A Test of the Stereausis Hypothesis for Sound Localization in Mammals

Abstract

The relative arrival times of sounds at both ears constitute an important cue for localization of low-frequency sounds in the horizontal plane. The binaural neurons of the medial superior olive (MSO) act as coincidence detectors that fire when inputs from both ears arrive near simultaneously. Each principal neuron in the MSO is tuned to its own best interaural time difference (ITD), indicating the presence of an internal delay, a difference in the travel times from either ear to the MSO. According to the stereausis hypothesis, differences in wave propagation along the cochlea could provide the delays necessary for coincidence detection if the ipsilateral and contralateral inputs originated from different cochlear positions, with different frequency tuning. We therefore investigated the relation between interaural mismatches in frequency tuning and ITD tuning during in vivo loose-patch (juxtacellular) recordings from principal neurons of the MSO of anesthetized female gerbils. Cochlear delays can be bypassed by directly stimulating the auditory nerve; in agreement with the stereausis hypothesis, tuning for timing differences during bilateral electrical stimulation of the round windows differed markedly from ITD tuning in the same cells. Moreover, some neurons showed a frequency tuning mismatch that was sufficiently large to have a potential impact on ITD tuning. However, we did not find a correlation between frequency tuning mismatches and best ITDs. Our data thus suggest that axonal delays dominate ITD tuning.SIGNIFICANCE STATEMENT Neurons in the medial superior olive (MSO) play a unique role in sound localization because of their ability to compare the relative arrival time of low-frequency sounds at both ears. They fire maximally when the difference in sound arrival time exactly compensates for the internal delay: the difference in travel time from either ear to the MSO neuron. We tested whether differences in cochlear delay systematically contribute to the total travel time by comparing for individual MSO neurons the best difference in arrival times, as predicted from the frequency tuning for either ear, and the actual best difference. No systematic relation was observed, emphasizing the dominant contribution of axonal delays to the internal delay.

Keywords: auditory; cochlear disparity; interaural time difference; internal delay; medial superior olive; sound localization.

Figure 1.

Cochlear time delays. A, Traveling wave wavelength dependence on the characteristic frequency in the cochlea for three different species: chinchilla (Temchin et al., 2012), cat (van der Heijden and Joris, 2006), and guinea pig (Palmer and Shackleton, 2009); circles, squares, and triangles, respectively). Solid line shows the linear fit for all three species. B, Theoretical cochlear time delay dependence on frequency mismatch between the ears for six different characteristic frequencies. Relationships were derived from linear fit in A.

Figure 2.

Determining BITDs of MSO neurons. A, Loose-patch (juxtacellular) recording of an MSO neuron during binaural stimulation with 300 ms zwuis stimulus (gray bar) at 30 dB SPL. The gray portion of the waveform is shown at higher time resolution below, revealing subthreshold events and action potentials (*) during stimulation. B, Example of a rITDf, showing firing rate as a function of ITD (positive ITD values: contralateral leading). Circles indicate measured spike rates; gray line is a cubic spline through the data points. BITD was 0.17 ms (vertical line). Same cell as A. C, Cumulative histogram plots of BITDs. The gray area indicates the physiological ITD range for a gerbil (±0.13 ms). In 60 of 68 cells, BITDs were biased toward contralateral ear leading.

Figure 3.

Composite ITD curves from tonal data. A, Superimposed tonal ITD curves at six different frequencies. Average BF of the neuron at 40 dB SPL was 0.78 kHz. Line thickness indicates tone frequency, varying in 100 Hz steps from 400 (thickest line) to 900 Hz. B, Composite ITD curve (circles) was obtained by adding the six tone responses shown in A. Solid line is fit with a Gabor function. Vertical line indicates the BITD (0.11 ms). C, Wideband ITD curve (circles) and fitted Gabor function (solid line) for the same cell as shown in B. Vertical line indicates BITD (0.04 ms). D, Comparison of BITDs from wideband rITDfs and from tonal stimulation composite ITD curves (N = 26; r = 0.85; p < 0.0001). Gray line indicates identity; only BITDs with estimated SD <0.25 ms were used. Highlighted symbol corresponds to the cell shown in B and C.

Figure 4.

Binaural MSO sensitivity to electrical round window stimulation. A, Schematic representation of the two stimulation methods. Blue and red trapezoids symbolize ipsilateral and contralateral cochleae, respectively. Speaker icons indicate sound stimulation at the base of cochlea; bolt icons indicate electrical stimulation which bypasses the traveling wave. Two arrows pointing toward MSO cell represent neural pathways converging onto MSO. B, Monaural and binaural MSO responses to electrical round window stimulation. Red, blue, and gray traces show responses to contralateral-only, ipsilateral-only, and both ear stimulation, respectively. Each set of traces shows five instances of individual responses and the black trace is an average of a total of 10 repetitions. The three groups of traces were displaced with respect to each other in the vertical direction for visual clarity. The asterisk on the bottom trace indicates the location of two evoked action potentials. Arrows indicate the beginning of stimulus; stimulus artifacts were cut out for demonstrational purposes. C, Comparison of rITDfs from wideband auditory and electrical round window stimulation data. Circles indicate data points, lines are interpolated values. The left ordinate shows how many spikes on average were evoked by a single electrical stimulus, thus providing the current stimulation rITDf. The right ordinate show the spike rates evoked by the auditory stimulus (auditory rITDf). BITDs for the three cells from left to right (auditory vs electrical): −0.12 versus −0.32 ms, −0.01 versus 0.21 ms, 0.38 versus 0.12 ms.

Figure 5.

Determining the characteristic frequency of an MSO neuron. A, Individual monaural responses to zwuis stimuli presented at different sound intensity levels. Responses to different SPLs are represented by different colors; the numbers indicate SPL per tone component. Symbols show the measured data points; solid lines, the fits. Left and right plots show responses for contralateral and ipsilateral ear, respectively. Gray area demarcates the threshold where the response cannot be distinguished from the noise floor (see Materials and Methods). Red vertical lines indicate the characteristic frequencies, determined at 10 dB SPL stimulus intensity; CFs for contralateral and ipsilateral ears were 0.78 and 0.74 kHz, respectively. B, Monaural receptive fields of the MSO neuron determined using zwuis stimulus presented at different sound intensities (in 10 dB steps). Left and right plots show receptive fields for contralateral and ipsilateral ear, respectively.

Figure 6.

Frequency mismatch estimation. A, MSO neuron's frequency responses to contralateral (filled circles) and ipsilateral (open squares) stimulation at 10 dB SPL, estimated from the Fourier spectrum of the response waveform (compare Fig. 5A). Gray area indicates the noise floor. B, Normalized cross-correlation function of the two frequency responses shown in A. The gray vertical bar indicates the peak of the curve, revealing that the contralateral ear has an estimated 56 Hz higher CF. The data for A and B were taken from the same cell as Figure 5. C, Histogram of characteristic frequency mismatches between ipsilateral and contralateral stimulation (N = 78). D, Relation between interaural CF mismatches and mean CF of both ears for all MSO cells (N = 78; r = −0.17; p = 0.13). E, Distribution of cochlear time delays calculated from measured frequency mismatches (N = 78). F, Relation between basilar membrane mismatches, calculated using Müller (1996) and CF (N = 78; r = −0.10; p = 0.35).

Figure 7.

Correlation between monaural frequency tuning within and across MSO cells. A, Relation between contralateral and ipsilateral BFs of MSO neurons at a stimulus intensity of 30 dB SPL (N = 69; r = 0.94; p < 0.0001). Seventeen neurons were not included as they were not sensitive to the 30 dB SPL stimulus. Solid line indicates identity. B, Cumulative histogram plots of the normalized correlation coefficients between monaural receptive fields. Thick black line: contralateral and ipsilateral receptive fields from the same MSO neuron (C/I, same cell; N = 84). Gray line: contralateral and ipsilateral fields from all pairs of MSO cells (C/I, across cells). Broken line: contralateral receptive fields between all pairs of MSO cells (C/C, across cells).

Figure 8.

Inverse relation between BITD and mean CF. A, Cells tuned to low CFs tend to have more positive BITDs; black line shows linear regression (N = 40; r = −0.57; p = 0.0004). B, Comparison of BITD and mean CF correlation in Mongolian gerbils for four studies (and their stimulus): Day and Semple (2011) (binaural beat tone stimuli at BF); Brand et al. (2002)(FM tones at BF); Pecka et al. (2008)(tones at BF); and this study (the same data as in A). Dashed lines indicate gerbil's physiological ITD range.

Figure 9.

Relation between BITDs and frequency tuning mismatches of MSO neurons. CF mismatches were determined using cross-correlation of responses to zwuis stimuli (Fig. 6). A, Relation between BITD and CF mismatch (N = 40). Bars indicate SD. B, Relation between BITD and predicted BITD. Predicted BITD was obtained from the relation between the traveling wavelength and CF (Fig. 1A). Bars indicate combined SD in BITD and predicted BITD. Line shows linear regression (slope −0.22 ms/ms; r = −0.012; N = 40). C, Results of bootstrap analysis of the slope of the regression line of the relation between BITD and predicted BITD. Gray line (random) shows distribution of slopes when BITD values were scrambled; black line (data fit) shows fit slopes when data points were drawn from a distribution with the same mean as the measured BITD and its combined error; dashed line (stereausis) shows distribution of fit slopes when data points were drawn from a distribution with the same mean as the predicted BITD and the combined error.