Olivocochlear Efferent Fibers Research Articles

High calcium permeability and calcium block of the α9 nicotinic acetylcholine receptor

At the synapse between olivocochlear efferent fibers and outer hair cells (OHCs) of the cochlea, a non-classical ionotropic cholinergic receptor allows Ca 2+ entry into the hair cell, thus activating a Ca 2+-sensitive K + current which hyperpolarizes the cell’s membrane. In the mammalian ear, this leads to a reduction in basilar membrane motion, altering auditory nerve fiber activity and reducing the dynamic range of hearing. The α9 nicotinic acetylcholine receptor (nAChR) subunit mediates synaptic transmission between cholinergic olivocochlear fibers and OHCs. Given that Ca 2+ is a key player at this inhibitory synapse, we evaluated the permeability to Ca 2+ of the recombinant α9 receptor expressed in Xenopus laevis oocytes and the modulation of its activity by extracellular Ca 2+. Our results show that the α9 receptor is highly permeable to Ca 2+ and that this cation potently blocks monovalent currents through this channel (IC 50=100 μM, at −70 mV) in a voltage-dependent manner. At a Ca 2+ concentration similar to that found in the perilymph bathing the base of the OHCs, approximately 90% of the Na + current through the α9 receptor is blocked, suggesting that one of the main functions of this channel could be to provide a pathway for Ca 2+ influx.

Innervation of supporting cells in the apical turns of the guinea pig cochlea is from type II afferent fibers.

The outer supporting cells in the apical turns of the guinea pig cochlea receive a dense innervation. Our previous study (Fechner et al. [1998] J. Comp. Neurol. 400:299-300) suggested that this innervation of the Deiters' and Hensen's supporting cells was not derived from efferent fibers of the olivocochlear bundle, but its origin has not been further specified. To test the hypothesis that the innervation was afferent in origin, we traced apical afferent fibers that were retrogradely labeled by extracellular injections of horseradish peroxidase. Labeled afferent fibers were of two types: type I fibers contacted inner hair cells, whereas type II fibers crossed the tunnel and contacted outer hair cells. Significantly, most of the type II fibers also formed branches to the outer supporting cells. Although a few olivocochlear efferent fibers formed such branches, counts indicated that the overwhelming majority of the branches were produced by type II afferent fibers. These branches were not produced by basal type II fibers. Apical type II fibers also differed from basal fibers by having shorter lengths, spiraling both apically and basally, and contacting all three rows of outer hair cells. These innervation differences suggest differences in the ways that information from outer hair cells is processed in the apex versus the base of the cochlea.

Characterization of voltage dependent calcium channels on the lateral olivocochlear efferent fibers of the guinea pig

Using in vitro superfusion technique the release of [ 3H]-dopamine from the lateral olivocochlear efferent fibers of the cochlea was investigated. Our previous study gave the first neurochemical evidence for the transmitter role of dopamine and proved its neuronal origin. Using specific antagonists now we characterized the voltage-dependent calcium channels (VDCCs) involved in the release of dopamine evoked by electrical stimulation of the cochlear tissue. Verapamil or nifedipine, and Ni 2+ failed to affect the release, indicating that neither L-, nor T-type VDCCs are essential for the release process. The fact that ω-conotoxin inhibited the release of dopamine from lateral olivocochlear efferent fibers suggests, that N-type VDCCs are required for the calcium influx during electrical stimulation. These VDCCs could be presynaptic targets of modulation of the dopamine release under pathological conditions or in therapy.

Suppression of otoacoustic emission is unchanged after several minutes of contralateral acoustic stimulation

The influence of variable durations of contralateral acoustic stimulation on the suppression of click-evoked otoacoustic emissions was investigated in order to determine whether olivocochlear efferent fibers are equally effective whatever the acoustical stimulation duration or if they show fatigue. The suppression effect was measured for contralateral stimulus durations ranging from 10 to 180 s prior to the onset of otoacoustic emission recording, and continuing throughout the recording time (60 s). No significant stimulus duration effect was found.

Evidence of a medial olivocochlear involvement in contralateral suppression of otoacoustic emissions in humans

Otoacoustic emissions (OAEs) evoked by click stimuli were recorded in both ears of 20 normal human subjects, in the presence and absence of a contralateral masking broad band noise. No difference in the amplitude of OAE suppression was noted between the first tested ear and the second one. In addition, 20 pathological subjects were tested according to the same protocol. Ten of them belonged to a group of patients whose vestibular nerve was sectioned on one side to relieve incapacitating vertigo and thus represented a group in whom olivocochlear efferents were severed. A great reduction of suppression observed in the operated ear suggested that olivocochlear efferent fibers are necessary to obtain a full suppressive effect. Three of the pathological subjects were patients who had undergone a decompression of the facial nerve which necessitated the same surgical approach as vestibular neurotomy, but without any section of vestibular fibers. This surgical control group demonstrated that the surgical act by itself cannot explain the difference observed in the neurotomized group. Finally, seven of the pathological subjects were patients with Bell's palsy, which paralyses the facial nerve and abolishes the stapedial reflex. No suppression difference was observed between healthy ears and ears without stapedial reflex. Therefore, it appeared that the stapedial reflex was not involved in the contralateral suppression of EOAEs. However, as the tensor tympani muscle remained functional in these patients, its involvement in the suppressive effect cannot be excluded.

Effects of noise stimulation on cochlear dopamine metabolism

Dopamine (DA) appears to be one of the putative neurotransmitters of the lateral efferent olivocochlear fibers. However, its role in the cochlear physiology remains unknown. In this study, animals were exposed for 1 h to white noise at 70, 90 or 110 dB SPL or were kept in silence conditions. Afterwards, the cochlear content of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were analyzed using HPLC coupled to electrochemical detection. Cochlear DA concentration decreased with the noise intensity, while cochlear DOPAC and HVA concentrations increased. Males presented higher cochlear DOPAC contents and lower HVA contents than females. This sexual dimorphism could be related to the link between DA and gonadal steroids. Present results show that DA, as other lateral efferent neurotransmitters, is released and metabolized in relationship with the noise stimulation, and suggest that DA could be involved in the modulation of the type I afferent fiber activity.

Expression of GAP-43 in growing efferent fibers during cochlear development.

The development of olivocochlear efferent fibers has been studied by means of the immunocytochemical detection of the growth-associated protein GAP-43. This study has been carried out in pre- and postnatal, developing, pigmented rats. Results indicate that olivocochlear efferents reach the developing auditory epithelium from embryonic day 18 on. GAP-43-like immunoreactivity persists in the organ of Corti until the beginning of the second postnatal month. The relationships between the expression of GAP-43 in olivocochlear efferent fibers and other plasticity-related phenomena are discussed.

Piribedil could modify dopamine turnover in cochleas under noise stimulation.

Dopamine (DA) is one of the putative neurotransmitters of the lateral efferent olivocochlear fibers. The cochlear DA content after noise exposure was analyzed using high-performance liquid chromatography coupled with electrochemical detection. Animals were exposed for 1 h to white noise at 70, 90 or 110 dB SPL or were kept in conditions of silence. Half of the animals were pretreated with piribedil, a D2 agonist, and the other half served as controls. In control (untreated) animals, noise stimulation resulted in a progressive decrease of cochlear DA concentration. This decrease was scarcely detected when animals were pretreated with piribedil. Present findings indicate that piribedil modifies cochlear DA turnover under noise stimulation.

Intracochlear application of acetylcholine alters sound-induced mechanical events within the cochlear partition

Activation of olivocochlear (OC) efferent fibers has been suggested to alter micromechanical events occurring within the cochlear partition, possibly through an effect of the efferent neurotransmitter (acetylcholine; ACh) on outer hair cells (OHCs). Based on the widely-accepted assumption that otoacoustic emissions reflect OHC activity, we investigated the in vivo influence of ACh on OHCs by studying alterations in emission amplitude with local ACh application. Distortion product otoacoustic emissions (DPOAEs) were measured in anesthetized guinea pigs before, during, and after intracochlear application of ACh (250 μM) with the cholinesterase inhibitor, eserine (20 μM). Perfusion of ACh/eserine was associated with a desensitizing reduction in DPOAE amplitude of approximately 4.4 dB. This reduction was intensity-dependent, with greater and more consistent reductions observed for DPOAEs elicited by low- than by moderate-intensity primaries. The response reduction was not seen during consecutive ACh perfusions performed without an intervening artificial perilymph wash, and was effectively blocked in the presence of pharmacologic antagonists of OC efferent activity (curare, 50 μM, strychnine, 50 μM). Finally, a similar alteration in DPOAE amplitude was never seen during perfusion of the control (artificial perilymph) solution alone. It is argued that these results support the hypothesis that OC efferent activation can alter sound-induced cochlear mechanical events.

Immunoelectron microscopic localization of neurotransmitters in the cochlea

This paper presents the works and methods of our respective laboratories using electron microscopic immunocytochemistry to identify and localize cochlear neurotransmitters. Antibodies to various prospective neurotransmitters and associated enzymes have been used to study the ultrastructural localization of several candidates for olivocochlear efferent neurotransmitters previously suggested by light microscopic immunocytochemistry. Antibodies against enkephalins label lateral olivocochlear efferent fibers. Antibodies against choline acetyltransferase (ChAT) (an enzyme marker for acetylcholine) label a major population of both lateral and medial efferent fibers and terminals, whereas antibodies to gamma-aminobutyric acid (GABA) label what might be a small subpopulation of both the lateral and medial efferent systems. The GABA-like immunostained medial efferent fibers are preferentially located in the upper turns of the guinea pig cochlea, particularly the third turn. Immunoelectron microscopy shows that neither GABA nor ChAT immunolabels all medial efferent terminals, regardless of cochlear turn. All the different types of immunolabeled efferent terminals have been observed to make characteristic synaptic contacts; lateral efferent terminals on afferent dendrites and medial efferent terminals on outer hair cells and occasionally on type II afferent dendrites. Other types of contacts involving GABA-like, and sometimes met-enkephalin-like, immunostained fibers are occasionally seen particularly in the upper turns of the cochlea. Immunoelectron microscopic results suggest that both medial and lateral efferent systems might be further subdivided on the basis of differences in neurotransmitters. Future trends of immunocytochemical research on cochlear neurotransmitters are proposed, particularly colocalization studies, which show a complex pattern of coexistence of neurotransmitters in the lateral efferent system.

Immunocytochemical detection of glutamate decarboxylase in the postnatal developing rat organ of corti

Using a fluorescent avidin-biotin technique, we have immunolocalized the GABA synthesizing enzyme, glutamate decarboxylase, in postnatal developing and adult rat organs of Corti. At birth, the glutamate decarboxylase-like immunoreactivity is already present in the basal turn below the inner hair cells, i.e. within lateral olivocochlear efferent fibers of the inner spiral bundle. In the apical turn, the inner spiral bundle displays an immunoreactivity as early as postnatal day 3. Only the outer hair cells of the upper second turn and apex receive fibers immunostained for glutamate decarboxylase that most probably belong to the medial olivocochlear efferent innervation. They first appear at this level at postnatal day 15. Within these two regions of the organ of Corti, the glutamate decarboxylase-like immunoreactivity reaches an adult-like pattern at postnatal days 17–18. These results strengthen the hypothesis that GABA is a putative neurotransmitter that could be used by subpopulations of the two olivocochlear innervations. They also suggest that GABA either plays a neurotrophic function or participates in the regulation of the first cochlear potentials at the level of lateral efferent synapses.

Physiology of cochlear efferent and afferent neurons: Direct comparisons in the same animal

Exposure of the vestibulo-cochlear anastomosis in the cat allows single-unit recording of afferent fibers originating from inner hair cells and olivocochlear efferent fibers to the outer hair cells. Comparison of data obtained from individual animals show similarities in absolute threshold and dynamic range between the efferent fibers and that subset of auditory-nerve afferents with low spontaneous rates and high thresholds [Liberman (1978) J. Acoust. Soc. Am. 63, 442–455]. The afferent-efferent comparisons also show that interanimal variability in efferent excitability (thresholds and maximum discharge rates) is directly correlated with variation in the mean spontaneous discharge rate of the afferent fiber population. It is suggested that interanimal differences in efferent excitability may explain some of the interanimal variability in susceptibility to acoustic trauma.