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M A Cheatham

Publications and source records attributed to M A Cheatham.

At least 19 recordsLinked to original sources

Two-tone suppression in inner hair cell responses: correlates of rate suppression in the auditory nerve.

Inner hair cell (IHC) recordings were made from second turn of the guinea pig cochlea where characteristic frequencies are approximately 4000 Hz. In order to compare IHC responses with rate suppression measured in the auditory nerve, suppressors were introduced that produced little or no response in the hair cell. The effects of a variable-frequency suppressor on a constant-frequency probe, placed near characteristic frequency, were also investigated since this paradigm is commonly used in single unit experiments. Resulting magnitude changes were measured in the fundamental component of the ac receptor potential and/or in the total dc produced in the region of temporal overlap between the two stimulus inputs. This latter component is especially important when considering how changes in IHC responses relate to decreases in discharge rate in single auditory nerve fibers. Since the ac receptor potential is filtered by the hair cell's basolateral membrane, the dc component probably controls transmitter release at the characteristic frequency of these second-turn IHCs. Based on results from these and previous experiments, a proposal is advanced to explain the evolution of two-tone suppression in the peripheral auditory system. The paper also discusses the use of excitatory versus non-excitatory suppressors and includes a description of two-tone suppression areas at the mechanical, IHC and single unit levels. The explanation of low-side suppression areas is of special interest since hitherto they have been difficult to model (Kim, 1985).

Acoustic Stimulation

Physiological correlates of off-frequency listening.

Recordings are made from inner hair cells (IHC) in the second turn of the guinea pig cochlea where characteristic frequencies (CF) are approximately 4000 Hz. Results from experiments using two stimulus inputs suggest that the characterization of two-tone suppression at this more-basal recording location is similar to the reported for IHCs in the third turn (Cheatham and Dallos, 1989, 1990a, 1990b). For example, introduction of a suppressor causes IHC frequency response functions to become narrower with the smallest magnitude reductions occurring between 1/2 to 1 octave below CF. In this frequency region, where suppression is minimal, it was also observed that suppressor magnitude was reduced by the probe. In other words, the mutual suppression of probe and suppressor may contribute to the sharpening of these functions. Since the peak of the frequency response function shifts to a lower frequency in the presence of the suppressor, these results may provide a physiological correlate of the psychophysical phenomenon known as 'off-frequency listening.'

Acoustic Stimulation

Comparison of low- and high-side two-tone suppression in inner hair cell and organ of Corti responses.

Two-tone interactions were measured from inner hair cells and from the organ of Corti fluid space in the third turn of the guinea pig cochlea. At relatively low stimulus levels, a low-side suppressor caused frequency response functions to become broader. Phase changes exhibited a lag/lead transition around the characteristic frequency in harmony with the change in magnitude. These patterns are similar to those previously documented for a high-side suppressor (Cheatham and Dallos 1989) and suggest that suppression is not simply an attenuation phenomenon since level reductions for single-tone inputs produce response patterns which are mirror images of those obtained for the two-tone conditions. In contrast to the low-level results, data measured at moderately high stimulus levels indicate that the magnitude changes produced by both low- and high-side suppressors are qualitatively similar to changes generated by reducing the input sound level. In other words, ac frequency response functions become narrower, partially reversing the broadening of these functions which occurs as sound level increases. Companion phase measures, however, demonstrate that low- and high-side suppressors, in spite of producing similar changes in filter shape, do not produce similar changes in response phase. In fact, neither of the two-tone conditions produce response patterns similar to the one associated with reducing the input sound level.

Acoustic Stimulation

Two-tone interactions in inner hair cell receptor potentials: AC versus DC effects.

Two-tone suppression was studied in both ac and dc receptor potentials recorded from inner hair cells in the third turn of the guinea pig cochlea. Frequency response functions for the ac component obtained at moderate intensities indicate that frequency selectivity is enhanced when a high-side suppressor is added to the stimulus. This occurs because the largest reductions in magnitude take place well above and below the characteristic frequency (CF) of the cell. Changes near CF are relatively small. In contrast, frequency response functions for the dc receptor potential become broader in the presence of an excitatory suppressor. The significance of these findings for the processing of complex stimuli is considered.

Acoustic Stimulation

Effects of electrical polarization on inner hair cell receptor potentials.

Ac and dc receptor potential components in response to tone-burst stimuli were measured from inner hair cells in the third cochlear turn of the guinea pig. Comparisons were sought between conditions when constant polarizing current was injected into the cell through the recording electrode and when there was no extrinsic current. Hyperpolarization of the cell increased all responses, while depolarization decreased them. The input-output functions were vertically translated by current injection. The extent of translation was a function of current level. In addition, the amount of current-induced change was frequency dependent. Largest changes were seen at low frequencies and the current-induced change tended toward a constant high-frequency asymptote between 1-2 kHz. Changes in the dc response component were considerably in excess of those for the fundamental ac response. The frequency-dependent effects are quantified with the aid of a hair cell circuit model [P. Dallos, Hear. Res. 14, 281-291 (1984)]. It is assumed that the quantity altered by polarizing current (actually by the transmembrane voltage) is the resistance of the cell's basolateral membrane.

Animals

Two-tone suppression in inner hair cell responses.

In an attempt to characterize certain aspects of two-tone suppression (2TS), ac receptor potentials were recorded from mammalian inner hair cells (IHC) in the third turn of the guinea pig cochlea. By comparing magnitude and phase changes occurring during suppression with predictions made on the basis of level-dependent responses to single-tone inputs, it is possible to determine whether 2TS is mimicked by simply attenuating stimulus intensity. Results indicate that the effects of suppression are not simulated by simple input attenuation for low probe levels which produce responses below saturation. In these situations, the suppressor causes a decrease in the magnitude of the ac receptor potential with the largest deviations measured at the characteristic frequency (CF) of the cell. Thus, frequency response functions become broader. Response phase goes through a lag/lead transition at CF, also opposite to the results expected by simply decreasing input to the cell. At higher probe levels, within the saturation region, the magnitude reductions produced during 2TS are largest for stimulus frequencies well below and well above CF. This effect partially reverses the broadening of frequency response functions seen at moderate intensities with possible benefits for the processing of complex stimuli at conversational levels. Although the magnitude data obtained at high probe levels are consistent with the attenuation hypothesis, the companion phase measures did not show the expected lead/lag transition through CF since phase changes were generally lags. Consequently, the high-level suppression data suggest that 2TS may reduce input to the IHC but in a way which is not equivalent to the attenuation of a single-input stimulus.

Acoustic Stimulation

Nonlinearities in cochlear receptor potentials and their origins.

Using intracellular recording methods in vivo [P. Dallos, J. Neurosci. 5, 1591-1608 (1985)], various nonlinear characteristics of receptor potentials from hair cells located in the low-frequency region of the guinea pig cochlea have been examined. Patterns of saturation for ac and dc response components obtained from Fourier analysis and directly from averaged waveforms are studied. Growth patterns of lower harmonic components are investigated and the interesting nonmonotonic properties of even harmonics noted. The latter are seen in both inner and outer hair cell responses, primarily with stimuli near the cells' best frequency. Fundamental ac and the dc potentials occasionally exhibit nonmonotonic growth. These patterns are studied and their occurrence in inner and outer hair cell responses considered.

Acoustic Stimulation

Positive endocochlear potential: mechanism of production by marginal cells of stria vascularis.

The positive endocochlear potential (EP+) and high K+ concentration of the endolymph in the scala media of the mammalian cochlea are unusual. They have long been assumed to be due to a putative K-pump in the luminal membrane of the marginal cells of the stria vascularis, which were believed to have a negative internal potential. We show that the cell potential is more positive than the EP+, and that the ion pump is conventional Na,K-ATPase, probably in the basolateral membrane. The latter was determined from experiments in which the ionic environment of the strial cells was controlled by perfusion of the perilymphatic space of the cochlea, in the absence of vascular circulation. While the usual EP+ was maintained by normal perfusate, replacement of Na+ by choline resulted in a negative EP, showing that Na,K-ATPase is necessary for the production of EP+. Elimination of K+ as well as Na+ from the perfusate did not change the value of the negative EP, showing that no K-ATPase is involved.

Animals

Growth of suppression in the cochlear potentials.

Measurement of two-tone effects in the cochlear microphonic and summating potential indicates that the growth of suppression is different for these two cochlear potentials. Whereas the CM response to the fundamental is reduced 10 dB for each 10 dB increase in suppressor level, the SP decreases at a faster rate; approximately 20 dB per 10 dB increase. Slopes of functions for the CM response to the second harmonic are similar to those for the dc component. Since these results are consistent with the notion that suppression operates by attenuating the input to the CM generator, they are consonant with a mechanical origin of suppression.

Animals

Summating potential (SP) tuning curves.

Two methods were used to extract frequency specific information from the gross d.c. cochlear potential, the summating potential (SP). The first approach was to derive SP tuning curves using a two-tone simultaneous masking procedure; the second to obtain SP iso-response functions. The influence of various parameter changes on the configuration of these functions was also investigated. While SP tuning curves measured using the two-tone paradigm have higher Q10 dB values than SP iso-response functions in the base of the cochlea, the latter have the advantage of avoiding contamination by various nonlinear phenomena which are inherent in the simultaneous tone-on-tone masking procedure. Since SP tuning curves are similar to those for basilar membrane motion (Sellick, P.M., Patuzzi, R. and Johnstone, B.M. (1982): J. Acoust. Soc. Am. 72, 131-141) and the whole nerve action potential (AP) (Cheatham, M.A. and Dallos, P. (1979): J. Acoust. Soc. Am. 65, S13), nearly the same degree of tuning may be reflected at these peripheral recording locations.

Action Potentials

Muscarinic acetylcholine receptor binding in the guinea pig cochlea.

Because of the possibility that olivocochlear bundles may use acetylcholine as an inhibitory transmitter, we examined the cochlea of the guinea pig for cholinergic receptor binding sites. Binding of the potent muscarinic antagonist [3H]quinuclidinyl benzilate (3H-QNB) showed that the cochlea has sites with the pharmacological specificity of muscarinic cholinergic receptors. Specific 3H-QNB binding was saturated at 0.8 nM and was half-saturated at 0.03 nM concentrations. Total 3H-QNB binding was reduced 70% in the presence of saturating doses of acetylcholine, oxotremorine and atropine, and half-maximal competition occurred at doses comparable to those at other muscarinic sites in the central and peripheral nervous systems. The nicotinic specific antagonist d-tubocurarine did not block 3H-QNB binding at concentrations known to be effective in electrophysiological experiments, indicating the sites measured here were not the mixed muscarinic-nicotinic receptor type postulated for some systems. Localization of binding sites, as done by hand microdissection methods, showed that basal cochlear turns had five times the number of sites as apical turns. Most of the sites were evenly divided between the bony modiolus and the auditory nerve, although some sites were measured in sensory tissue. These results support the idea that cholinergic communication occurs in the cochlea, but they are also consistent with the hypothesis that other receptor mechanisms may be involved in olivocochlear inhibition.

Acetylcholine

Two-tone interactions in the cochlear microphonic.

Two-tone interactions are explored for the cochlear microphonic (CM) in the guinea pig. Recordings are made from turns one and three using differential electrodes in the perilymphatic space or pipettes placed in scala media through a fenestra over the stria vascularis. We focus on magnitude changes associated with the introduction of appropriate interference tones and on various types of phase shift concomitant with these magnitude variations that have not received documentation in the literature. Based on extensive parametric data, it is suggested that some features of the gross interference phenomenon may be a consequence of the vectorial summation of outputs from contributing hair cell generators. These spatial effects appear to determine phase behavior and the influence of probe frequency on the frequency of maximal interference. In addition, the apparent interval between out defined best frequency (CF) and the frequency of maximal interference is most likely due to an underestimation of CF resulting from phase cancellation between CM-producing hair cell populations. However, after compensating for these spatial effects, several aspects of the CM interference phenomenon seem to be analogous to two-tone suppression in auditory nerve fibers. A direct one-to-one relationship is not implied since the latter reflect the outputs of inner hair cells while CM interference most likely reflects outer hair cell behavior. As a result, the association between suppression and interference must be sought in the process by which outer hair cell influence inner hair cell transduction.

Acoustic Stimulation