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Frequency selectivity of hair cells and nerve fibres in the alligator lizard cochlea.

Receptor potentials of hair cells and spike discharges of cochlear nerve fibres were recorded with micropipettes from the free-standing region of the basilar papilla of anaesthetized alligator lizards in response to tones. In this region the hair-cell stereocilia are free-standing, i.e. they protrude directly into endolymph and are not in contact with a tectorial membrane. The frequency selectivity of hair-cell responses was measured by means of isovoltage contours of the d.c. (V0) and fundamental-a.c. (V1) component of the receptor potential, i.e. iso-V0 and iso-V1 contours. The frequency selectivity of the nerve-fibre discharge was measured by iso-rate (iso-V0) contours. Iso-V0, iso-V1 and iso-V0 contours are basically V-shaped with a characteristic frequency (c.f.) defined as the frequency at which minimum sound pressure (Pmin) is required to evoke the criterion value of the response. Receptor potential iso-V0 contours and neural iso-V0 contours have similar slopes: the mean slopes of the low-frequency sides (dB/decade) are -43.0 and -44.3; the slopes of the high-frequency sides are 85.0 and 80.2. The band widths of iso-V0 and iso-V0 contours away from c.f. are similar (mean values of Q30dB are 0.40 and 0.53, respectively). The band widths of iso-V0 contours near c.f. are narrower than those of iso-V0 contours (mean values of Q10dB are 2.34 and 1.20, respectively). However, the shapes of the contours near c.f. depend on the iso-response criteria, and we have not determined whether or not iso-V0 and iso-V0 contours are similar near c.f. The shapes of iso-V1 contours differ from those of iso-V0 and iso-V0 contours. Nerve fibre c.f.s are tonotopically organized in the nerve, with lowest c.f.s recorded from fibres innervating the border of free-standing and tectorial regions, a region in which hair-cell stereocilia are longest, and the highest c.f.s recorded from fibres innervating the end of the free-standing region in which hair-cell stereocilia are shortest. The c.f. of nerve-fibre response (and by implication hair-cell response) is, therefore, correlated with the height of the stereociliary tuft. The shapes of iso-V0 contours vary systematically with c.f. and, therefore, tonotopically with nerve position.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

N1 latency prolongation in the guinea pig cochlea treated with nitrogen mustard-N-oxide studied by narrow band analysis.

The effect of nitrogen mustard-N-oxide (NMO) upon the click and tone burst-evoked N1 latency was examined in 14 albino guinea pigs. In all animals except one, the pseudothresholds of action potentials were elevated, especially in the high tone area. In addition to the amplitude reduction, the N1 latency was prolonged in 12 animals. The narrow band analysis of N1 revealed that the latency was equally prolonged in all frequency areas, although the amount of the amplitude reduction was much larger in the high frequency area. It was concluded that the prolongation of the N1 latency in NMO-treated animals was due to dysfunction of outer hair cells along the entire cochlear partition.

Acoustic Stimulation↗

Role of perilymphatic fistula in sudden hearing loss: an animal model.

The electrophysiologic response of the guinea pig cochlea was monitored after sequential lesions to Reissner's membrane and the round window (RW). Action potential (AP) responses to click stimuli were recorded from the RW before and after discrete puncture-type lesions were created in the cochlear partition of the second turn. Observed decrements were typically minor, comparable to no greater than 10 dB attenuation of stimulus intensity. The RW membranes then were perforated to create perilymphatic fistulas. Further monitoring demonstrated a rapid (within 5 to 10 minutes), severe decrement in AP amplitude and latency, with complete loss of the AP within 1 hour. Control animals with RW perforations alone did not show these decrements. Correct placement of the second turn lesions was documented by histology. We conclude that discrete lesions in the cochlear duct are not reflected in the AP input-output functions unless there is a fluid leak from the RW, and thus present a possible model for idiopathic sudden hearing loss.

Action Potentials↗

Effects of kanamycin sulfate on cochlear potentials and potassium ion permeability through the cochlear partitions.

The cochlear microphonics (CM), endocochlear potential (EP) and potassium ion activities in the endolymph and perilymph were measured in guinea pigs which received daily successive intramuscular injections of 500 mg/kg of body weight of kanamycin sulfate. Preyer's reflex threshold at 8 kHz began to increase after the 5th day of kanamycin treatment and disappeared on the 11th day. The maximum output of CM at 8 kHz began to decrease with a time course similar to Preyer's reflex. The potassium ion activities in the endolymph and perilymph and the EP did not change appreciably through all experimental days. The magnitude of the negative EP decreased in parallel with the reduction in CM and the relative potassium conductance (GK) between the endolymph and perilymph. These results lend support to the hypothesis that the site of production of the negative EP is probably in the hair cells and that the negative EP is mainly dependent on the permeability of the potassium ions in the organ of Corti.

Animals↗

Otoacoustic emissions without somatic motility: can stereocilia mechanics drive the mammalian cochlea?

Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less vulnerable to cochlear insult, and their dependence on the OHC function is more controversial. Here, the mechanism underlying high-level DPOAE generation is addressed using a mutant mouse line lacking prestin, the molecular motor driving OHC somatic motility, required for cochlear amplification. With prestin deletion, attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were shifted by approximately 50 dB, matching the loss of cochlear amplifier gain measured in compound action potentials. In contrast, at high sound levels, distortion products in the cochlear microphonic (CM) of mutants were not decreased re wildtypes (expressed re CM at the primaries). Distortion products in both CM and otoacoustic emissions disappeared rapidly after death. The results show that OHC somatic motility is not necessary for the production of DPOAEs at high SPLs. They also suggest that the small, physiologically vulnerable DPOAE that remains without prestin-based motility is due directly to the mechanical nonlinearity associated with stereociliary transduction, and that this stereocilia mechanical nonlinearity is robustly coupled to the motion of the cochlear partition to the extent that it can drive the middle ear.

Acoustic Stimulation↗

Experimental basis for lidocaine therapy in cochlear disorders.

In order to further our basic understanding of the effects of lidocaine hydrochloride in the inner ear, cochlear potentials and blood flow (CBF) were assessed after intravenous (i.v.), anterior inferior cerebellar artery (AICA), and local round window (RW) lidocaine administrations in guinea pigs and rats. Lidocaine RW applications produced a dose dependent decrease in compound action potentials (CAP) and cochlear microphonics (CM). The sensitivity changes were more pronounced at high frequencies. These findings suggest that lidocaine has specific pharmacological action in the inner ear other than simple anesthesia of the auditory nerve. The basal turn endocochlear potentials (EP) were not altered by topical lidocaine, implicating altered organ of Corti function following local application of lidocaine. RW applications of lidocaine had no effect on CBF or systemic blood pressure (BP). I.v. infusions caused substantial reductions in BP. In the case of systemic infusions the percent changes in CBF were equal to and accountable by the BP changes. The microinfusions (50 mg/ml, 100 nl/min) through AICA produced a 30%, long lasting increase in CBF. However, neither systemic lidocaine nor AICA infusions had an effect on CAP or CM. These findings indicate that systemically given lidocaine may not cross the blood-cochlear barrier and that the cochlear electrophysiological effects due to lidocaine when given locally are partly mediated by direct influence on cochlear hair cell function; they also suggest that lidocaine-induced interference with active ion transport in the lateral wall or an influence on CBF are not contributing factors.

Action Potentials↗

Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy.

OBJECTIVE: To describe the effects of long-term mild hypoxia and of glutamate poisoning on the functional properties of the cochlea. METHODS: Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). RESULTS: In contrast to the effects of acute anoxia, in which all aspects of cochlear function are simultaneously lost, mild, long-term hypoxia results in a clear differential effect on outer versus inner hair cell systems. During a 2-hour period of mild hypoxia, ABR amplitude and threshold deteriorate significantly, whereas outer hair cell function, as reflected by otoacoustic emissions, shows little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of glutamate (1-10 mM), where the cochlear microphonic and the otoacoustic emissions are unchanged, whereas cochlear action potential amplitudes are reduced. CONCLUSION: These studies demonstrate a difference in vulnerability of inner and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy.

Animals↗

Basilar membrane mechanics at the base of the chinchilla cochlea. II. Responses to low-frequency tones and relationship to microphonics and spike initiation in the VIII nerve.

Low-frequency stimuli (40- to 1000-Hz tones) have been used to correlate the motion of the 8-to 9-kHz place of the chinchilla basilar membrane with the cochlear microphonics recorded at the round window and with the responses of auditory nerve fibers with appropriate characteristic frequency. At the lowest stimulus frequencies, maximum displacement of the basilar membrane toward scala tympani occurs in near synchrony with maximum rarefaction at the eardrum and maximum negativity at the round window; at higher frequencies, the mechanical and microphonic response phases progressively lag rarefaction, reaching - 240 deg at 1000 Hz. At most frequencies (40-1000 Hz) near-threshold neural responses, once corrected for neural travel-time and synaptic delays, somewhat lead (by some 40 deg) maximal scala tympani displacement and maximal negativity of the round window microphonics. The variation of sensitivity with frequency is similar for basilar membrane displacement and microphonic responses: Under open-bulla conditions, sensitivity is constant for frequencies between 100 and 1000 Hz; below 100 Hz, sensitivity decreases at rates close to 12 dB/oct toward lower frequencies. Neural response sensitivity matches BM displacement more closely than BM velocity.

Action Potentials↗

Autoradiographic measurement of regional brainstem blood flow: occlusion of the anterior inferior cerebellar artery.

Autoradiography was used to measure regional brainstem blood flow in Wistar rats following permanent left anterior inferior cerebellar artery (AICA) occlusion. With the AICA occluded, blood flow to the left vestibular nucleus decreased 31% while flow to the left cochlear nucleus decreased 47% when compared to the right (unobstructed) side. In the rat, the median pontine branch of the basilar artery was found to provide the principal blood supply to the vestibular nucleus. Electrocochleography was also used to measure the action potential (AP), summating potential (SP) and cochlear microphonics (CM) during left AICA occlusion. The AP disappeared completely after at least 7 min, while the SP polarity changed from negative to positive. Findings also showed that CM2 did not disappear completely in pre-mortem animals.

Action Potentials↗

[Effects of lowering perilymph calcium concentration on various cochlear potentials].

In the present experiment, changes in compound action potentials of auditory nerve (CAP), cochlear microphonics (CM) and endocochlear potentials were observed when the calcium concentration of perilymph was reduced by means of perilymph perfusion, with the aim of analyzing how calcium was involved. Perfusion with Ca(2+)-free artificial perilymph reversibly suppressed both CAP and CM amplitudes, but did not alter the basic nonlinear properties of CAP I/O curve. Furthermore, the perfusion did not alter the EP and negative EP (n-EP) induced by anoxia but eliminated the fast change of EP with respect to turning on and off of intense sound. The mechanisms underlying the effects of calcium are discussed.

Action Potentials↗

The effect of adenylate cyclase stimulation on endocochlear potential in the guinea pig.

Forskolin, a diterpene extracted from Coleus forskohlii, is potentially an important tool for studying the modulation of ionic currents by cAMP because it stimulates adenylate cyclase in a variety of cells. We studied the effect of forskolin on cochlear potentials and found that its perfusion of the scala vestibuli (SV) to a concentration more than 10(-5) M and the scala tympani (ST) to more than 10(-4) M produced a reversible elevation of the endocochlear potential (EP) in a dose-dependent manner. The cochlear microphonics recorded simultaneously with the EP was not depressed during the EP elevation. A large negative EP was induced by anoxia following the SV perfusion with forskolin (2 X 10(-4) M). The results suggest that the EP elevation produced by forskolin does not result from the decrease in the negative component of EP but from the increase in the positive component of EP.

Adenylyl Cyclases↗

The Davis theory: a review, and implications of recent electrophysiological evidence.

The Davis theory of mechano-electrical transduction asserts that the endocochlear potential and the hair cell resting potential summate to provide a driving force for current flow through the hair cell. However, while a variety of agents which depress the endocochlear potential simultaneously depress auditory nerve sensitivity and reduce the cochlear microphonic, recent reports suggest that the hair cells may be depolarised without such effects ensuing. The relevant literature is reviewed.

Animals↗

Development of morphological and physiological changes in the cochlea induced by cytomegalovirus.

The effect of viral infection in the cochlea was investigated by inoculation of live cytomegalovirus or inactivated virus. Auditory thresholds were measured on the day of inoculation and on the terminal day. Two to 8 days following inoculation, the animals were killed and the cochleas were evaluated histologically. The compound nerve potential showed an increase in threshold prior to the cochlear microphonic, indicating the nerve was affected prior to the outer hair cells. All experimental cochleas contained inflammatory and cytomegalic inclusion cells and showed degenerative changes. The number of infected cells was small relative to the histopathology. Control cochleas had normal structure and function. The degeneration, therefore, might be mediated by inflammation as well as by the cytopathic effect of the virus. Viral infections, therefore, might be better managed with anti-inflammatory therapy in addition to antiviral agents.

Animals↗

Micromechanical effects in the cochlea of tetracaine.

Local anesthetics applied in the tympanic cavity have earlier been shown to affect the gross receptor potentials in reducing the cochlear microphonics and increasing the positive summating potential. To study the effects of this drug on the mechanical responses in the cochlea, vibrations were measured using laser heterodyne interferometry in an isolated in vitro temporal bone preparation from the guinea pig. Measurements were made at a set of frequencies in the fourth cochlear turn from the Hensen's cells and the outer hair cells in response to sound applied to the ear. The tuning curves of the fundamental and the second harmonic components of the vibratory responses were plotted. When 2 mM tetracaine was applied, the high frequency slope of the second harmonic curve shifted down in frequency, this caused the frequency of the maximum of second harmonic tuning to shift down. These changes were reversible when tetracaine was washed out. Observations were also made in the temporal bone preparation in vitro with a confocal microscope. Fluorescent probes were used to label various structures in the organ of Corti. Optical sections were obtained by tilting the organ permitting a view from the side like a radial section through the organ. Images were acquired before, during and after application of tetracaine and were later analyzed with a computer program. Simultaneously, cochlear microphonics and the summating potential were obtained to monitor the electrical response of the preparation. Although the cochlear microphonics and summating potential decreased when 2 mM tetracaine was applied, structural changes were not measurable in the organ of Corti. The decrease was reversible when tetracaine was washed out. It is concluded that tetracaine affected the high frequency part of the non-linear second harmonic component, possibly by lowering the stiffness of the stereocilia bundle or the body of the outer hair cells.

Acoustic Stimulation↗