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. 2023 May 31;43(22):4093-4109.
doi: 10.1523/JNEUROSCI.2215-22.2023. Epub 2023 May 2.

Somatic Integration of Incoherent Dendritic Inputs in the Gerbil Medial Superior Olive

Affiliations

Somatic Integration of Incoherent Dendritic Inputs in the Gerbil Medial Superior Olive

Yarmo Mackenbach et al. J Neurosci. .

Abstract

The medial superior olive (MSO) is a binaural nucleus that is specialized in detecting the relative arrival times of sounds at both ears. Excitatory inputs to its neurons originating from either ear are segregated to different dendrites. To study the integration of synaptic inputs both within and between dendrites, we made juxtacellular and whole-cell recordings from the MSO in anesthetized female gerbils, while presenting a "double zwuis" stimulus, in which each ear received its own set of tones, which were chosen in a way that all second-order distortion products (DP2s) could be uniquely identified. MSO neurons phase-locked to multiple tones within the multitone stimulus, and vector strength, a measure for spike phase-locking, generally depended linearly on the size of the average subthreshold response to a tone. Subthreshold responses to tones in one ear depended little on the presence of sound in the other ear, suggesting that inputs from different ears sum linearly without a substantial role for somatic inhibition. The "double zwuis" stimulus also evoked response components in the MSO neuron that were phase-locked to DP2s. Bidendritic subthreshold DP2s were quite rare compared with bidendritic suprathreshold DP2s. We observed that in a small subset of cells, the ability to trigger spikes differed substantially between both ears, which might be explained by a dendritic axonal origin. Some neurons that were driven monaurally by only one of the two ears nevertheless showed decent binaural tuning. We conclude that MSO neurons are remarkably good in finding binaural coincidences even among uncorrelated inputs.SIGNIFICANCE STATEMENT Neurons in the medial superior olive are essential for precisely localizing low-frequency sounds in the horizontal plane. From their soma, only two dendrites emerge, which are innervated by inputs originating from different ears. Using a new sound stimulus, we studied the integration of inputs both within and between these dendrites in unprecedented detail. We found evidence that inputs from different dendrites add linearly at the soma, but that small increases in somatic potentials could lead to large increases in the probability of generating a spike. This basic scheme allowed the MSO neurons to detect the relative arrival time of inputs at both dendrites remarkably efficient, although the relative size of these inputs could differ considerably.

Keywords: binaural coincidences; distortion products; excitatory inputs; phase-locking; sound localization; vector strength.

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Figures

Figure 1.
Figure 1.
DZW stimulus. A, The DZW stimulus consisted of a total of 30 frequency components, which were distributed across ipsilateral (blue) and contralateral (red) ears. Its usage was combined with the complementary stimulus, in which the frequency components were swapped across the ears (not shown). In the monaural versions of this stimulus, either the contralateral or the ipsilateral components were left out. B, The zwuis stimulus played in this presentation to the contralateral ear consisted of a combination of pure tones, of which 10 ms of the first three (1, 3, 5) and the last (29) is shown. The (rounded) frequency (in Hz) of these four sine waves is given to the right of the traces. Bottom row represents the sum (Σ) of all 15 components. C, Same as in B, but illustrating the even components (2, 4, 6,…, 30) of the DZW stimulus, which, in this presentation, were played concurrently (Σ trace) to the ipsilateral ear.
Figure 2.
Figure 2.
Response to the DZW stimulus and analysis of subthreshold responses. A, Example of the response of an MSO cell (86604) to the DZW stimulus during a juxtacellular recording. Green bar represents auditory stimulation. B, Short segment of the recording extracted from underneath the blue square shown in A showing two sound-evoked APs marked by *. C, First derivative of the recording shown in B. Broken line indicates criterion for AP. The two APs are again marked by *. D, Frequency responses to 40 dB SPL DZW stimulation, as estimated from the Fourier spectrum of the response waveform (the high-pass filtered recorded potential) restricted to subthreshold activity (i.e., after the removal of the APs). Subthreshold response magnitudes were similar for binaural (filled symbols) and monaural (empty symbols) stimulation. In both cases, frequency components of the same presentation are connected, and each frequency is presented to both ears in consecutive presentations, referred to as Presentation 1 (triangles) and Presentation 2 (circles), respectively. Only components passing the Rayleigh test (see Materials and Methods) are shown here. In this and following figures, 0 dB corresponds to an amplitude of 1 mV. E, Corresponding phases of the subthreshold responses. Symbols have the same meaning as in D. Phases have been compensated for a delay of 4.3 ms. Same cell as shown in A-D.
Figure 3.
Figure 3.
Whole-cell recordings showed similar results as juxtacellular recordings. A, Example of the response to the DZW stimulus of an MSO cell (86108) recorded in the whole-cell configuration. Green bar represents auditory stimulation. B, Short segment of the recording extracted from underneath the blue square shown in A. *Single spike. C, First derivative of the recording segment shown in B. *Single spike. Broken horizontal line indicates the AP criterion. D, Frequency responses to 40 dB SPL DZW stimulation, as estimated from the Fourier spectrum of the response waveform of the same cell as shown in A-C. Response magnitudes were similar for binaural (filled symbols) and monaural (empty symbols) stimulation. In both cases, frequency components of the same presentation are connected, and each frequency is presented to both ears in consecutive presentations, referred to as Presentation 1 (triangles) and Presentation 2 (circles), respectively. E, Phases of the phase-locked responses to the different frequencies in the DZW stimulation. Symbols have the same meaning as in D. Phases have been compensated for a delay of 5.2 ms.
Figure 4.
Figure 4.
Comparison of subthreshold responses elicited by binaural and monaural DZW stimuli. A, Difference in magnitude of responses to binaural and monaural DZW stimulation of the cell shown in Figure 1. Positive values signify larger amplitudes for binaural stimulation. B, Companion phase differences. C, Difference in the magnitude of the response to monaural and binaural DZW stimulation for a population of cells. Juxtacellular recordings (n = 65) and whole-cell recordings (n = 6) were pooled as results were similar for both methods. Each dot represents the difference in the response to a single primary component in a cell during binaural versus monaural DZW stimulation; for positive values, the binaural response was larger than the monaural response. Closed circles represent the averages of all responses in 100 Hz bins; for display purposes, the contralateral average responses have been slightly shifted in A and B. D, Same as in C, but the phase of the response to monaural and binaural DZW stimulation was compared. Positive values correspond to a phase lead of the binaural response. E, Same as in C, but the stimulus frequencies are shown relative to the best frequency of each cell. F, Same as in D, but frequencies were normalized as in E.
Figure 5.
Figure 5.
Differences in subthreshold responses to monaural and binaural DZW were reduced at a lower sound intensity. A, Magnitude of responses to monaural and binaural DZW stimuli at 40 dB SPL (cell 81203). At all frequencies, responses to ipsilateral stimulation were clearly smaller for monaural than for binaural stimulation. B, Phase of response to monaural and binaural stimuli at 40 dB SPL for the same cell. Phases were compensated for a delay of 5.0 ms. C, Same as in A, but stimulus intensity was 30 dB SPL. The difference in the responses for the monaural and binaural ipsilateral stimulation condition is strongly reduced. D, Same as in B, but stimulus intensity was 30 dB SPL. E, Comparison of the difference in responses to monaural and binaural stimuli presented at 30 and 40 dB SPL in 17 cells. Differences were smaller for stimuli at 30 dB SPL. Squares represent 81203 used in A-D. Diamonds represent cell 89002 (whole-cell recording), which behaved similarly as cells with juxtacellular recordings.
Figure 6.
Figure 6.
Spike responses to monaural and binaural DZW. A, Comparison of spike rates evoked by monaural ipsilateral and contralateral stimuli plotted on a cubic root scale (n = 71). Solid black line indicates the identity line. Dotted lines indicate a 10 times larger spike rate for one ear. A, B, Monaural spike rates were adjusted for spontaneous firing as described in Materials and Methods. B, Comparison of spike rate in response to binaural stimuli and the sum of spike rates in response to ipsilateral and contralateral stimuli (n = 71, including 7 cells with very few spikes). Solid line indicates an orthogonal linear regression (y = 0.99x + 0.15). C, Comparison of facilitation index (binaural spike rate vs summed monaural spike rates) and binaurality index (contralateral monaural spike rate vs summed monaural spike rates) (n = 70 cells). Gray line indicates the regression line (y = −0.25x + 1.28; r = −0.11; p = 0.39). One outlier point with low firing rates and a facilitation index of 8 is not shown and was not taken into account in the fit.
Figure 7.
Figure 7.
Phase-locking to the individual components of the zwuis stimulus. A, VS versus frequency. Significant ipsilateral (blue) and contralateral (red) components are shown for monaural (open symbols) and binaural (closed symbols) DZW stimulation. B, Magnitude of subthreshold components (compare Fig. 2D) obtained from the same recording. C, Crosses (n = 12) represent VS to the contralaterally presented components compared between monaural and binaural stimuli. This comparison assesses how phase-locking to the contralateral stimulus is affected by presenting an uncorrelated stimulus to the ipsilateral ear. Unity line (solid black line) is the prediction of a perfect coincidence detector. Dashed line indicates the prediction in case of spike-train superposition (see Materials and Methods). Red line indicates the fit SC = βCSB, with βC = 0.85. θC, the normalized βC, was 0.66. D, Same as in C, but with the ears reversed. Blue line indicates the fit SI = βISB with βI = 0.90. θI, the normalized βI, was 0.78. E, Population data of the relation between θI and θC. Open circles represent cells with good ITD tuning (n = 7). *Cells for which recording duration did not permit to test ITD tuning (n = 6).
Figure 8.
Figure 8.
Neurons driven by only one ear can nevertheless have good ITD tuning. A, VS of DZW components of a cell (90004) that phase-locked only to contralateral stimulation. Empty red symbols represent contralateral stimulation. Filled red symbols represent contralateral components during binaural stimulation. B, Subthreshold frequency response. C, ITD tuning curve obtained using noise stimuli presented at different ITDs. D, Binaural disparity between the number of significant VS components was not correlated with the BITD measured in the same cells. Open symbols represent monaural stimulation (n = 31 cells). Closed symbols represent binaural DZW stimulation (n = 33 cells). Gray line indicates the regression line for the monaural data (y = −0.02x + 0.135; r = −0.07; p = 0.69). Square represents the cell that is illustrated in A-C.
Figure 9.
Figure 9.
Evidence of nonlinearity in spiking response to DZW stimulus. A, VS of DZW components presented contralaterally (cell 84203). VS was obtained from the Fourier transform of binary spike data. Small filled circles represent the primary components in the auditory stimulus (“Contra mon”). Horizontal gray line indicates the threshold for significance; primaries above this line are shown as a filled circle with a larger circle. Triangles represent the DP2s where both f1 and f2 were in the same ear (i.e., monodendritic DP2s, “Contra DP2”). Only DP2s whose VS was significant have been marked. The response to only one of the two DZW stimulus sets is shown; the other set of frequencies produced similar results. B, Same as in A, but stimulation was ipsilateral. C, Same as in A, but stimulation was binaural. Green asterisks represent the bidendritic DP2s (“Bin DP”), for which f1 and f2 were presented in different ears. D, Magnitude of subthreshold components obtained from the same recording as illustrated in A-C.
Figure 10.
Figure 10.
Distribution of significant subthreshold and suprathreshold primary and DP2 components. A, Stacked bar plot represents the distribution of different types of significant primary components as a function of their tone frequencies. The height of the light brown part of the bar indicates the fraction of the total number of primary components in each bracket of frequencies resulting in significant subthreshold activity, but not a significant VS. Blue represents fraction of primary components with only significant VS. Dark brown represents both subthreshold and suprathreshold components significant. Data from 71 cells were pooled. B, Same as in A, but for bidendritic DP2s. C, Same as in A, but for monodendritic DP2s.
Figure 11.
Figure 11.
Comparison of the total power of subthreshold and suprathreshold primary and DP2 components evoked by binaural DZW stimulation. A, Power of subthreshold DP2 activity relative to primary activity (n = 71 cells). B, Power of subthreshold bidendritic DP2 activity relative to the monodendritic DP2 activity (n = 21 cells). C, Power of suprathreshold DP2 activity relative to the primary suprathreshold activity (n = 49 cells). D, Power of subthreshold bidendritic DP2 activity relative to the monodendritic DP2 activity (n = 27 cells).
Figure 12.
Figure 12.
Spike triggering efficacy for monaural and binaural DZW stimulation. A, Relation between VS and the size of the phase-locked response for different frequencies in the DZW stimulus. Only points with both significant VS and significant subthreshold amplitude are shown. Solid lines indicate the regression lines through the origin. In this neuron (92801), spike triggering efficacy was similar for ipsilateral and contralateral inputs. B, Relation between spike triggering efficacy for monaural and binaural ipsilateral (n = 27 cells) or contralateral (n = 35 cells) stimulation. Triangle represents the cell illustrated in A. Spike triggering efficacy was obtained as in A.
Figure 13.
Figure 13.
Spike triggering efficacy can be substantially different for ipsilateral and contralateral inputs. A, Relation between VS and the size of the phase-locked response for different frequencies in the DZW stimulus. Solid lines indicate the regression lines through the origin. In this neuron (91307), for both the monaural and binaural stimulus, ipsilateral inputs were associated with higher VSs than contralateral inputs of similar size. B, Histogram represents a comparison of the relative spike triggering efficacy for contralateral and ipsilateral stimuli in a population of cells (n = 33). Slopes were obtained as illustrated in A. The relative slope was calculated from the slopes of the ipsilateral and contralateral components during binaural DZW stimulation. Circle and triangle represent the relative slopes obtained for the cell illustrated in A and in Figure 12A, respectively.
Figure 14.
Figure 14.
Lower spike triggering efficacy is associated with larger suprathreshold EPSPs. A, Measurement of maximum rate of rise of suprathreshold EPSP and EPSP-AP delay. B, Scatterplot represents the relation between EPSP-AP delay and the maximum rate of rise of suprathreshold EPSPs during ipsilateral monaural stimulation (blue; n = 132), contralateral monaural stimulation (red; n = 104), or binaural DZW stimulation (black; n = 466) for the same cell as in A. Broken lines indicate median values. Solid lines indicate regression lines showing that larger EPSPs trigger APs more rapidly. C, Cumulative plots of suprathreshold EPSPs for the same data as shown in B. D, Cumulative plots of EPSP-AP delays for the same data as shown in B. The horizontal line intersects with the median delay. E, Relation between the relative size of the median EPSP slope and the relative size of the spike triggering efficacy. Solid line indicates the regression line (y = −0.15x + 0.57; r = −0.56; p = 0.007; n = 23). Triangle represents the cell illustrated in A-D. F, Relation between the difference in the median EPSP-AP delay during contralateral and ipsilateral monaural DZW stimulation and the relative size of the spike triggering efficacy. Solid line indicates the regression line (y = −0.05x + 0.02; r = −0.38; p = 0.072; n = 23). Triangle represents the cell illustrated in A-D.

References

    1. Agmon-Snir H, Carr CE, Rinzel J (1998) The role of dendrites in auditory coincidence detection. Nature 393:268–272. 10.1038/30505 - DOI - PubMed
    1. Batra R, Kuwada S, Fitzpatrick DC (1997) Sensitivity to interaural temporal disparities of low- and high-frequency neurons in the superior olivary complex: II. Coincidence detection. J Neurophysiol 78:1237–1247. 10.1152/jn.1997.78.3.1237 - DOI - PubMed
    1. Biedenbach MA, Freeman WJ (1964) Click-evoked potential map from the superior olivary nucleus. Am J Physiol 206:1408–1414. 10.1152/ajplegacy.1964.206.6.1408 - DOI - PubMed
    1. Brand A, Behrend O, Marquardt T, McAlpine D, Grothe B (2002) Precise inhibition is essential for microsecond interaural time difference coding. Nature 417:543–547. 10.1038/417543a - DOI - PubMed
    1. Clark GM, Dunlop CW (1968) Field potentials in the cat medial superior olivary nucleus. Exp Neurol 20:31–42. 10.1016/0014-4886(68)90122-2 - DOI - PubMed

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