 |
INTRODUCTION |
Ongoing interaural temporal disparities (ITDs) are a major cue for localization of sounds along the azimuth (Wightman and Kistler 1997
). In the inferior colliculus (IC) there are neurons sensitive to ITDs in low-frequency sounds (;lr2 kHz) (e.g., Kuwada et al. 1979
, 1987
; Rose et al. 1966
; Roth et al. 1978
; Stillman 1971
) and neurons sensitive to ITDs in envelopes of high-frequency sounds (e.g., Batra et al. 1989
; Crow et al. 1980
; Yin et al. 1984
). Some of the neurons sensitive to ITDs in low-frequency sounds appear to encode a particular ITD by discharging maximally at this ITD at all frequencies to which they are sensitive. We refer to such neurons as "peak-type" neurons. Other neurons encode a particular ITD by discharging minimally. We refer to such neurons as "trough-type" neurons. However, the responses of many peak- and trough-type neurons in the IC are irregular in that the ITD at which delay curves at different frequencies align does not lie precisely at the peak or the trough or in that there is considerable jitter in the ITD that evokes maximal or minimal discharge (Kuwada et al. 1987
). Similarly, neurons in the IC that are sensitive to ITDs in envelopes of high-frequency sounds can be of the peak type or the trough type, and neurons of both types can exhibit irregularities (Batra et al. 1993
).
The ITD sensitivity of neurons in the IC is presumably inherited from centers lower in the brain stem (Batra et al. 1989
; Stanford et al. 1992
). Thus irregularities in the responses of these neurons may be due to the convergence of inputs from lower centers. The superior olivary complex (SOC) is the main site in the brain stem where neural signals from the two ears are compared to generate a sensitivity to ITDs. Both principal binaural nuclei of the SOC, the medial and lateral superior olives (MSO and LSO, respectively) receive binaural input and contain neurons sensitive to ITDs (Caird and Klinke 1983
; Finlayson and Caspary 1991
; Goldberg and Brown 1969
; Joris and Yin 1995
; Langford 1984
; Spitzer and Semple 1995
; Yin and Chan 1990
). However, the MSO and LSO receive different types of inputs and so are likely to encode ITDs in different ways. Most neurons of the MSO are excited by acoustic stimulation of either ear (Caird and Klinke 1983
; Goldberg and Brown 1968
; Guinan et al. 1972a
,b
; Langford 1984
; Yin and Chan 1990
). These neurons are believed to encode ITDs by firing maximally at the ITD for which the temporal pattern of the discharge arriving from both sides is in coincidence (Goldberg and Brown 1969
; Jeffress 1948
), resulting in a peak-type response. In contrast, most neurons of the LSO are excited by ipsilateral stimulation but inhibited by contralateral stimulation (Boudreau and Tsuchitani 1968
; Caird and Klinke 1983
; Covey et al. 1991
; Finlayson and Caspary 1989
; Guinan et al. 1972a
,b
; Harnischfeger et al. 1985
; Moore and Caspary 1983
; Sanes 1990
; Tsuchitani 1977
; Wu and Kelly 1991
). These neurons should encode ITD by being maximally suppressed at the ITD at which coincidence occurs (Kuwada et al. 1987
; Yin and Kuwada 1983b
), resulting in a trough-type response.
Previous studies (Joris 1996
; Spitzer and Semple 1995
; Yin and Chan 1990
) have reported neurons in the vicinity of the MSO with peak-type responses to ITDs both in the fine structure of low-frequency sounds and in the envelopes of high-frequency sounds. Trough-type neurons sensitive to ITDs in the envelopes of high-frequency sounds have been reported in the LSO (Joris 1996
). However, no population of trough-type neurons in the SOC sensitive to ITDs in the fine structure has yet been reported, despite a search for such neurons by Spitzer and Semple (1995)
.
In this study we recorded from ITD-sensitive units in the SOC of the unanesthetized rabbit. In the first paper of this two-part series we demonstrate that, consistent with our expectations, there were both peak-type and trough-type units sensitive to ITDs in the fine structure of low-frequency sounds and in the envelopes of high-frequency sounds. Contrary to our expectations, we found many units in the SOC that had irregular responses, suggesting an unanticipated degree of complexity at the first stage of ITD representation. In the second paper (Batra et al. 1997
) we demonstrate that all types of units in the SOC act as coincidence detectors.
 |
METHODS |
Surgery and recording
Eight female Dutch-belted rabbits (~2 kg) with clean external ears were used in these experiments. Surgical and recording procedures were the same as previously described (Batra et al. 1993
; Kuwada et al. 1987
). Each rabbit was surgically prepared for recording in three steps. During each step the rabbit was anesthetized with a mixture of ketamine and xylazine (35 and 5 mg/kg im, respectively). In the first step, the dorsal surface of the skull was surgically exposed with the use of aseptic techniques. A short brass rod of square stock was mounted on the left side, parallel to the sagittal suture, with screws and dental cement. The right side of the skull was left exposed between lambda and bregma to allow electrodes to be lowered to the right SOC. In one case, the bone over the left SOC was also left exposed. The rabbit was then allowed several days to recover. In the second step, custom ear molds were made of Audalin (Esschem, Essington, PA), an ear-impression compound. Each ear mold was penetrated by a tube through which sound could be delivered. The tubes for the two ears were matched in length.
After the second step, 1-2 wk were spent acclimating the rabbit to body and head restraint and to the ear molds. The rabbit was zipped into a body stocking and held in a Plexiglas couch with nylon straps. The head was held stationary by clamping the brass rod. After a few sessions in the couch, the ear molds were inserted. The acclimation procedure was performed in the soundproof booth in which recording sessions were held.
The third step was to drill a small hole (2-4 mm) in the skull just rostral to lambda to permit passage of the electrode. A topical antibiotic was then applied to the exposed dura, and the hole was capped with elastopolymer.
During a recording session, the rabbit was restrained as described above, the elastopolymer cap was removed, and the exposed dura was desensitized with lidocaine. The dura was then pierced with a hypodermic needle (23-gauge) inside which rode the electrode (glass-coated Pt-Ir or Pt-W). The electrode was advanced with the use of a Burleigh microdrive, which, along with data collection and acoustic stimulation, was controlled from outside the booth. During the session, the rabbit was monitored with the use of a video camera. Each session usually lasted 2-3 h, but if the rabbit fidgeted the session was terminated.
Acoustic stimulation
The sensitivity of units to ITDs of pure low-frequency tones was tested with a "binaural-beat" stimulus (Kuwada et al. 1979
). In this paradigm, tones that differed in frequency by 1 Hz were delivered to the two ears, with the frequency to the contralateral ear usually higher. This stimulus produced a 1-Hz cyclic variation in the ongoing ITD. Units sensitive to ITDs in the fine structure were typically tested only below 2 kHz. The "best binaural-beat frequency" was taken to be the frequency at which the response to the binaural-beat stimulus was maximal. The sensitivity of units to ITDs in high-frequency sounds (>2 kHz) was tested in a similar manner with the use of sinusoidally amplitude-modulated (SAM) tones. In this case, the tones at the two ears were set to the same carrier frequency, usually at or near the best frequency of the unit, or at an effective frequency if they were broadly tuned. The best frequency of these units was assessed with the use of monaural (usually ipsilateral) tones at a fixed suprathreshold intensity presented over a wide range of frequencies. The modulation frequencies at the two ears differed by 1 Hz (Batra et al. 1989
; Yin et al. 1984
), again with the frequency to the contralateral ear usually higher. This stimulus produced a 1-Hz cyclic variation in the ITD of the envelope, but no variation in the ITD of the carrier. The ITD of the carrier was zero relative to the standard calibration (see below). All tones and tone bursts had linear rise/fall times of 4 ms. For the sake of brevity, we often refer to "low-frequency units" or "high-frequency units," depending on whether sensitivity of the unit to fine-structure or envelope ITDs was tested. This should cause no confusion, because only one unit was tested with both kinds of stimuli.
The SAM tones were usually modulated to a depth of 80% and presented at a suprathreshold intensity of ~30-70 dB SPL relative to the standard calibration (see below). The interaural level difference was usually set to zero relative to this calibration. Both kinds of stimuli were 5.1 s long. The first 100 ms of the response was not analyzed to avoid onset effects. Period histograms of the response as a function of the interaural phase difference were constructed; these were then replotted as a function of the equivalent ITD (Kuwada et al. 1987
; Yin and Kuwada 1983b
). The period histograms had 10 bins.
During the experiment the sound intensities and phases were set relative to a standard calibration. After the last recording session with each rabbit, the true calibration in dB SPL (re 20 µPa) was measured with the use of a calibrated microphone and probe. The probe was inserted through a hole drilled in the wall of the bony external meatus. The gap around the hole was sealed before calibrations were performed. In earlier experiments, the calibration was performed after the animal had been killed. In later experiments, calibrations were measured with the animal deeply anesthetized. Calibrations were taken in 20-Hz steps from 60 Hz to 40 kHz. The signal from the microphone was digitized and the amplitude and phase were calculated. In a few cases the ear molds were removed and reinserted and the calibration was repeated.
The mean phases and mean interaural phases of responses to pure tones were corrected by subtracting the difference in phase between standard and true calibrations at the relevant frequency. Variation in intensity across frequencies was accounted for as previously described (Kuwada et al. 1987
). The acoustic delay for signals to reach the tympanum was 216 ± 12 (SD) µs (n = 16, estimated from the slope of the phase-vs.-frequency plot). The average difference between the ears was 5.0 ± 9.6 µs, with the delay for the right ear nominally longer. Calibration corrections for the phases of responses to SAM tones were not performed; however, the intensities quoted in the figure legends were corrected to reflect the true levels in dB SPL.
Localization of recording sites
For each electrode penetration, the position of the electrode was set relative to a reference mark on the skull. The depth at which each unit was studied was recorded. During the last recording session, electrolytic lesions were made at selected sites (10 µA for 10-20 s). In some cases the animal was killed and the brain was fixed by immersion, whereas in other cases the animal was deeply anesthetized and then perfused with a 10% solution of formol saline. The brain was sectioned and stained with cresyl violet or thionin (Kuwada et al. 1987
).
Analysis
ASSESSMENT OF BINAURAL RESPONSE TYPE.
The ipsilateral and contralateral input to a unit was evaluated with the use of one of two techniques. The first technique was used with low-frequency units and some high-frequency units. In this technique, the response of the unit to monaural tone bursts was visually assessed and also quantitatively analyzed to determine whether it responded to the tone and whether the response during the stimulus interval was excitatory or inhibitory. The quantitative analysis was performed to objectively demarcate weak excitation or inhibition from the absence of a response. We restricted this analysis to records for which the stimulus duty cycle was
50%, because it was difficult to distinguish weak excitation or inhibition when the off-time was brief. From each record, a "repetition-interval synchronization coefficient" and a "repetition-interval phase" were calculated by treating the repetition interval of the tone as the period of a cyclic stimulus. A repetition-interval synchronization coefficient that was significant (Rayleigh test of uniformity, P < 0.001) (Mardia 1972
) denoted a response that followed the stimulus. Excitation was distinguished from inhibition by examining the repetition-interval phase. A phase less than the duty cycle implied excitation, whereas a phase greater than the duty cycle implied inhibition. An exception to this rule was responses with repetition-interval phases that exceeded 0.85 cycles or that corresponded to times that were shorter than the latency of the unit (e.g., Fig. 6 A and B, left). Such responses invariably consisted of transient excitation followed by sustained inhibition and were classified as complex.

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| FIG. 6.
Responses of high-frequency peak-type and trough-type neurons to monaural stimulation. A and B: same 2 peak-type neurons as in Fig. 2, A and B. C and D: same 2 trough-type neurons as in Fig. 2, C and D. In D, left, contralateral stimulation ( ) is superimposed on an ongoing ipsilateral stimulus. Insets in A and B: same responses plotted with a coarser binwidth to demonstrate sustained inhibition. Insets in C and D: 1st 20 ms of response. Each plot illustrates a full repetition interval. Stimulus durations (ms) and number of repetitions (contralateral/ipsilateral): 50, 50/50 (A); 75, 100/150 (B); 50, 75/75 (C); 50 (contra) + 150 (ipsi)/50, 20/100 (D). Intensities and frequencies as in Fig. 2. Binwidth: 5 ms (A and B, insets), 500 µs (D, contralateral), and 200 µs elsewhere.
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For high-frequency units, a different paradigm was often used. An excitatory input was first identified with the use of monaural pure tones as described above. The input from the opposite side was then tested by varying the intensity of a pure tone to that side while concurrently stimulating the excitatory side with a tone of fixed intensity (e.g., Fig. 6D, left). The latter technique is better at detecting inhibitory inputs, because it provides background activity that can be suppressed. However, its use at low frequencies is problematic, because at these frequencies the inputs are phase locked, and whether facilitation or suppression is observed can depend on the ITD. Furthermore, at low frequencies, facilitation need not imply the presence of bilateral excitatory inputs or suppression of the presence of inhibition. Finlayson and Caspary (1991)
have suggested that the facilitation observed in some neurons of the LSO is a consequence of rebound excitation. Conversely, Colburn et al. (1990)
have argued that the suppression observed in neurons of the MSO can be adequately modeled without resorting to inhibitory inputs.
PHASE PLOTS.
For each unit, a phase plot of the mean interaural phase of the response at different frequencies (or modulation frequencies, for SAM tones) was constructed. The mean interaural phase is the circular mean of the interaural phases (or modulation phases) at which action potentials occur (Kuwada et al. 1987
; Yin and Kuwada 1983a
). The phase plots were fit with a straight line with the use of a least-squares procedure (Kuwada et al. 1987
). Each phase value was weighted by the product of the interaural synchronization coefficient and the mean rate to reduce the effect of responses at frequencies for which sensitivity to ITDs was weak.
The linearity of phase plots, and deviations from linearity, were assessed with the use of several techniques. The linearity criterion of Yin and Kuwada (1983b)
compares the mean square error (MSE) of deviations about the fit with that obtained from a random simulation. If the MSE is less than that obtained from the simulation for a particular significance level (P < 0.005), then the phase plot is considered significantly linear. The
2 test used by Kuwada et al. (1987)
1 compares the MSE with the average variability of the measurements of the mean phases. If the MSE is significantly greater (P < 0.005) than the average variability, then the phase plot is considered to deviate significantly from linearity. We also used a one-sample runs test (Siegel 1956
) to examine systematic patterns of deviations about the fit. This procedure examines the number of runs of values in a sequence that are greater or less than some criterion. It then tests whether the number of runs is more or fewer than statistically expected (P < 0.05). We applied this runs test to ascertain whether there was a systematic pattern of deviations about the fit, i.e., whether a phase plot contained a statistically low number of runs. Our usage differs from that intended in two regards. First, the test is intended to be applied to a situation in which the point from which positive and negative deviations are measured is independent of the data. Our use of the fitted line as the zero point is not in accord with this condition. In our situation, at least three runs of deviations had to occur, because the fit has two parameters (intercept and slope). Consequently, the likelihood of a low number of runs in our situation is even lower than for the test as described. Second, phase plots for which the number of runs were greater than expected were not considered significant, because this was the more conservative approach. These two factors imply that our significance level is more strict than P < 0.05. The runs test requires a large number of measurements, so this analysis was restricted to units for which the response was measured at
11 frequencies.
 |
RESULTS |
We recorded from 124 single neurons and multiunit clusters that were sensitive to ITDs. Of these, 100 were sensitive to ITDs in the fine structure of low-frequency tones (43 neurons, 57 multiple units) and 25 were sensitive to ITDs in the envelopes of SAM tones with high-frequency carriers (21 neurons, 4 multiple units). The responses of one neuron to both types of ITDs were studied; that neuron is therefore included twice in statistics and plots that combine high-frequency and low-frequency responses. At the time each neuron or multiunit cluster was studied, we visually assessed whether or not the recording was contaminated with the neurophonic that is present in the SOC. No unit for which recordings were contaminated with neurophonic are included here. All illustrated responses are those of single neurons; multiunit responses are included only in histograms and scatter plots. We saw no clear differences between responses of neurons and multiple units.
Peak-type and trough-type units: general characteristics
Both peak-type and trough-type neurons were present in the SOC. Responses of four neurons sensitive to ITDs of low-frequency tones are illustrated in Fig. 1.

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| FIG. 1.
Sensitivity of 4 neurons in the superior olivary complex (SOC) to interaural temporal disparities (ITDs) of low frequencies. Left: response as a function of ITD at selected frequencies. Functions were generated from the responses to binaural-beat stimuli (Kuwada et al. 1987 ; Yin and Kuwada 1983b ). The neurons of A and B exhibited peak-type sensitivity to ITDs in that the maximal response occurred at about the same ITD at all frequencies. The neurons of C and D exhibited trough-type sensitivity to ITDs in that the response was minimal at about the same ITD at all frequencies. Right: peak- or trough-type sensitivity of these neurons was confirmed by their phase plots, which show the mean interaural phase of the response at different frequencies. The mean interaural phase is the circular mean of the interaural phases at which action potentials occurred (Kuwada et al. 1987 ; Yin and Kuwada 1983a ). The line is a weighted least-squares fit. In A and B, the fit indicates that the characteristic phase (CP), given by the intercept, is near 0 cycles, confirming that the neuron responded maximally at about the same ITD across frequencies. In C and D, the CP is near 0.5 cycles, confirming that the response of the neuron was minimal at about the same ITD across frequency. Because the CP is an angular measurement, its value can be quoted only over 1 complete cycle of phase change. Here we take the CP to lie between 0.25 and 0.75 cycles. The characteristic delay (CD), equal to the slope of the phase plot, lies near the common peaks (A and B) or troughs (C and D) of the delay curves (left, arrowheads). Best binaural-beat frequencies and average contralateral (re: site of recording)/ipsilateral intensity levels (dB SPL): 850 Hz, 64/64 (A); 700 Hz, 52/53 (B); 400 Hz, 64/65 (C); 350 Hz, 64/65 (D).
|
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Figure 1, left, illustrates the response of each neuron as a function of the ITD (see METHODS) at selected frequencies across its responsive range. At each frequency, peak-type neurons were maximally excited at about the same ITD (A and B, left), whereas trough-type neurons were minimally excited (C and D, left). In these figures, contralateral and ipsilateral delays are positive and negative, respectively.
The tendency of each neuron to be maximally or minimally excited at the same ITD was quantified by measuring its "characteristic phase" (CP). The CP was obtained from a plot of the mean interaural phase of the response versus the frequency (see METHODS; Fig. 1, right). The CP is the intercept of the fitted line with the ordinate (Yin and Kuwada 1983b
). A CP near 0 cycles (Fig. 1, A and B) indicated that the neuron was of the peak type, whereas a CP of 0.5 cycles (Fig. 1, C and D) indicated that it was of the trough type. The slope of the linear fit yielded a quantitative measure of the neuron's "characteristic delay" (CD, arrowheads in Fig. 1, left) (Rose et al. 1966
; Yin and Kuwada 1983b
), which is a measure of the ITD at which the signals from the two sides arrive in coincidence.
Neurons in the SOC that were sensitive to ITDs in the envelopes of high-frequency sounds could also exhibit peak-type or trough-type sensitivity (Fig. 2). As with neurons sensitive to ITDs of low frequencies (Fig. 1), high-frequency peak-type neurons had CPs near 0 cycles (Fig. 2A and B, right) and trough-type neurons had CPs near 0.5 cycles (Fig. 2C and D, right).

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| FIG. 2.
Sensitivity of 4 neurons in the SOC to ITDs of high-frequency sinusoidally amplitude-modulated (SAM) tones. Format is the same as for Fig. 1, except that delay curves (left) are at different modulation frequencies and phase plots (right) are a function of modulation frequency. The neurons of A and B exhibited peak-type sensitivity to ITDs, whereas the neurons of C and D exhibited trough-type sensitivity. Neurons in A and B were broadly tuned; those in C and D were tested at their best frequencies. Contralateral/ipsilateral intensities (dB SPL): 51/52 (A); 41/42 (B); 40/19 (C); 32/36 (D). Modulation depth: 80% in all cases. Carrier frequencies as indicated.
|
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Distribution of CP and linearity of the phase plots
To assess how well ITD-sensitive units in the SOC could be divided into peak-type and trough-type categories, we examined the distribution of the CP. The CP is well defined only when the phase plot for the unit is linear. Most low-frequency units (91 of 100) and all high-frequency units (25 of 25) met the linearity criterion of Yin and Kuwada (1983b)
. As mentioned, peak-type units should have CPs near 0 cycles, and trough-type units should have CPs near 0.5 cycles, so a strict division into these types should yield a distribution across all units consisting of tight clusters at 0 and 0.5 cycles.
The distribution of CP for units that met the Yin and Kuwada criterion is shown in Fig. 3. For units sensitive to ITDs of low frequencies (filled bars), there were two peaks, one near 0 cycles, corresponding to peak-type units, and the other near 0.5 cycles, corresponding to trough-type units. A similar pattern was present for units sensitive to ITDs of high-frequency SAM tones (open bars). However, in both cases, the CPs were not tightly clustered around 0 and 0.5 cycles, although the clustering was tighter for high-frequency units. It therefore appears that although units in the SOC did tend to be either of the peak type or trough type, the responses of some were irregular.

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| FIG. 3.
Distribution of the CP. For each neuron, the responses at the stimulus parameters that produced ITD sensitivity over the widest range of frequencies in octaves were used. Filled bars: distribution of CP for units sensitive to ITDs in the fine structure of low-frequency tones (n = 91). Open bars: distribution of CP for units sensitive to ITDs in high-frequency SAM tones (n = 25). Dashed line: CP = 0.25 cycles, midway between the ideal value for peak-type units (0 cycles) and that for trough-type units (0.5 cycles).
|
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Examples of low-frequency units with CPs far from 0 or 0.5 cycles are shown in Fig. 4, A and B. These units had delay curves that did not align at either the peak or the trough, but rather at some intermediate point (arrowheads).

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| FIG. 4.
Sensitivity to ITDs of 4 neurons with irregular responses. Format as Fig. 1. All neurons were sensitive to ITDs of low-frequency tones. A and B: 2 neurons with delay curves that had the same relative amplitude at a common ITD; but this amplitude was intermediate between the minimum and the maximum. These neurons had CPs that were far from 0 or 0.5 cycles. C and D: 2 neurons with delay curves that did not align well at any relative amplitude. These neurons had nonlinear phase plots. Best binaural-beat frequencies and average intensity levels (dB SPL): 600 Hz, 77/70 (A); 875 Hz, 64/63 (B); 275 Hz, 63/63 (C); 800 Hz, 63/64 (D).
|
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Other units displayed a different type of irregularity. The phase plots of these units were only loosely fit by a straight line, even though they met the linearity criterion of Yin and Kuwada (see METHODS). Examples of two low-frequency units with phase plots of this type are shown in Fig. 4, C and D. These phase plots appeared to show systematic patterns of deviations, which would not be detected by the criterion of Yin and Kuwada.
In order to investigate whether the deviations from linearity were systematic or random, we performed a runs test (see METHODS). Roughly 40% of the units examined had phase plots with a systematic pattern of deviations (8 of 23 low-frequency, 6 of 13 high-frequency). Systematic deviations were present in both single neurons (10 of 23) and multiple units (4 of 13).
Sometimes these systematic deviations were small, and the line appeared to fit the phases well. For example, the phase plots of the neurons of Figs. 1A and 2, B and D, all had systematic deviations according to the runs test but were fit well with a straight line. Such small, systematic deviations were typical of high-frequency units. At other times the deviations were large (e.g., Fig. 4, C and D), and consequently the phase plots were not fit well by a straight line. Furthermore, units with CPs far from 0 or 0.5 cycles could have linear phase plots (e.g., Fig. 4, A and B). Thus there was a continuum of the magnitude of the deviations from linearity as well as a continuum of linear phase plots with different CPs.
Contralateral and ipsilateral influences
The influences of contralateral and ipsilateral stimulation on the responses of each unit were classified (see METHODS) as excitatory (E), inhibitory (I), absent (0), or complex (C). The complex category consisted of transient excitation followed by sustained inhibition. The response of each unit was represented by a contralateral-ipsilateral pair, e.g., IE.
Low-frequency peak-type units were typically EE or 0E. For example, the neuron of Fig. 1A was EE (Fig. 5A), whereas the neuron of Fig. 1B was 0E (Fig. 5B). The discharge of peak-type neurons was typically synchronized (i.e., phase locked) to the frequency of the tone, as evidenced by multiple peaks in the peristimulus time histograms (PSTs) at intervals equal to the period of the tone (see Fig. 5, insets).

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| FIG. 5.
Responses of low-frequency peak-type and trough-type neurons to monaural stimulation. A and B: same 2 peak-type neurons as in Fig. 1, A and B. C and D: same 2 trough-type neurons as in Fig. 1, C and D. Insets: 1st 20 ms of the response, to demonstrate synchrony to the stimulation frequency. Tick marks above insets are at intervals corresponding to the stimulus period. Frequencies (Hz), intensities (dB SPL), and number of repetitions: 850, 66/74, 100 (A); 600, 51/53, 50 (B); 400, 60/63, 50 (C); 350, 60/63, 75 (D). All stimuli were 50 ms long, presented every 125 ms. Binwidth: 200 µs.
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Low-frequency trough-type units generally responded strongly to ipsilateral stimulation but not at all or only weakly to contralateral stimulation. For example, the neurons of Fig. 1, C and D, both responded strongly to ipsilateral stimulation (Fig. 5, C and D, right), but the former was unresponsive to contralateral stimulation whereas the latter responded weakly (Fig. 5, C and D, left). As with low-frequency peak-type units, excitatory responses were usually synchronized to the period of the tone.
Our sample of high-frequency peak-type units was small, but these units did tend to respond to monaural stimulation with at least partial excitation. The neurons of Fig. 2, A and B, were both excited by contralateral and ipsilateral stimulation (Fig. 6, A and B). However, inhibitory input from the contralateral side was also unexpectedly present in these neurons, as evidenced by a sustained discharge level that was lower than the spontaneous activity (Fig. 6, insets). Such neurons were classified as CE.
High-frequency trough-type neurons were mostly IE. The neurons of Fig. 2, C and D, responded to ipsilateral stimulation with a sustained discharge (Fig. 6, C and D, right). In some neurons, the excitatory response to ipsilateral stimulation showed a sequence of evenly spaced peaks near the onset of the response (Fig. 6C, right, inset), i.e., a transient chopping pattern (e.g., Blackburn and Sachs 1989
; Bourk 1976
; Tsuchitani 1982
; Young et al. 1988
).2 In other neurons there was a brief pause after the first action potential, followed by sustained activity (Fig. 6D, right, inset). This pattern has been referred to as primary-like with notch or OL (e.g., Blackburn and Sachs 1989
; Godfrey et al. 1975
; Smith et al. 1991
). The contralateral inhibitory input was evidenced by suppression of the spontaneous activity (Fig. 6C, left) or by suppression of the discharge elicited by an ongoing ipsilateral tone (Fig. 6D, left).
The monaural properties of low- and high-frequency units falling into the most common categories are summarized in Fig. 7, A and B, where they are presented as a function of CP. Circles denote individual units; ovals denote groups of four units.

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| FIG. 7.
CPs of units in different binaural categories. Binaural category of a unit was usually determined from the responses at the intensity at which ITD sensitivity was tested. If responses at that intensity were unavailable, then responses at the nearest higher intensity were used. A: low-frequency units (n = 55). An I0, an IE, and an 0I unit were not plotted. The IE unit was a multiunit recording of the trough type. Of the 11 units with CPs nearer 0.5 cycles than 0 cycles that were classified as 0E, 7 had sufficient spontaneous activity to have permitted detection of contralateral inhibition. B: high-frequency units (n = 25). An EI and an II unit were not plotted. 0E units were tested with monaural stimuli. Circles: individual units. Ovals: groups of 4 units with CPs within 0.1 cycles.
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For low-frequency units (Fig. 7A), the most common categories were EE, 0E, E0, and 00. Inhibition from either side was rarely observed (3 units, not plotted). Most low-frequency peak-type units (CPs near 0 cycles) were 0E or EE. Both these categories were consistent with a bilateral excitatory input, if an 0 response represents subthreshold excitation in peak-type units. Most low-frequency trough-type units were 0E, which was consistent with a simple IE mechanism, if in these units the 0 response reflects an inhibitory input. There were also some EE trough-type units, which is not entirely consistent with a simple IE mechanism, although the excitatory contralateral response could represent a cycle-by-cycle rebound from inhibition (Finlayson and Caspary 1991
). It was surprising that contralateral inhibition was not directly observed in low-frequency trough-type units either as an OFF response or as suppression of the spontaneous activity that was often present. Units with irregular responses (CPs far from 0 and 0.5 cycles) were distributed across the four most common categories. This can be seen by observing that CPs of units in these categories were not tightly clustered around 0 or 0.5 cycles.
Most high-frequency peak-type units fell into categories compatible with a bilateral excitatory input (Fig. 7B), although two did receive contralateral inhibition as well. The responses of most high-frequency trough-type units were compatible with the presence of contralateral inhibition and ipsilateral excitation.
The encoded ITD
Neurons in the SOC presumably encode ITDs that are then transmitted to higher levels. The encoded ITD for a given neuron may be reflected in its composite delay curve or in its CD. The composite delay curve of a unit is obtained by averaging its response as a function of ITD across frequencies (Kuwada et al. 1987
; Yin and Kuwada 1983b
). For a low-frequency neuron, the composite delay curve has a similar form to the response of the neuron to interaurally delayed noise (Yin and Chan 1990
; Yin et al. 1986
). For a high-frequency neuron, the composite delay curve is similar to the response to interaural delays of a band of noise centered at the neuron's characteristic frequency (Joris and Yin 1995
).
Examples of composite delay curves of low-frequency neurons are shown in Fig. 8. Peak-type neurons (Fig. 8, A and B) had a central peak, whereas trough-type neurons had a central trough (Fig. 8, C and D). Neurons with irregular responses (Fig. 8, E-H) also had peaks or troughs in their composite delay curves that could be used to encode the ITD of a broadband sound. This indicates that the irregularities that occur in the phase plots are such that ITD sensitivity to broadband sounds is preserved.

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| FIG. 8.
Composite delay curves of selected low-frequency neurons. A-D: the 2 peak-type and 2 trough-type neurons of Fig. 1. E-H: the 4 neurons of Fig. 4 with irregular responses. Composite delay curves were based on delay curves that had 10 bins/cycle. In the ±1.5-ms interval, 300 points were interpolated.
|
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The composite delay curves of high-frequency peak- and trough-type neurons (Fig. 9) were similar to their low-frequency counterparts in that the peak-type neurons had a central peak and the trough-type neurons had a central trough. However, the widths of the peaks and the troughs were at least twice as broad as those of their low-frequency counterparts.

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| FIG. 9.
Composite delay curves of selected high-frequency neurons. The 2 peak-type and two trough-type neurons of Fig. 2 are illustrated. Composite delay curves were based on delay curves that had 10 bins/cycle. In the ±6-ms interval, 300 points were interpolated.
|
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The composite delay curves of units with irregular responses formed a continuum with those of peak- and trough-type units. Irregular units with CPs closer to 0 cycles had composite delay curves that resembled those of peak-type units, whereas irregular units with CPs closer to 0.5 cycles had composite delay curves that resembled those of trough-type units. For this reason, each unit was broadly classified as either peak type or trough type on the basis of whether its CP was nearer 0 or 0.5 cycles (Fig. 3, dashed line).
In Fig. 10 we compare the distributions of the the CD (A and B), the composite peak delay (C), and the composite trough delay (D) for peak- and trough-type units (for calculation of composite peak and trough delay see legend to Fig. 10). Filled and open bars refer to units sensitive to ITDs of low-frequency sounds and to envelopes of high-frequency sounds, respectively.

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| FIG. 10.
Distributions of CD and composite peak and trough delay. Filled bars: low-frequency units. Open bars: high-frequency units. A: distribution of CD for peak-type units (low-frequency, n = 52; high-frequency, n = 6). B: distribution of CD for trough-type units (low-frequency, n = 39; high-frequency, n = 19). C: distribution of composite peak delay for peak-type units. D: distribution of composite trough delay for trough-type units. Number of units in C and D is the same as in A and B. Composite peak and trough delays were calculated from composite delay curves constructed over a ±4-ms interval by fitting a parabola to the upper 30% of the peak of the composite delay curve (Kuwada et al. 1987 ) and the lower 30% of the trough of the composite delay curve. Number of units outside plotted range (low-frequency, high-frequency): 1, 1 (A); 1, 3 (B); 5, 1 (C); 1, 1 (D).
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The CDs of almost all low-frequency peak- and trough-type units (Fig. 10, A and B) lay within the range of delays that a rabbit would likely encounter in the free field (~80% for both types; ±300 µs) (Heffner and Masterton 1980
). However, the two types of units had CDs associated with sounds arising in different hemifields. Almost all peak-type units (42 of 52, 81%) had CDs corresponding to the contralateral hemifield (ipsilateral delays). In contrast, the CDs of low-frequency trough-type units were biased (24 of 39, 62%) toward the ipsilateral hemifield (contralateral delays).
High-frequency trough-type units had CDs that were biased in the same direction as those of their low-frequency counterparts (13 of 19, 68%), but fewer lay in the free-field range (10 of 19, 53%). Our sample of high-frequency peak-type units was too small for meaningful comparisons.
In general, the distribution of composite peak delays (Fig. 10C) of the peak-type units was similar to the distribution of their CDs (Fig. 10A), albeit somewhat broader. The distribution of composite trough delays (Fig. 10D) of the trough-type units was similar to the distribution of their CDs (Fig. 10B).
The composite delay curves of low-frequency units had both a peak and a trough, so it could be argued that one is as important as the other for all units. Therefore we also measured the composite trough delay of peak-type units and the composite peak delay of trough-type units. In both cases, almost all these values fell outside the free-field range of the rabbit (45 of 52 for peak-type units; 36 of 39 for trough-type units). High-frequency units had only a peak or a trough, but not both, within the window used to calculate the composite delay curve.
Location of peak-type and trough-type units
Our method for locating individual units was subject to considerable error. First, recordings were made over months, and then locations of all recording sites were reconstructed relative to one or a few lesions made at the end of this period (see METHODS). Second, the distance between the entry point and the SOC was large (~15 mm), so any deviation in the straightness of the electrode or in the hypodermic guide would lead to error in placement. For example, a mere 2° deviation in straightness could lead to a ~500-µm error, roughly the width of the MSO in the rabbit.
As before, units were divided into two broad categories on the basis of their CPs, namely peak type and trough type. This appeared justified because a pooled reconstruction of recording sites indicated that units with irregular responses were scattered in and around the MSO and LSO, intermingled with other units, and not restricted to any one region.
Despite the limitations in our methods for localizing units and in classifying them, the locations of the recording sites were generally consistent with the notion that peak-type units were associated with the MSO and trough-type units were associated with the LSO. Drawings of two penetrations in which lesions were made are shown in Fig. 11, A and B. In Fig. 11A, the middle lesion of the three lies just medial to MSO. All low-frequency units studied on this side of the brain were of the peak type (6 of 6), and most lay within 500 µm of the lesion. In Fig. 11B, the deepest of three lesions is just ventral to LSO, and the lesions extend through the lateral limb. Almost all of the low-frequency units studied in this animal were of the trough type (6 of 7) and lay within 500 µm of the lateral limb.

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| FIG. 11.
Location of recording sites. A: locations of lesions in a case for which units studied in the vicinity of the lesion were of the peak type. The middle of 3 lesions is just medial to the medial superior olive (MSO). In this animal, recordings were made from both sides. Medial limb of the lateral superior olive (LSO) on side opposite lesions is obscured by electrode tracks. LTB, lateral nucleus of trapezoid body; MTB, medial nucleus of trapezoid body; VTB, nucleus of ventral trapezoid body; Pyr, pyramid; Tz, trapezoid body. B: locations of lesions in a case for which most units studied were of the trough type. In this case, ITD sensitivity was encountered ~700 µm dorsal to the most ventral of 3 closely spaced lesions, in the region of the lateral limb of LSO. Note that the LSO of the rabbit has 4 limbs and is M shaped. C: reconstruction of recording sites for peak-type units. One animal (88S09) was excluded because of a large scatter in the reconstructed sites, perhaps because of the loss of a needed reference mark on the skull. , low-frequency units (n = 43); , high-frequency units (n = 5). D: similar reconstruction for trough-type units (low-frequency, n = 36; high-frequency, n = 17).
|
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A reconstruction of recording sites pooled across animals is shown in Fig. 11, C and D. The location of each unit was determined relative to a lesion made at the end of recordings in that animal, and the mediolateral and dorsoventral location of the lesion were determined relative to the MSO. All locations were then plotted on a common section, so that the rostrocaudal dimension was compressed. Low- and high-frequency peak-type units (Fig. 11C,
and
) tended to lie in the vicinity of the MSO, with a smaller grouping near the medial limbs of LSO. In contrast, low-frequency trough-type units (Fig. 11D,
) tended to lie laterally and dorsally, in the vicinity of the lateral limb, or low-frequency region, of the LSO. High-frequency trough-type units (
) were located in or near the medial, high-frequency part of LSO.
Further evidence that peak-type and trough-type units were segregated came from penetrations in which we recorded more than one unit. All units in such penetrations tended to be of one type (23 of 28 penetrations).
 |
DISCUSSION |
We have shown that, as in the IC, there are peak-type and trough-type neurons in the SOC. However, we have also shown that many neurons have irregular responses. We discuss the possible reason for the presence of cells with these irregular responses, followed by discussions of low- and high-frequency peak-type and trough-type units in the SOC and the relationship between ITD sensitivity in the SOC and in the IC.
Irregular responses
We defined units as having irregular responses if they had phase plots that deviated systematically from linearity or had intercepts (CPs) far from 0 or 0.5 cycles. It is conceivable that irregular responses were caused by erroneous acoustic calibrations resulting from day-to-day variations in the position of the ear molds. This seems unlikely, at least for low-frequency units. Repeated measurements of the calibrations indicated that any existing pattern of irregularities in the interaural phase differences at these frequencies was maintained after the ear molds were removed and reinserted. Furthermore, irregular responses were observed in the same animals as units that were not irregular, and different units from a particular animal could have different patterns of irregularities. At high frequencies, however, the variability in the interaural phase calibrations was greater. This variability precluded phase corrections, and it is possible that the small, systematic deviations from linearity that were observed in high-frequency units reflected irregularities in the acoustic calibrations.
Another possible artifactual source of irregular responses was the multiunit recordings. However, a somewhat greater fraction of single than multiple units had phase plots that deviated systematically from linearity, as demonstrated by the runs test. Also, both single and multiple units could have CPs far from 0 or 0.5 cycles.
Units with irregular responses did not appear to form a separate population within the SOC either physiologically or anatomically. First, the CP distribution formed a continuum, with no clear demarcation of these units. Second, there was no clear delineation in terms of the degree of nonlinearity as gauged by the MSE of the linear fit to the phase plot (Yin and Kuwada 1983b
). Third, units with irregular responses did not differ from other units in the distribution of their CDs or in the positions of their composite peaks or troughs. Finally, they did not appear to lie in locations distinct from those of other units.
Units with irregular responses also did not specifically appear to have characteristics that have previously been related to those of neurons in periolivary nuclei. Spitzer and Semple (1995)
found that ITD-sensitive neurons were present in a dorsal-rostral-medial region of the SOC of the gerbil. These neurons typically did not phase lock, and they were monaurally unresponsive, i.e., they did not respond to stimulation of one or both ears individually (E0, 0E, and 00 units). However, in the present study there was no clear association between monaurally unresponsive units and units with irregular responses, suggesting that irregularities were not specific to neurons in periolivary nuclei. Further evidence that irregular responses were not specifically associated withperiolivary neurons is provided in the companion paper (Batra et al. 1997
), in which the phase locking of neurons in the SOC is examined. For these reasons we consider units with irregular responses to be variants of peak- and trough-type units rather than a distinct population. Thus it seems likely that the MSO and LSO both contain neurons with irregular responses.
There is evidence for irregular responses in other studies of the SOC. Moushegian et al. (1971)
reported a neuron in the kangaroo rat with delay curves at different frequencies that did not coincide "...either at the peak, valley or at any other point." This description is consistent with the nonlinear phase plots associated with some irregular responses. Two other studies of the MSO reported irregular responses (Spitzer and Semple 1995
; Yin and Chan 1990
), although they did not draw specific attention to them. The phase plot shown by Yin and Chan (1990)
, and one of the two shown by Spitzer and Semple (1995)
, show oscillations. In addition, the distributions of CP in both studies were not tightly clustered about 0 cycles. The spread of the CP distribution in the gerbil (Spitzer and Semple 1995
) was wider than that in the cat (Yin and Chan 1990
) and about as wide as we observed for peak-type units in the rabbit.
The presence of systematic deviations from linearity in phase plots, as well as the existence of neurons with CPs far from 0 or 0.5 cycles, is incompatible with the simple convergence of bilateral excitatory inputs or the convergence of an excitatory input from one side with an inhibitory input from the other. A CP far from 0 or 0.5 cycles could be created by a frequency-independent phase shift in one input, but there is no clear way that such a phase shift could be neurally generated. However, both types of irregularities could be the result of additional phase-locked inputs into the binaural cell. To examine this possibility, we constructed a model that had three phase-locked inputs: an ipsilateral excitatory input, a contralateral excitatory input, and a contralateral inhibitory input (Fig. 12A). This model represents either an MSO neuron with an additional inhibitory input or an LSO neuron with an additional excitatory input. Each input was represented by a single sinusoid at the stimulation frequency (f). The amplitude of each input could vary independently, and the two contralateral inputs could be neurally delayed relative to the ipsilateral input (
e and
i). An external interaural phase difference could also be imposed (
). The response amplitude of the binaural cell was the amplitude of the summed inputs. By varying the external interaural phase difference, we could calculate the mean interaural phase of the response.

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| FIG. 12.
A possible model for irregular responses. A: schematic of the model. Binaural cell ( ) receives 3 inputs: an ipsilateral excitatory input (Ei), a contralateral excitatory input (Ec), and a contralateral inhibitory input (Ic). Model represents either a neuron in the MSO with an additional contralateral inhibitory input or a neuron in the LSO with an additional contralateral excitatory input. Inputs were modeled by sine waves at the stimulus frequency (f) with individual amplitudes. The contralateral inputs were delayed ( e, i) or advanced relative to the ipsilateral input. An external interaural phase difference ( ) could be introduced. Response amplitude |R| was equal to the amplitude of the summed inputs. B-D: model was used to generate phase plots such as those in Fig. 4. Ai dropped out of the final equations for these plots. Values of the 3 free parameters Aci/Ace, e, and i (ms): 0.8, 0.3, 0.3 (B); 2.0, 1.9, 1.9 (C); 1.4, 0.9, 0.2 (D).
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We found that this model could reproduce several features of phase plots recorded in the SOC. Elimination of the inhibitory input resulted in a linear phase plot with a CP of 0 cycles, whereas elimination of the contralateral excitatory input resulted in a linear phase plot with a CP of 0.5 cycles. In contrast, presence of all three inputs led to more complex phase plots. Over the frequency range in which units in the SOC normally responded to ITDs, suitable choices of parameters could produce linear phase plots with intercepts far from 0 or 0.5 cycles (Fig. 12B), sharp jumps in the mean interaural phase (Fig. 12C), or curvature of the phase plot (Fig. 12D). For such complex phase plots, the differences between the delays of the various inputs could be greater than the CD (as calculated from the slope of the fit) and not related in any simple way to it. Thus it is possible that systematic deviations from linearity in phase plots and the existence of units with CPs far from 0 or 0.5 cycles could be due to one or more additional phase-locked inputs to the binaural neurons of the SOC.
The MSO does, in fact, receive both ipsilateral and contralateral inhibition (Grothe and Sanes 1993
, 1994
; Smith 1995
) in addition to bilateral excitatory input. Ipsilateral inhibitory input is likely to come via the lateral nucleus of the trapezoid body (Cant and Hyson 1992
; Kuwabara and Zook 1992
) and contralateral inhibitory input via the medial nucleus of the trapezoid body (Banks and Smith 1992
; Cant and Hyson 1992
; Covey et al. 1991
; Kiss and Majorossy 1983
; Kuwabara and Zook 1992
; Spangler et al. 1985
). The inhibitory input from both these nuclei is likely to be phase locked because they receive input from globular bushy cells of the anteroventral cochlear nucleus (Kuwabara et al. 1991
; Smith et al. 1991
; Tolbert et al. 1982
; Warr 1972
, 1982
), which synchronize strongly to tones (Smith et al. 1991
). Parts of the MSO may also receive multiple excitatory inputs from the contralateral side with differing delays (Oliver and Beckius 1996
), which could contribute to the presence of irregular responses as well.
The LSO also receives inputs in addition to the contralateral inhibition that comes via the medial nucleus of the trapezoid body and the ipsilateral excitation that comes from the spherical bushy cells of the anteroventral cochlear nucleus. There appears to be a projection from the contralateral cochlear nucleus that is probably excitatory (Glendenning et al. 1985
; Goldberg and Brown 1968
; Kil et al. 1995
; Warr 1982
), although its extent varies among species. There are also other ipsilateral inputs from the lateral nucleus of the trapezoid body (Kuwabara and Zook 1992
) and from a region of the cochlear nucleus that does not contain spherical bushy cells (Cant and Casseday 1986
).
There is another factor that may also act to generate irregular phase plots in the SOC. The phase of response of auditory nerve fibers to tones is known to vary nonlinearly with frequency (Pfeiffer and Molnar 1970
). Nonlinearities in the interaural phase plots of neurons in the SOC could result if the nonlinearities of the inputs from the two sides (or even 2 inputs from the same side) were mismatched, as might occur if the best frequencies of the two inputs differed slightly. It is unlikely that the "peak splitting" observed in auditory nerve fibers (e.g., Ruggero and Rich 1989
) contributes to the nonlinearities, because this effect occurs only at high intensities not employed here.
The underlying mechanisms that give rise to units with irregular responses may differ somewhat from those that give rise to peak-type and trough-type units. However, units with irregular responses still have composite delay curves that are modulated with ITD, and so these units may function to encode ITDs to broadband sounds in much the same way that peak- and trough-type units do. The function of irregularities may be to shift the ITD sensitivity of a neuron without requiring changes in the anatomic delays of its inputs. Such flexibility may be important in adjusting the system to changes in, for example, head size.
Low-frequency peak-type units
Most low-frequency peak-type units in the rabbit were localized to the vicinity of the MSO. This location is consistent with other reports that units near or in MSO have CPs near 0 cycles (Spitzer and Semple 1995
; Yin and Chan 1990
). Other peak-type units were localized to the vicinity of the LSO. This may be an error in localization. However, neurons with peak-type characteristics have been reported in the hilus of the LSO of the gerbil (Spitzer and Semple 1995
). It is also possible that some of these units may have been high-frequency units that were studied in the tails of their tuning curves.
The monaural responses of low-frequency peak-type units were primarily EE and 0E, which is in accord with the presence of an excitatory input from either side, if the absence of a response is construed as subthreshold excitation. These response types are also in accord with previous studies (Spitzer and Semple 1995
; Yin and Chan 1990
) and with the main excitatory afferents to MSO.
Most peak-type neurons in the rabbit favored ipsilateral delays, which would be produced by sounds in the contralateral sound field. This agrees with studies in other species that have also measured CDs or composite peak delays in the MSO (cat: Yin and Chan 1990
; gerbil: Spitzer and Semple 1995
). Other studies have used the ITD at which maximal discharge occurs as a measure of the encoded ITD. Crow et al. (1978)
found a nearly even distribution of the best delay between the sound fields in the MSO of the kangaroo rat, with a slight bias toward ipsilateral delays. The preference for ipsilateral delays presumably reflects a shorter path length from the ipsilateral side compared with the contralateral side. Langford (1984)
, by contrast, found that most neurons in the MSO of the chinchilla preferred contralateral delays.
The CDs and composite peak delays of most units in the rabbit lay within about ±300 µs, as they also did in other species that have been examined (kangaroo rat: Crow et al. 1978
; chinchilla: Langford 1984
; gerbil: Spitzer and Semple 1995
; cat: Yin and Chan 1990
). This is a consistent feature despite the fact that some of these species have small heads, which should limit the ITDs available. For example, the ITD available to a gerbil in the free field should be <100 µs. Palmer et al. (1990)
made a similar observation for the ITDs encoded in the ICs of different species.
Neurons sensitive to large ITDs may still encode ITDs in the free-field range, because most of these neurons do have differential sensitivity to ITDs within this range even though their peak sensitivity lies outside of it. Unlike in the IC of the guinea pig (McAlpine et al. 1996
), neurons with large CDs were not necessarily of low best frequency as measured with the use of the binaural-beat stimulus.
Low-frequency trough-type units
Most of our low-frequency trough-type units were localized to the vicinity of the lateral limb of the LSO. Reports of such neurons are few. There are doubtless many reasons for this. Jeffress' (1948) early model for generating a sensitivity to ITDs produced peak-type units and required bilateral excitatory input, which matched the anatomy of the MSO (Jeffress 1958
). Many investigators may therefore have focused their attention on the MSO. The mechanism for trough-type sensitivity to ITDs was not explored until much later (Batra et al. 1993
; Joris 1996
; Kuwada et al. 1987
; Rose et al. 1966
; Yin and Kuwada 1983b
).
A few other reports of sensitivity to ITDs of low-frequency sounds in the LSO have appeared (Caird and Klinke 1983
; Finlayson and Caspary 1991
; Joris and Yin 1995
; Spitzer and Semple 1995
). Caird and Klinke (1983)
and Joris and Yin (1995)
each reported the responses of one neuron tested at one frequency. These responses were IE, and therefore consistent with a trough-type mechanism. Finlayson and Caspary (1991)
demonstrated ITD sensitivity in a large sample of neurons in the lateral limb that were also IE. In contrast to the present results, Finlayson and Caspary found that these neurons discharged more strongly at zero ITD than at the large ITDs produced by 180°-out-of-phase stimulation. The reason for this difference is unclear.
In the gerbil, Spitzer and Semple (1995)
found no trough-type neurons in the LSO, despite a specific search for them. They found only a few neurons near the medial edge of the lateral limb that were ITD sensitive. In contrast to our results, the responses of these neurons were more consistent with a peak-type mechanism. Spitzer and Semple attributed the presence of peak-type sensitivity in the LSO to a direct input from the contralateral cochlear nucleus that is probably excitatory (Kil et al. 1995
). Although this input appears to be present in a number of species, it is exceptionally large in the gerbil.
Somewhat surprisingly, we saw almost no examples of inhibition to contralateral stimulation alone in low-frequency trough-type units. Instead, most units either did not respond or responded with excitation to a contralateral stimulus. This excitatory response was frequently associated with units that had responses that were irregular to varying degrees. One exception was a clear example of a trough-type unit (Fig. 1D) for which the contralateral excitatory response was present but small (Fig. 5D). In this case, it may have reflected a cycle-by-cycle rebound from inhibition. The absence of a response to contralateral stimulation in most ITD-sensitive neurons of low-frequency LSO has been previously noted (Finlayson and Caspary 1991
).
In contrast to peak-type units, trough-type units had CDs that were biased toward contralateral delays. This bias presumably reflects a shorter conduction time from the contralateral side. In high-frequency neurons of LSO, the ability of the contralateral input to precede the ipsilateral input has been noted by Tsuchitani (1988)
.
The LSO has traditionally been considered a center for coding interaural intensity differences. However, at low frequencies the head does not cast a significant sound shadow, and interaural intensity differences are small. Thus under free-field conditions the responses of low-frequency trough-type neurons are likely modulated more by ITDs than by interaural intensity differences. Traditionally, ITDs have been thought to be encoded by the maximal discharge of a neuron. However, there is no a priori reason why trough-type neurons cannot encode ITDs in the free-field range by discharging minimally.
Another possible role for trough-type neurons is encoding information about reverberant environments, e.g., spaciousness. The presence of reflections results in a decorrelation of the sounds reaching the two ears. Neurons in the LSO would respond to such decorrelation with an increased discharge, because the arrival of the contralateral inhibitory input would not be synchronized with that of the ipsilateral excitatory input. Such an increased discharge is, in fact, observed in high-frequency neurons of the LSO when the envelopes of noise presented to the two ears are decorrelated by introducing long delays (Joris and Yin 1995
).
Yet another role for trough-type neurons may be to sharpen ITD tuning in the IC. Low-frequency neurons in the IC do have narrower delay curves than their counterparts in the SOC (Fitzpatrick et al. 1997
). We have already suggested that high-frequency trough-type neurons in the IC may sharpen the azimuthal receptive fields of peak-type neurons via lateral inhibition (Batra et al. 1993
). Low-frequency trough-type neurons in the SOC could sharpen the receptive fields of peak-type neurons in the IC by feedforward inhibition (Kuwada et al. 1997
). Some neurons of the LSO are presumed to be inhibitory, and these project directly to the ipsilateral IC (Glendenning et al. 1992
; Saint Marie and Baker 1990
; Saint Marie et al. 1989
). Others are presumed to be excitatory, and feedforward inhibition could arise indirectly from these via the dorsal nucleus of the lateral lemniscus.
High-frequency peak-type units
Most of the few high-frequency peak-type neurons were located near or in the ventral portion of the MSO, as was the one neuron encountered by Yin and Chan (1990)
in the cat. This is the part of the MSO that is believed to be sensitive to high frequencies (Goldberg and Brown 1968
; Guinan et al. 1972b
).
The CDs of most high-frequency peak-type units were within the free-field range of the rabbit, but our sample was too small to determine whether there was a bias toward ipsilateral or contralateral delays. The composite curves were usually very broad, and little modulation of the curve could be discerned within the free-field range. The broad curves were a consequence of the range of modulation frequencies to which these neurons were sensitive. This range extended lower and did not go as high as the range of frequencies to which low-frequency neurons were sensitive. The few peak-type neurons encountered by Joris (1996)
in the MSO of the cat had similar properties.
High-frequency trough-type units
High-frequency trough-type units were located in the vicinity of the medial (high-frequency) limb of LSO. Neurons with similar properties have also been reported in the LSO of the cat (Joris 1996
; Joris and Yin 1995
).
Our high-frequency trough-type units had properties consistent with those of typical LSO neurons. Most were excited by ipsilateral stimulation and suppressed by contralateral stimulation, as described by others (e.g., Boudreau and Tsuchitani 1968
; Caird and Klinke 1983
; Finlayson and Caspary 1989
; Guinan et al. 1972a
,b
; Moore and Caspary 1983
; Sanes 1990
; Wu and Kelly 1991
). In two neurons, both excitatory and inhibitory inputs were observed to ipsilateral stimulation. The PSTs to ipsilateral stimulation were typically of the transient chopper type (3 of 13) or of the primary-like with notch or OL type (6 of 13). Both types are consistent with earlier reports (Boudreau and Tsuchitani 1970
; Brownell et al. 1979
; Guinan et al. 1972a
,b
; Tsuchitani 1982
), although we encountered a larger fraction of units with primary-like-with notch or OL PSTs. These latter PST types may be more characteristic of the unanesthetized LSO (Brownell et al. 1979
).
High-frequency trough-type units tended to have CDs that favored contralateral delays within the range of ITDs that a rabbit would encounter under free-field conditions. Joris (1996)
recently found that high-frequency units in the LSO of the cat had CDs that favored ipsilateral delays. In that study and ours, the sample size was small (~20 units). However, our distribution for high-frequency units is similar to that for our low-frequency trough-type units, for which we have a larger sample.
The high-frequency trough-type neurons of the LSO may play more than one role in binaural processing. Joris and Yin (1995)
have convincingly argued that the range of interaural intensity differences that an animal normally encounters in the free field will modulate the response of these neurons more than the range of ITDs. Thus a major function of these neurons is presumably to encode interaural intensity differences. However, in addition, these neurons may also play roles similar to those posited for low-frequency trough-type neurons, encoding information about reverberant environments and sharpening the azimuthal receptive fields of peak-type neurons in the IC.
Comparisons with the IC
There were many similarities between the sensitivity to ITDs of neurons in the SOC and in the IC. In both structures, low- and high-frequency peak- and trough-type neurons were present, as were neurons that had responses that were irregular to varying degrees. In what follows we compare the irregular responses in the two centers, the proportions of different neurons, and the ITDs encoded.
IRREGULAR RESPONSES.
In both the SOC and the IC, there were units with nonlinear phase plots and units with CPs that were far from 0 and 0.5 cycles (Batra et al. 1993
; Kuwada et al. 1987
). In the IC we used a
2 test to assess deviations from linearity of phase plots (see METHODS), whereas in the SOC we assessed systematic deviations with the use of the runs test. To provide comparisons with the IC, we also performed the
2 test on the units in the SOC. With the use of this test, a similar proportion of units in the SOC and the IC had nonlinear phase plots [low-frequency: 67% in the SOC vs. 75% in the IC; high-frequency: 80% in the SOC vs. 77% in the IC, (unpublished observations)]. Thus the nonlinearities in the phase plots of neurons in the IC may be inherited, in part, from the responses of neurons in the SOC.
There were, however, some differences in the types of nonlinearities in the two centers. In the IC, many high-frequency neurons had pronounced nonlinearities at low modulation frequencies (250 Hz). In extreme cases, the phase plots consisted of two distinct linear segments with different CDs and CPs. There were also low-frequency neurons in the IC with such "dual CDs" (Stanford 1989
). In the SOC, nonlinearities did not preferentially occur at lower frequencies, and dual CDs were not evident. Consequently, some of the interactions that produce nonlinear phase plots in the IC probably lie at levels above the SOC. These interactions could occur among the projections to the IC from the MSO, LSO, and dorsal nucleus of the lateral lemniscus (reviewed by Oliver and Huerta 1992
), via the intrinsic circuitry of the IC (Oliver et al. 1991
), or via descending connections from the cortex (reviewed by Oliver and Huerta 1992
).
PROPORTIONS OF DIFFERENT NEURONS.
Low- and high-frequency peak- and trough-type neurons are found in the IC, but their proportions appear to differ from those in the SOC. In the IC (Kuwada et al. 1987
; Stanford et al. 1992
) there are fewer low-frequency trough-type neurons than in the SOC. The greater proportion of trough-type neurons in the SOC may be a consequence of the relative frequency with which we penetrated LSO or MSO. However, there is also another possibility. The trough-type neurons in the LSO may be inhibitory and so not produce trough-type responses in the IC. There is evidence that a proportion of neurons in the LSO that project ipsilaterally is inhibitory (Glendenning et al. 1992
; Saint Marie and Baker 1990
; Saint Marie et al. 1989
). If the rabbit follows the pattern in the cat (Glendenning and Masterton 1983
; Saint Marie et al. 1989
), where low-frequency LSO projects primarily ipsilaterally, then the proportion of low-frequency trough-type neurons in IC would be small.
The reverse situation holds for high-frequency peak-type units. We encountered few of these neurons in the SOC, but many in the IC (Batra et al. 1993
). The paucity in the SOC may be due to a sampling bias or may reflect extensive arborization of high-frequency MSO inputs to the IC. Alternatively, the increased number of peak-type neurons in the IC may occur via the complex interaction of multiple sources (Batra et al. 1993
). On this point, many high-frequency peak-type neurons in the IC were inhibited by ipsilateral and excited by contralateral stimulation, which is an unexpected combination of inputs for peak-type responses.
THE ENCODED ITDS.
Most neurons in both the SOC and the IC encoded ITDs within the free-field range of the rabbit (Batra et al. 1993
; Kuwada et al. 1987
; Stanford et al. 1992
), a feature that is also preserved at the level of the thalamus (Stanford et al. 1992
). Peak-type units in both the SOC and the IC tend to prefer ipsilateral delays. Trough-type units, however, have CDs and composite trough delays biased toward contralateral delays in the SOC, but in the IC show a shift toward ipsilateral delays (low frequency: personal observations; high-frequency: Batra et al. 1993
). This shift may be due to the proportion of the projection from LSO that is crossed (reviewed by Oliver and Huerta 1992
). Similarly, high-frequency trough-type units in the IC were mostly EI (Batra et al. 1993
), whereas in the SOC they were nearly all IE. This reversal in laterality may also reflect the crossed projection from the LSO to the IC.