on the functional status of remaining spiral ganglion neurons. These cells are more or less preserved in CI patients but how the conservation influences the outcome of CI is debatable. Notwithstanding their preservation is crucial and more information should be attained about their deterioration and how it can be prevented. Better understanding of structure, function, and regenerative capability is needed to comprehend the nature of electrical stimulation of the peripheral and central nervous system to improve the design of future implant systems.

Efferent modulation of hair cell function.

PURPOSE OF REVIEW: This review covers the articles published between 2010 and early 2011 that presented new findings on inner-ear efferents and their ability to modulate hair cell function. RECENT FINDINGS: Studies published within the review period have increased our understanding of efferent mechanisms on hair cells in the cochlear and vestibular sensory epithelium and provide insights on efferent contributions to the plasticity of bilateral auditory processing. The central nervous system controls the sensitivity of hair cells to physiological stimuli by regulating the gain of hair cell electromechanical amplification and modulating the efficiency of hair cell-eighth nerve transmission. A notable advance in the last year has been animal and human studies that have examined the contribution of the olivocochlear efferents to sound localization, particularly in a noisy environment. SUMMARY: Acoustic activation of olivocochlear fibers provides a clinical test for the integrity of the peripheral auditory system and has provided new understanding about the function and limitations of the cochlear amplifier. Although similar tests may be possible in the efferent vestibular system, they have not yet been developed. The structural and functional similarities of the sensory epithelia in the inner ear offer hope that testing procedures may be developed that will allow reliable testing of the vestibular hair cell function.