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The Journal of Neuroscience, December 1, 1998, 18(23):10157-10170
Temporal and Binaural Properties in Dorsal Cochlear Nucleus and
Its Output Tract
Philip X.
Joris1, 2 and
Philip H.
Smith3
1 Division of Neurophysiology, K.U. Leuven,
Medical School, B-3000 Leuven, Belgium, and 2 Department of
Neurophysiology and 3 Department of Anatomy, University of
Wisconsin-Madison, Madison, Wisconsin 53706
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ABSTRACT |
The dorsal cochlear nucleus (DCN) is one of three nuclei at the
terminal zone of the auditory nerve. Axons of its projection neurons
course via the dorsal acoustic stria (DAS) to the inferior colliculus
(IC), where their signals are integrated with inputs from various other
sources. The DCN presumably conveys sensitivity to spectral features,
and it has been hypothesized that it plays a role in sound localization
based on pinna cues. To account for its remarkable spectral properties,
a DCN circuit scheme was developed in which three inputs converge onto
projection neurons: auditory nerve fibers, inhibitory interneurons, and
wide-band inhibitors, which possibly consist of Onset-chopper
(Oc) cells. We studied temporal and binaural
properties in DCN and DAS and examined whether the temporal properties
are consistent with the model circuit.
Interneurons (type II) and projection (types III and IV) neurons
differed from Oc cells by their longer latencies and
temporally nonlinear responses to amplitude-modulated tones. They also
showed evidence of early inhibition to clicks. All projection neurons examined were inhibited by stimulation of the contralateral ear, particularly by broadband noise, and this inhibition also had short
latency. Because Oc cells had short-latency responses and were well driven by broadband stimuli, we propose that they provide short-latency inhibition to DCN for both ipsilateral and contralateral stimuli. These results indicate more complex temporal behavior in DCN
than has previously been emphasized, but they are consistent with the
recently described nonlinear behavior to spectral manipulations and
with the connectivity scheme deduced from such manipulations.
Key words:
audition; dorsal cochlear nucleus; dorsal acoustic stria; amplitude modulation; temporal; binaural; cat
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INTRODUCTION |
The dorsal cochlear nucleus
(DCN) is one of three nuclei at the terminal zone of the auditory
nerve. Axons of its projection cells leave the nucleus via the dorsal
acoustic stria (DAS) and project to the inferior colliculus (IC) (Osen,
1972
; Adams and Warr, 1976; Oliver, 1984). The DCN is the most complex
subdivision of the cochlear nucleus, and its function remains unknown.
Young and colleagues (1992) proposed that the DCN serves a role in the detection of spatial elevation of a sound source by virtue of its
sensitivity to spectral features such as those resulting from the
directionally dependent filtering properties of the pinna.
One strategy for obtaining clues to the function of the DCN is to
examine the effect of its very nonlinear spectral properties (Nelken et
al., 1997) on the IC (Semple and Aitkin, 1980). For example, inputs
from the DCN partly converge with inputs from the lateral superior
olive (LSO) (Oliver et al., 1997). Cells in the LSO are sensitive to
interaural level differences (ILDs) (Boudreau and Tsuchitani, 1968) and
interaural time differences of amplitude-modulated (AM) tones (Joris
and Yin, 1995), which are cues to the azimuthal position of a sound
source. Cells in the IC with spatially restricted receptive fields have
been described (Moore et al., 1984), and an appealing hypothesis is
that such receptive fields would be assembled from DCN and LSO inputs.
We therefore wished to compare DCN with LSO responses in two respects. First, the cochlear nucleus (CN) is usually thought of as a monaural nucleus, but there have been reports of excitatory and inhibitory binaural interactions, particularly in the DCN (Mast, 1970, 1973; Hochfeld, 1973; Young and Brownell, 1976). These need further characterization if effects of the DCN on the IC are to be studied because here binaural and monaural pathways converge. Second, like the
LSO (Tsuchitani and Boudreau, 1966; Guinan et al., 1972), the DCN has a
high-frequency bias (Spirou et al., 1993), and was traditionally viewed
as a structure with little sensitivity in the temporal domain, as
evident in responses to pure tones (Goldberg and Brownell, 1973).
However, recent studies of the DCN with AM stimuli have challenged that
view (Rhode and Greenberg, 1994). We studied responses of DCN neurons
to AM stimuli that were also used in previous LSO studies.
A final reason to further characterize both binaural and temporal
sensitivities in the DCN is preliminary anatomical evidence from
intra-axonal labeling experiments [Joris et al. (1992) and our
unpublished results] that one class of inhibitory neurons, Oc cells in the posteroventral cochlear nucleus
(PVCN) and deep DCN, may have a role in both kinds of
sensitivity, because they project to both ipsilateral and contralateral
DCN. A spectral role for these cells was first suggested by Nelken and
Young (1994). These authors surmised that convergence of three inputs
is needed to explain the spectral properties of DCN output neurons:
auditory nerve fibers, inhibitory (type II) interneurons, and a
wide-band inhibitory source, which they hypothesized to be
Oc cells. Here, we examine whether these proposed
interactions hold up when examined in the time domain.
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MATERIALS AND METHODS |
Data for the present report were derived from 13 DCN-DAS
experiments that also contributed data for a previous publication (Joris, 1998), in which methodological details can be found.
Animal preparation. Young adult cats were induced
with an intramuscular injection of a mixture of ketamine (20 mg/kg) and acepromazine (0.4 ml) and received a subcutaneous injection of atropine. Anesthesia was maintained with periodic intravenous injections of 60 mg 
-chloralose dissolved in a warm 1:3 mixture of
propylene glycol and saline that were repeated when withdrawal reflexes
to toe pinches returned and sometimes supplemented with diazepam to
obtain more complete flaccidity of the limbs. Body temperature was
maintained at 37°C. A tracheotomy was performed and both ear canals
were exposed. DCN and/or DAS were visualized via a dorsal approach and
cerebellar aspiration. The electrode was held by a microdrive fixed to
the skull with a lucite holder and controlled from outside the
sound-shielded room. It was aimed at the free surface of the DCN or at
the DAS where it crosses the dorsal surface of the inferior cerebellar
peduncle to descend along the surface of the fourth ventricle.
Data collection and analysis. Stimuli were timed and
generated with a 16-bit digital stimulus system (Olson et al., 1985) driving dynamic phones that were part of a closed acoustic assembly (Chan et al., 1993). This assembly, also containing a calibration probe
tube, was connected to tight-fitting hollow ear pieces inserted into
the cut ear canals on both sides. Single units were recorded with
glass-insulated tungsten electrodes of ~3-4 M
(MicroProbe) or
glass micropipettes (~20 M). The neural signal was amplified, filtered, displayed, and discriminated with conventional methods. Standard pulses were sent to the computer, which provided on-line visualization of poststimulus time histograms (PSTHs) and various response curves based on average firing rate or response synchronization.
For each well isolated unit characteristic frequency (CF: frequency
with lowest excitatory threshold), response to broadband noise and
presence of inhibitory sidebands (if spontaneous activity was present)
were assessed with a computer-controlled search program. Spontaneous
rate (SR) and CF were then quantitatively determined with a response
area program, which presented tone bursts (duration/repetition intervals were typically 50/200 or 100/500 msec) at many
frequency/sound pressure level (SPL) combinations, or a tuning curve
program that tracked the excitatory threshold (duration/repetition
intervals were 50/100msec). Rate-level functions were obtained to (1)
short tone bursts at CF (25/100 msec, 
200 repetitions, rise/fall
times 1.6 msec), (2) long-duration tone bursts at CF (100/500 msec or 200/1000 msec, rise/fall 3.9 or 4 msec, usually 40 repetitions in 5 or
10 dB increments), and (3) broadband noise bursts (40 kHz wide, other
parameters as in (2). Stimulus levels for tones are specified in
decibel SPL (sound pressure level re 20 µPa). Sound
levels for noise are attenuator settings (decibel, arbitrary reference), which are close (maximum difference of 11 dB) to noise levels re 20 µPa computed by integrating the
stimulus energy, corrected for acoustic calibration, over a one-third
octave band centered on CF.
Responses to these initial tests allowed classification of cells, based
on a modification of the schemes of Evans and Nelson (1973) and Young
and Brownell (1976), as described previously (Joris, 1998). Briefly,
four major categories were defined. Type IV responses showed
spontaneous activity that was mostly inhibited by pure tones at the CF,
so that rate-level functions obtained at CF were nonmonotonic, whereas
broadband noise was usually excitatory at all stimulus levels. Type III
responses resembled type IV responses but their response to CF tones
was not strongly nonmonotonic. For reasons outlined earlier (Joris,
1998), we refer to type III and IV classes as one inclusive
"III+IV" group. Type II responses had no spontaneous activity and
were well driven by CF tones but not by broadband noise. Finally,
responses were classed as Oc based on the PSTH to short CF
tone bursts, the expansive tonal rate-level function, and the strong
response to noise.
Data on Oc cells in previous studies were obtained mainly
in the PVCN. A small number of these cells occur in the DCN (Godfrey et
al., 1975b; Joris et al., 1992), but the main reason for including the
Oc response type in the current analysis is the strong
projection of these cells to DCN (Smith and Rhode, 1989; Joris et al.,
1992). Thirteen of the 14 Oc cells reported here were
recorded in the stria, and one was recorded in the DCN. As they cross
the inferior cerebellar peduncle and course centrally, the axons of
Oc cells form a bundle that is separate from the axons of
fusiform and giant cells [Osen et al. (1990), and our unpublished
results], and it is a matter of definition whether one considers these
axons to be part of the DAS or the intermediate acoustic stria or a separate bundle altogether. For convenience we refer to our
recordings in the stria as "DAS recordings" (see Joris, 1998).
Temporal behavior was studied with 20 µsec rarefaction clicks
(repetition interval 100 msec, 200 repetitions) and AM stimuli (600/1000 msec, 20 or 40 repetitions). A tonal carrier of frequency fc (= CF) was digitally multiplied with a
low-frequency sinusoidal modulator of frequency
fm according to the equation
s(t) = [1 + m sin
(2
fmt)] sin
(2fct), with modulation depth
m = 1. Magnitude (Rm) and
phase (
m) of synchronization of the response to
the envelope frequency of the AM stimulus were quantified with vector averaging (Goldberg and Brown, 1969). Rm (also
called vector strength or synchronization index) is 1 when all spikes
occur at one particular envelope phase; for randomly timed spikes
Rm is 0. In the calculation of
Rm the initial 10 msec of the response were
discarded to remove the effect of the stimulus onset transient.
Synchronization level functions (Rm and
m as a function of SPL) were obtained with fixed
fm (usually 100 Hz) by increasing the stimulus
level in 5 dB steps from below threshold to ~80 dB. From this
function an SPL was found at which the response was strong both in
terms of average firing rate and in terms of synchronization to
fm. Modulation transfer functions were then
obtained by keeping SPL fixed at that level and varying
fm in linear steps between ~10 and 2000 Hz.
Examination of binaural sensitivity in the DCN is complicated by the
combination of weak contralateral influences and complex ipsilateral
responses, which often include nonmonotonic and mixed excitatory/inhibitory components. We report only binaural effects that
could not be interpreted as a result of ipsilateral stimulation through
acoustic cross talk: this biased our sample toward type III+IV cells,
which usually have spontaneous activity and low ipsilateral thresholds
(see Results). Precautions were taken to minimize acoustic cross talk
through the stimulus system (Gibson, 1982), and control experiments in
the auditory nerve confirmed the high level of acoustic isolation, also
helped by the high-frequency bias of DCN. Comparison of rate-level
functions with ipsilateral and contralateral noise bursts (same
parameters as in DCN-DAS experiments; e.g., see Fig. 9C),
obtained for nerve fibers with CFs between 2.5 and 21 kHz, showed that
interaural attenuation was 60 dB.
Control experiments. We contrast the responses obtained in
DCN and DAS with responses in the auditory nerve and anteroventral cochlear nucleus (AVCN). Responses to AM stimuli are compared with
published auditory nerve data (see Figs. 2C, 6, 8) (Joris and Yin, 1992). Responses to contralateral noise bursts and ipsilateral CF tones, clicks, and noise bursts (see Figs. 2A,B,
9C, 13) were obtained from two auditory nerve experiments
and one AVCN experiment (this was not the main focus of these
experiments). The experimental and analytical procedures were almost
identical to the DCN-DAS experiments, the main difference being that
pentobarbital anesthesia was used (Joris and Yin, 1992, 1998). Again,
effects of contralateral stimulation were primarily looked for as an
inhibition of SR, and these experiments were therefore biased toward
cells with high SR.
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RESULTS |
Data were obtained for several hundred cells from DCN (four
animals), DAS (six animals), or combined DCN-DAS (three animals) recordings. Cells were classified according to the response map and
PSTH scheme, as described in Joris (1998). Only cells in the main
response classes (types II, III, and IV, or Oc), for
which temporal or binaural measures were available and which were
driven by the ipsilateral ear, are retained for the present report
(n = 114). In terms of the binaural and temporal
response measures discussed here, the data did not suggest notable
differences, within the type III+IV group, between the DCN and DAS
recordings. We therefore pool the data from DCN and DAS recordings in
most population figures. Based on these and other (Joris, 1998)
similarities, and on independent anatomical evidence derived from
intra-axonal labeling (our unpublished observations), it is unlikely
that the DAS data reported here are contaminated by recordings from
descending fibers.
Response latencies
Various kinds of broadband and filtered noises have been used in
the physiological dissection of the DCN, but with the exception of the
early study of Godfrey et al. (1975b), responses to transients have not
been studied systematically. Figure 1
shows representative click responses of type III+IV
(A-E) and Oc (F, G) units to
20 µsec rarefaction clicks over a range of SPLs. Oc units
responded with one or more modes of increased firing probability that
were very well timed and had short latency. Type III+IV cells also responded with several modes but with longer latency and poorer timing.
Moreover, the response of the latter cells sometimes had unusual
features such as a latency increase with increasing SPL (Fig.
1A,B, compare left and right histograms), and a first
excitatory mode that was preceded by inhibition of spontaneous
activity.
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Figure 1.
Responses of fibers in the DAS to 20 µsec
rarefaction clicks. A-C, E, Type IV; D,
type III; F, G, type Oc. Suprathreshold
levels (dB) are indicated above each PSTH histogram. For cells in
A and B, responses at two levels are
shown. Note that the latency of the excitatory response at low
suprathreshold levels (left) is shorter than at high
levels (right). Number of bins = 250. Number of
repetitions: A, 500; B-D, 1000;
E-G, 200. Responses B-G were obtained
from the same animal. Ordinate scales on bottom apply to all
histograms. A response of one spike/click, exactly timed in one 40 µsec bin, would give a response of one spike/stimulus per bin.
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Click response latency at each SPL was determined for type III+IV and
Oc cells from 3-point smoothed PSTHs (40 µsec binwidth) as the poststimulus time at which discharge rate reached 20% of the
maximum driven rate (= absolute rate 
SR) at the peak of the
first response mode. Comparison (Fig.
2A) of minimum click latencies in 17 type III+IV units with eight Oc units
shows systematically shorter values [Mann-Whitney U
(MW-U), p < 10
4] for the latter type. Latencies were only
~1 msec longer for Oc cells than for auditory nerve
fibers of similar CF.
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Figure 2.
Comparison of latencies in DCN, DAS, and auditory
nerve, measured for three types of stimuli. A, Minimum
click latency. Type II cells were unresponsive to clicks and are thus
not represented. B, Minimum latency to 25 msec tone
bursts at CF. Symbols carrying upward arrows indicate
responses for which shortest latency was >10 msec. C,
Group delay measured from the slope of the phase-frequency function
derived from responses to amplitude modulation. Datapoint for one type
II cell (CF = 9.5 kHz) was shifted to lower CF to avoid overlap.
Auditory nerve data in A and B are from a
single experiment, whereas those in C are from the study
by Joris and Yin (1992). Measures in C are corrected for
acoustic delay, which was ~0.28 msec (~0.40 msec for auditory nerve
experiments in C) as measured from the phase-frequency
slope of the acoustic calibration curve.
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The click latencies measured here correspond well with the ranges
quoted by Godfrey et al. (1975a,b) if compared as follows: their
Pauser, Buildup, and Chopper categories with our III+IV class and their
OL class with our Oc class. Godfrey et al.
(1975b) also described DCN cells with "on-type S" responses, many
of which did not respond to clicks. The response to a sustained noise
stimulus was not tested in that study, but the PSTH, shape of the tonal rate-level function, and absence of spontaneous activity of the cells
reported by Godfrey et al. (1995b) are consistent with the current type II definition (Young and Voigt, 1982). To verify the
finding of Godfrey et al. (1975b), we presented clicks to type II
cells. In 10 cells, isolation of the spike was good enough to avoid
contamination with the click-evoked field potential. Only one cell
showed a significant response (one spike on ~50% of trials) but only
at the highest output level attainable. A few other cells showed an
occasional spike (maximum was 12 spikes in 200 repetitions), but most
cells did not respond at any level. The absence of click responses is
intriguing because it requires a very short latency inhibition that
precedes the excitatory effect of auditory nerve input to type II
cells, but that itself is also driven by the auditory nerve. Parsimony
suggests that the same source of inhibition prevents firing of type II
cells to broadband noise (Young and Voigt, 1982) and to transient
broadband stimuli.
To enable a latency comparison for a larger sample of cells that
includes type II cells, we measured latencies to short CF tone bursts.
Onset latency was calculated for a wide range of SPLs, with the same
method as that used for click responses, and for each cell we noted the
shortest value, which generally occurred at the highest SPL presented.
As shown in Figure 2B, there is a wide range and
considerable overlap in the latencies of type II, III, and IV cells
(n = 12, 36, 27, respectively; MW-U between these classes was not significant), but Oc latencies
(n = 14) were again consistently short and differed
significantly from the other DCN classes taken together
(MW-U, p < 106).
Various pieces of evidence suggest that Oc cells are
inhibitory and may provide a strong input to both type II cells and
weaker input to type IV cells (see Discussion). The short latency of Oc responses to clicks and tones (and also to AM; see below
and Fig. 2C) corroborates this proposal; it may explain both
the absence of click responses in type II cells and the early
inhibition of SR in some type IV cells.
Response to amplitude modulation
Impulsive or step changes in intensity as in clicks and tone
onsets do not afford the study of ongoing temporal properties of
high-CF neurons to sustained stimuli, and often present recording difficulties because of a field potential associated with stimulus onset. AM stimuli are complementary and convenient in both these regards. Examples of responses to AM with increasing SPL are shown in
Figure 3 for an Oc
(left column), type II (middle column), and type
IV (right column) cell. The rate-level functions to CF tones
and broadband noise (bottom panels) show the defining
characteristics of these response classes. The tonal rate-level
function is expansive for the Oc cell, excitatory but with
negative slope at mid and high SPLs for the type II cell, and mostly
inhibitory for the type IV cell. The response to noise is very large in
the Oc cell, absent in the type II cell, and intermediate
in the type IV cell. The rate-level functions of Oc and
type II cells to AM tones are similar to those for the short tone
responses, albeit with reduced driven rate, as observed previously with
unmodulated long tone bursts (Joris, 1998). The average rate of the
type IV cell was inhibited by CF tones but exceeded SR in response to
AM. These differences in average firing rate to tones versus AM were
generally observed and are interesting in themselves, because it is
unlikely that they are based on a spectral difference. For example,
rate-level functions of type IV cells to noise bands of the same
bandwidth as the AM stimuli used here (200 Hz) are similar to
rate-level functions in response to CF tone bursts (Nelken and Young,
1994, 1997). However, we did not obtain responses to long unmodulated tone bursts and are therefore unsure to what extent the rate changes as
in Figure 3 are caused by the stimulus envelope rather than the longer
duration and/or repetition interval of the AM stimulus.
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Figure 3.
Responses to AM tones for an
Oc (left column), type II (middle
column), and type IV unit (right column).
Bottom panels show rate-level functions to unmodulated
CF tone bursts (+; duration 25 msec for A, B, 100 msec
for C), to AM tones (×), and to broadband noise
( ). Middle panels (D, E, F)
show the synchronization-level (Rm,
 ) and phase-level (m,  ) function calculated
from the same AM response. Synchronization magnitude is quantified with
the vector strength Rm, a
dimensionless quantity varying between 0 and 1. Phase m
is given in cycles and is not shown if Rm is
not statistically significant (indicated with  ). Histograms
(top) are cycle histograms at three selected SPLs,
indicated with arrows in the middle
panels. Modulation depth of AM tones was 100%, carrier
frequency was at CF, and modulation frequency
(fm) was 100 Hz. The
Oc and type IV unit were recorded from the stria; the type
II was recorded from the DCN. CFs were 24.8, 9.5, and 8.8 kHz,
respectively.
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Temporal measures derived from the AM responses are shown in Figure 3
(middle panels). The magnitude of synchronization
(Rm; ) to the modulation frequency of
100 Hz is shown for a range of SPLs. Open circles indicate significant
synchronization, as measured with the Rayleigh test
(p < 0.001); for those SPLs the phase of
synchronization (m; ) is also shown. Period
histograms (firing rate as a function of modulation phase) are shown in
the top row for selected SPLs, indicated by arrows in the middle
panels. Oc cells invariably showed precise phase-locking to
fm over the entire range of SPLs tested. As
illustrated by the example (Fig. 3, left column), period
histograms grew more asymmetrical with increasing SPL and developed a
small phase lead, but overall these responses were remarkably stable in
magnitude and phase over a wide range of SPLs. In contrast,
synchronization of type II and type III+IV cells to the AM envelope was
highly variable both within and across cells. The type II (middle
column) and type IV (right column) responses in Figure
3 are well synchronized to the envelope at low SPLs, with phase similar
to that of the Oc cell. As SPL was increased, however,
synchronization magnitude in both response types showed nonmonotonic
behavior accompanied by large changes in phase (Fig.
3E,F). At low suprathreshold levels, both cells
discharged maximally in the second half of the period histogram (0.5-1
cycles), whereas at high SPLs there was a trough at these phases.
Moreover, as is obvious from the period histograms at intermediate
levels (illustrated in Fig. 3 at 55 dB for type II and at 25 dB for
type IV), the response can be so nonlinear that synchronization at the
envelope frequency does not adequately describe the response at these
levels. For example, over the range of SPLs where the synchronization
to the first harmonic (=fm) fell to a
minimum and showed the large shift in phase, both cells showed a large
second harmonic (data not shown) that exceeded the first harmonic in amplitude.
Nonmonotonic changes in synchronization magnitude and phase were seen
in most type II (7/10) and type III+IV (6/8) cells; in the remaining
cells, envelope synchronization was monotonic or was not studied over a
wide enough range. Although the examples of Figure 3 are
representative, the exact form of the synchronization and phase
nonmonotonicities in type II and III+IV cells was idiosyncratic. A more
consistent picture, especially for type II cells, is obtained by
inspection of period histograms, shown in Figure
4 for six examples from each class. At
low (
45 dB) SPLs (Fig. 4A-C, left columns), all cycle histograms are unimodal with similar phase (although the phase is consistently lowest for Oc
cells and highest for type IV cells). The similarity in phase at low
SPLs in these three cell types is expected; the cells shown have CFs of
>4.5 kHz (one exception; see legend to Fig. 4) and thus undergo small differences in cochlear delay (Joris and Yin, 1992); moreover, phase
shifts caused by delay differences are small because of the low
modulation frequency used (100 Hz: each one-tenth of a cycle in the
period histograms thus corresponds to 1 msec).
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Figure 4.
Examples of period histograms, binned
at the modulation frequency fm, for
six cells of each response type. For each cell, two histograms are
shown: at a low SPL (left, 45 dB) and a high SPL
(right, 65 dB). fm was 100 Hz except for one low-CF Oc cell (top row,
CF = 1.4 kHz) for which 50 Hz was used. C,
Histograms on the first and second row were from type III cells; others
were from type IV cells.
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At high (65 dB) SPL (Fig. 4A-C, right
columns) the histograms are very diverse and can be dominated by
higher harmonics, but certain commonalties within each response class
are apparent. For Oc cells, the basic period histogram
shape and average phase are similar to those at low SPLs, except for an
increased asymmetry and superimposed chopping in some cells. In type II
cells, the dominant mode at low SPLs is replaced by a trough flanked by
one or two modes at high SPLs, and in type IV cells there is a general increase in complexity, sometimes revealing multiple modes. For all
cells, at all SPLs, we examined spike timing, relative to envelope
phase, over the entire stimulus duration. There was sometimes a slight
increase in phase lag of the response modes with increasing poststimulus time, but the basic shape of the period histogram was
present throughout the duration of the response.
The AM synchronization behavior of these three response types deviates
strongly from that of auditory nerve fibers: for Oc cells
in terms of the high gains achieved, and for type II and III+IV cells
in terms of the strongly nonlinear response at mid and high SPLs.
Auditory nerve fibers sometimes show an increase in envelope
synchronization at very high SPLs, but this occurs only in fibers with
low CF and is not accompanied by a shift in m (Joris and
Yin, 1992). Intrinsic properties can affect temporal behavior (Manis,
1990; Zhang and Oertel, 1993; Feng et al., 1994) and may contribute to
the change in shape of the cycle histogram with SPL, e.g., as seen in
the Oc cells, but undoubtedly the complex period histograms
are also shaped through interaction of excitatory and inhibitory inputs
that have phase-locked responses with different harmonic content.
Period histograms of type II cells at high SPLs are consistent with a
tightly phase-locked inhibitory input, e.g., from Oc cells,
at roughly the same phase as an excitatory input that is temporally
more dispersed. Comparison at low and high SPLs (40 and 80 dB, or
nearest available values) shows (Fig. 5) that the response phase of Oc cells is restricted in
distribution and changes little over a 40 dB range: the points are
close to the diagonal of equality. This is not the case for type II
cells, which show a restricted phase distribution at low SPLs but a
more dispersed distribution at high SPLs. Note that at these high SPLs, at which Oc cells show their highest discharge rates
(compare Fig. 3A), significant synchronization of type II
cells occurs mostly at phases outside the phase range of Oc
cells. The even greater complexity in the type IV histograms likely
reflects phase-dependent interactions of multiple excitatory and
inhibitory sources, including the type II cells, which are inhibitory
to type IV cells, and parallels the previously described complexity of
responses to manipulations in the frequency domain, which are also
linear at low SPLs and increasingly nonlinear at mid and high SPLs
(Nelken and Young, 1997). The lowest SPLs at which multimodal period
histograms started to appear are also in line with this interpretation.
For type II cells this was at a median SPL of 25 dB, which is 5 dB higher than the median rate threshold of the Oc cells in
this sample, and in type III+IV cells multimodal period histograms started to appear at a median SPL of 20 dB, which is 5 dB higher than
the median rate threshold of type II cells in this sample.
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Figure 5.
Comparison of phase to
fm, for type II and Oc
cells, at low (abscissa) and high (ordinate) sound level. Each
datapoint shows response phase for one cell at 40 and 80 dB SPL, or at
the nearest SPL that gave significant synchronization (low SPL was
taken at 45 dB in 1 cell; high SPL was taken at 70 dB in 3 cells).
Distribution of phases of Oc cells was within a narrow
range at both low and high SPL (range = 0.26 and 0.23 cycles,
respectively; median phase = 0.51 and 0.45 cycles). The
distribution of type II cells was within a narrow range at low SPL
(0.37 cycles; median phase = 0.72). At high SPL it was more
dispersed and showed an absence of values over the range at which most
Oc cells responded, consistent with an inhibitory input of
Oc to type II cells.
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The nonmonotonic and nonlinear behavior just described was not
emphasized in previous studies of AM responses in the DCN. For example,
Rhode and Greenberg (1994) found Pauser/Buildup units "to be
exceptionally capable of encoding AM signals as long as the
fm was relatively low (i.e., < 600 Hz)." The
scant data that exist on AM responses in type II cells also show good
envelope phase-locking (Kim et al., 1990; Zhao and Liang, 1995). It is important, therefore, to rule out differences in experimental variables
(e.g., anesthesia, our inclusion of recordings in DAS) as a cause of
discrepancies. In the following three figures, we proceed with a linear
analysis of phase-locking and find that within the limits of that
analysis, our results are consistent with previous reports.
For each cell we measured the maximal Rm value,
defined as the maximum in the synchronization level function obtained
with fm of 100 Hz. Oc cells had
uniformly high gain when compared with auditory nerve fibers (Fig.
6). High maximum values were also found
in some type II and III+IV cells, but the values for these cells were
more varied. Median values were 0.93 for Oc
(n = 12), 0.79 for type II (n = 10),
and 0.75 for type III+IV (n = 7).
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Figure 6.
Maximum synchronization values to
fm, for DCN responses classes and a
population of auditory nerve fibers [auditory nerve data are from
Joris and Yin (1992)].
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A limited number of cells were held long enough to obtain complete
modulation transfer functions (MTFs), which characterize the dependence
of envelope synchronization on modulation frequency. AM stimuli of
increasing fm were presented at low
suprathreshold SPLs, where single-mode cycle histograms were obtained
(Fig. 3D-F), and also at higher SPLs if time
allowed. From the 45 MTFs obtained we selected one function for each
cell, shown in Figure 7. When multiple
MTFs were available we selected the function with the highest maximal
Rm value. In one type II and one type IV cell there was a sharp notch in envelope synchronization over a narrow fm range, but for the remaining cells the MTF
could be described as low-pass or bandpass. Type III+IV cells showed
maximal synchronization near 100-200 Hz and generally had lower
synchronization values than Oc or type II cells. The most
striking difference between response classes was in the width of the
MTFs; widest in Oc, narrowest in type III+IV, and
intermediate in type II cells. The upper cutoff frequencies, taken at 3 dB down from the maximum (Joris and Yin, 1992), are compared with
identical measurements from a population of nerve fibers in Figure
8. For CFs >10 kHz, the cutoff
frequencies of Oc cells were within the range of auditory
nerve fibers, whereas the cutoff frequencies of type II and III+IV
cells were well below the lowest cutoff frequencies in nerve fibers of
similar CFs. Thus, Oc cells stand out by a consistently
high synchronization gain to the envelope frequency (Fig. 6), over a
wide range of SPLs and fm values.
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Figure 7.
A, Modulation transfer functions
for different response classes in DCN. Oc,
Dashed lines; type III+IV, solid lines.
Only one cell in the III+IV group was type III. Range of SPLs was
20-55 dB for type II (n = 8), 10-50 dB for type
III+IV (n = 5), and 30-70 dB for Oc
(n = 6). B, Examples of cumulated
phase-frequency functions for cells of similar CF of each response
type. CFs were 25.9 (type IV), 24.7 (type II), and 23.6 (Oc); SPL was 30 dB.
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Figure 8.
Comparison of cutoff-frequencies of modulation
transfer functions in auditory nerve [AN; data from
Joris and Yin (1992)] and the DCN, as a function of characteristic
frequency. Some of the type IV and Oc units were recorded
in the DAS. The type II cell with notched MTF in Figure
7A is not included.
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Figure 7B shows three examples of phase-frequency functions,
obtained by accumulating response phase as a function of modulation frequency, for cells with a similar CF. Phase values are only graphed
over the range of significant response modulation. The three functions
converge to a y-intercept near 0.25 cycles, consistent with the sine
starting phase of the stimulus envelope (see equation in Materials and
Methods), and clearly differ in slope. This slope reflects the total
delay accrued between acoustic stimulus and cell discharge and was
measured by fitting a linear regression through the phase-frequency
functions as described in previous publications (e.g., Joris and Yin,
1992). The regressions all had r2 values
>0.987. Figure 2C shows the slopes of the linear
regressions as a function of CF. Again, Oc cells show the
smallest values, which differed significantly (MW-U,
p < 0.01) from other DCN cells.
Response to contralateral stimulation
Mast (1970) showed that many DCN cells in chinchilla were
inhibited by contralaterally presented tones, at thresholds close to
the ipsilateral excitatory threshold (median difference 7 dB) and with
similar latency. Hochfeld (1973) presented similar findings for the
cat, although with greater threshold (mean of 31 dB) and latency
differences (mostly 10-20 msec). Judged on location, presence of
spontaneous activity, and PSTH shape, most of these cells were likely
type III+IV cells. Young and Brownell (1976) also found predominantly
inhibitory contralateral effects in DCN of the decerebrate cat and
reported that effects were weaker and more variable for contralateral
tones than for broadband noise. Indeed, they reported that the response
to binaural noise was intermediate between the ipsilateral (excitatory)
response and the contralateral (inhibitory) response, which suggested a
functional relevance for these binaural interactions in natural
listening conditions.
We studied effects of contralateral or binaural stimulation in 20 DCN
and 50 DAS units. The easiest way to detect an effect was by examining
SR while stimulating the contralateral ear with broadband noise.
Examples are shown in Figure 9 for a type
IV (A) and a type III (B) cell. In
both cells contralateral noise () suppressed SR to levels near zero.
A summary for all cells tested is shown in Figure
10: circles indicate SR, and the
"T" and inverted-T symbols indicate maximum firing rate to
ipsilateral and minimum firing rate to contralateral noise,
respectively, obtained from rate level functions as in Figure
9A,B. In all units tested (n = 52), we
consistently found inhibition of SR by contralaterally presented
broadband noise. The inhibition was not a spurious effect caused by
acoustic cross talk, because the dominant effect of contralaterally
presented noise was opposite to that of ipsilaterally presented noise,
i.e., inhibition rather than excitation, and because the threshold for
contralateral inhibition was usually close to that of ipsilateral
excitation (on average 8 dB higher than ipsilateral excitatory
threshold; range 20 to + 30 dB). Effects on SR were hard to detect
with contralateral tones, delivered as a search stimulus over a range
of frequencies and SPLs. Of eight units tested quantitatively with
monaural contralateral tones, at a frequency equal to the ipsilateral
CF, only half showed an inhibitory effect at high SPLs (see below and
Figs. 11, 12).
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Figure 9.
Effects of contralaterally presented
broadband stimuli on spontaneous and ipsilaterally evoked activity.
A-C, Responses to monaural and binaural (equal level)
stimuli. A, DAS type IV cell, CF = 8.8 kHz.
B, DAS type III cell, CF = 5.7 kHz.
C, Auditory nerve fiber, CF = 11.8 kHz.
D, Noise interaural level difference
(ILD) functions for the same cell as B.
The level of the ipsilateral noise burst was held constant at the level
indicated in the caption, whereas the contralateral level was varied.
In all cases binaural stimuli were gated simultaneously, and
differences in phone maximum output levels were <10 dB, as measured in
a one-third octave band around the CF. Duration was 25 msec for CF
tones (A, B: +) and 50 or 100 msec for noise bursts. The
upward inflections of the rate-level functions at the highest
contralateral levels (A, 90 dB; B, D, 80 dB) were interpreted as the threshold of acoustic cross talk.
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Figure 10.
Summary of spontaneous rate, maximal rate to
ipsilaterally and binaurally presented noise, and minimal rate
to contralateral noise (DAS recordings, ; DCN recordings,  ). The
first seven cells were tested only with monaural contralateral noise.
The effect of binaural noise was tested in the last 14 cells (cells
39-52). Within groups, cells are ranked according to increasing
response to ipsilateral noise (increasing spontaneous rate for cells
1-7). Inhibition to binaural noise was observed in only one cell (cell
39). Some cells were not classified because of short recording time
(n = 16; almost all in DAS). All other cells were
type III+IV.
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Figure 11.
The excitatory response of a type III cell to an
ipsilateral CF tone of increasing SPL is inhibited by a contralaterally
presented broadband noise (left column) or tone
(right column). The ipsilateral CF tone (10 kHz) was
identical for both columns: it started at 0 msec and was 200 msec in
duration, and its SPL was increased in 10 dB steps, as indicated on the
right. The contralateral stimulus was delayed by 100 msec relative to the ipsilateral stimulus, its duration was 50 msec
(brackets on top), and it was at a
constant level (left, 59 dB, measured over one-third
octave centered at CF; right, 80 dB SPL). These
responses are from the cell with the largest inhibition to
contralateral tones in our sample.
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Because of the pervasiveness of inhibition by contralateral noise, a
control experiment with identical stimuli was performed in the auditory
nerve. Ten high-SR and two medium-SR auditory nerve fibers were tested
(CF range, 2.5-21.0 kHz) with monaural ipsilateral and contralateral
noise over a wide range of SPLs. In none of these was there was a
detectable suppression of SR by contralateral stimulation, as
illustrated for a high-SR fiber in Figure 9C.
The inhibition of spontaneous activity by contralateral noise was not
only consistently present and low in threshold; it was also profound,
diminishing firing rates to low values in most cells (Fig. 10: median
decrease in firing rate = 29 spikes/sec, median spontaneous
rate = 35 spikes/sec). This was not generally the case for
inhibitory effects on the response evoked by ipsilateral stimuli. In 14 cells (all type III+IV), we presented noise binaurally at an equal
level over a range of SPLs. Two examples are shown in Figure 9
(A,B, diamonds). The response to binaural stimulation was
lower than that to monaural ipsilateral stimulation, but in relative
terms the effect was small, despite the clear inhibition of spontaneous
activity by monaural contralateral stimuli. The × symbols in
Figure 10 indicate the maximum rate to binaural stimulation for all
cells. The inhibitory effect, measured as the difference between the
maximum ipsilateral response and maximum binaural response, did not
scale with ipsilateral response magnitude. The median decrease in
firing rate was 22 spikes/sec. In only one cell (Fig. 10; cell ranked
number 39) was the binaural response inhibited below spontaneous rate.
Before concluding that the inhibitory effect of the contralateral ear
was weak, we further tested type III+IV cells with more natural
interaural differences. To free-field sources, head and pinnae of the
cat generate interaural level differences (ILDs), which can be
~20-30 dB at high frequencies (Irvine, 1987; Musicant et al., 1990;
Rice et al., 1992). We obtained ILD functions by holding the level at
the ipsilateral ear constant while varying the level at the
contralateral ear. In all cases examined (n = 14),
firing rate decreased with increasing contralateral level, but the
decrease was much smaller than that obtained in well characterized binaural cells, e.g., in the LSO, where inhibition is virtually complete at 0 ILD (Boudreau and Tsuchitani, 1968). The largest effect
was seen in the cell of Figure 9B, and a series of ILD functions for this cell is shown in Figure 9D, with
ipsilateral level as the parameter. For each function the level of the
ipsilateral ear was held constant at the value indicated, whereas the
level of the contralateral ear was increased from positive ILDs
(defined as contralateral level > ipsilateral level) to negative
ILDs. Even for positive ILDs near the upper limit of the physiological range, the cell was not completely inhibited. Moreover, unlike LSO
cells, the largest inhibitory effect was a nearly equal number of
spikes/second across functions, independent of ipsilateral level. This
was particularly evident when the functions in Figure 9D
were graphed (data not shown) as a function of contralateral SPL, which
was varied over the same range for all functions. The largest
inhibitory effect, measured as the difference in firing rate between
maximum and minimum of the ILD function, on average was 62.3 spikes/sec
(range, 48.3-76.0) for Figure 9D (average for five other
cells was 32.5 spikes/sec; range, 19.3-52.5).
The rather weak binaural effects described so far do not preclude that
contralateral ear stimulation is significant in a full-cue, natural
sound field, where different azimuthal sound source positions generate
ILDs with reciprocal level changes in the two ears as well
as spectral differences (Musicant et al., 1990). Limited data (not shown) to "virtual space" stimuli, obtained to binaural noise filtered by head-related transfer functions (technique as described in Delgutte et al., 1995), suggest indeed that inhibition of
type III+IV cells by contralateral ear stimulation can be profound within the physiological range of cues, if the full complement of cues
is present in their natural combination.
Various descending projections to the CN exist (Conlee and Kane,
1982; Brown et al., 1988; Weedman and Ryugo, 1996; Ostapoff et
al., 1997), and an estimate of the latency and time course of the
contralateral inhibition may narrow down the possible sources involved.
We presented a contralateral stimulus during the sustained portion of
the response to long ipsilateral CF tones in 10 type III+IV cells. A
range of ipsilateral and contralateral settings was explored, and in
most cases a setting could be found resulting in a sustained reduction
of driven rate with a fast time course of onset. Figure 11 shows a
level series of responses of one cell to a 200 msec CF tone,
while a broadband noise burst (left column) or tone
of the same frequency (right column) was delivered to the
contralateral ear at a constant level but with a 100 msec delay. The
inhibition is stronger for contralateral noise than tones and is only
profound for spontaneous activity or at low ipsilateral SPLs, but its
onset is fast. Three more examples are shown in Figure
12A,B (contralateral
noise) and C (contralateral tone). Inhibition reached its
full strength within ~20-30 msec of contralateral stimulus onset,
but not enough stimulus repetitions were available to derive a more
precise estimate of the onset of inhibition. We attempted to
estimate this onset with two additional procedures. First, we tried a
technique used earlier on cells in the LSO (Joris, 1996) that are also
excited by one ear and inhibited by the other. A sustained CF tone was
presented to the excitatory ear and an AM tone or AM noise to the
inhibitory ear, and the average phase of the response was calculated.
Measurement of cumulated phase as a function of modulation frequency
then gives an estimate of the contralateral inhibitory group delay (compare Fig. 7B). Unfortunately, the contralateral
inhibitory effect appeared sluggish and did not follow the envelope of
contralateral AM tones or AM noise (Fig. 12D,E). Only
in one cell
strongly inhibited by contralateral tones (Fig.
12C)was significant envelope phase-locking up to 250 Hz
obtained after extensive exploration of binaural parameters (Fig.
12F). The group delay relative to the onset of the
contralateral stimulus was 5.7 msec. Comparison of monaural and
binaural responses (e.g., response phase to ipsilateral and contralateral AM) indicated that the phase-locked response was not
caused by acoustic cross talk. Second, we selected 20 type III+IV cells
that showed inhibition of spontaneous activity with a well defined time
course and averaged their individual PSTHs to an identical stimulus
(100 msec contralateral broadband noise burst at 70 dB; this was the
highest level at which none of the cells showed evidence of acoustic
cross talk). This population PSTH was then compared with a population
PSTH for the same stimulus presented ipsilaterally (Fig.
13, bottom). The latency for
a 20% reduction in SR to contralateral stimulation was 6.6 msec,
whereas the latency for a 20% increase in firing rate to ipsilateral
stimulation was 3.8 msec. Figure 13 also shows population PSTH
histograms for auditory nerve fibers and cells in AVCN with
primary-like-with-notch (PLN) or chopper responses.
Inhibition of SR by contralateral noise was clearly present in
choppers, with a latency of 5.7 msec, but was not seen in auditory
nerve and PLN cells. Interestingly, a prolonged offset
inhibition was present in the type III+IV neurons for both ipsilateral
and contralateral stimulation, but not in the chopper cells.
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Figure 12.
Time course of contralateral inhibition in three
cells. Each row shows responses for one cell. The ipsilateral ear was
stimulated with a CF tone at a low SPL (A-F, 25, 20, 25, 10, 10, and 35 dB), which started at 0 msec and was 600 msec in
duration (300 msec in C). The contralateral ear was
stimulated after a delay of 100 or 200 msec (onset and offset indicated
by markers). A-C, Stimulation of the
contralateral ear with a broadband noise (A, B) or tone
(C, same frequency as ipsilateral ear) caused
inhibition. This inhibition was rapid in onset and was sustained over
the duration of the stimulus (100 msec). Contralateral levels were 85, 62, and 80 dB SPL. D-F, These same cells showed
inhibition to a 500 msec contralateral tone that was
amplitude-modulated at 50 Hz, but only for the cell shown in
F did the inhibition entrain to the stimulus envelope.
Contralateral levels were 80, 60, and 80 dB SPL. Response type,
recording site, and CF: top row, type IV in DAS, 14.7 kHz; middle row, type III in DAS, 4.3 kHz; bottom
row, type III in DCN, 10 kHz. Binwidth is 10 msec in A,
B; 5 msec in C; 4 msec in
D-F.
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Figure 13.
Population responses to ipsilateral and
contralateral noise in auditory nerve and cochlear nucleus.
PLN, Primary-like-with-notch;
CHOP, chopper. PSTHs are responses averaged across cells
to an identical stimulus (broadband noise at 70 dB, rise/fall time of 4 msec, starting at 0 and 100 msec in duration) at either the ipsilateral
(left column) or contralateral (right
column) ear. The same cells were used in construction of left
and right histograms (number of cells: AN, 11;
PLN, 3; III+IV, 20), except for
the chopper class (n = 2 for IPSI,
n = 6 for CONTRA). Binwidth is 1 msec. Scales for histograms on bottom apply to all
histograms in a column; note the difference in scale for left and right
column.
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The time course of contralateral inhibition in choppers and type III+IV
cells, and the absence of inhibition in the auditory nerve, exclude the
possibility that this inhibition is caused by olivocochlear suppression
of type I auditory nerve fibers. Such suppression has a time course
that is about an order of magnitude slower, and its effect on SR is
slight (Warren and Liberman, 1989a,b). It is questionable whether
descending inputs from midbrain or even superior olivary complex could
provide contralateral inhibition with sufficiently short onset latency,
but these sources may contribute to the later, sustained part of the
inhibition. Particularly in the cat, minimum latencies of olivocochlear
fibers are longer than the onset of contralateral inhibition in the CN
observed here (Liberman and Brown, 1986; Gummer et al., 1988; Brown,
1989), and the same applies to cells in the IC (Irvine and Jackson,
1983; Kuwada et al., 1984). The contralateral inhibition of cells in the LSO, which occurs via fast conducting axons and powerful synapses, has a minimum latency of ~4.3 msec [Joris and Yin (1998); group delay + acoustic delay], and estimates based on first spike latency using tones with 2.5 msec rise time are longer, at values >6 msec (Tsuchitani, 1997). Considering (1) the extra distance to the DCN, (2)
the longer rise time used here (4 msec), (3) the lack of evidence for
any known fast-conducting inhibitory pathway from the superior olivary
complex to the CN, and (4) the extensive projections from periolivary
cell groups to the CN (Ostapoff et al., 1997) and the generally longer
latencies that are recorded in periolivary regions (Tsuchitani, 1977),
it is unlikely that the short-latency contralateral inhibition of DCN
would be derived through a link in this complex.
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DISCUSSION |
Temporal properties
Physiological dissection of DCN circuitry has made use mainly of
spectral stimulus manipulations (for review, see Young, 1998). We
provide evidence that in the time domain, responses are consistent with
the circuitry proposed from these earlier experiments. Responses of
interneurons (type II) and projection neurons (type III+IV) to clicks
indicate a source of short-latency inhibition. The inhibition is
particularly strong in type II cells, most of which were completely unresponsive to clicks, but was more variable and transient in type
III+IV cells, which showed an excitatory response sometimes preceded by
inhibition. Because type II cells were not responsive to clicks, they
cannot be the source of the early inhibition to type III+IV cells. To
all stimuli tested, Oc cells had the shortest latency.
These cells are probably glycinergic and project to the DCN (Smith and
Rhode, 1989), and therefore they are a likely source of the
short-latency inhibition to type II and III+IV cells. A common source
of inhibition that is strong to type II and weaker to III+IV cells was
suggested earlier (Nelken and Young, 1994), and is consistent with
results from electrical stimulation of the auditory nerve (Shofner and
Young, 1985; O'Leary et al., 1994) and with numerous previous studies
(Smith and Rhode, 1985; Caspary et al., 1987; Snyder and Leake, 1988;
Oertel et al., 1990; Saint Marie et al., 1991; Evans and Zhao, 1993;
Zhang and Oertel, 1993, 1994).
Early studies found that the timing properties of the DCN were inferior
to those of the ventral CN (Lavine, 1971; Goldberg and Brownell, 1973;
Godfrey et al., 1975b; van Gisbergen et al., 1975a,b; Rhode and Smith,
1986b), but later studies emphasized good envelope phase-locking and
even proposed specific roles for the DCN in processing temporal
information (Kim et al., 1990; Frisina et al., 1994; Rhode and
Greenberg, 1994; Langner and Schreiner, 1996). If synchronization to
the envelope frequency of the AM stimulus is considered, our data on
type II and III+IV cells agree with previous studies in terms of high
maximal Rm values (Fig. 6) and low upper-cutoff
frequencies (Fig. 8) (Kim et al., 1990; Rhode and Greenberg, 1994; Zhao
and Liang, 1995). However, the most striking feature of these cells was
the increasingly nonlinear response to AM stimuli of increasing SPLs
(Figs. 3, 4). At low SPLs, period histograms showed a unimodal response
peak. With increasing SPLs, this peak was replaced in type II cells by
an inhibitory trough flanked by one or two excitatory modes, as would be expected from increasing recruitment of Oc cells, which
showed high synchronization values at all SPLs with little change in phase. In type III+IV cells the period histograms were even more complex, presumably reflecting an interaction of multiple sources of
inhibition and excitationwhose amplitude, time course, and phase
relationships changed with SPLswith intrinsic membrane properties.
The temporally nonlinear response of type II and III+IV cells differs
drastically from that of LSO cells, whose response to binaural AM
stimuli conforms well to a linear summation of ipsilateral excitatory
and contralateral inhibitory inputs (Joris, 1996).
Nonmonotonicities are present in some examples of the linear analysis
by Rhode and Greenberg (1994), but the coarse sampling as a function of
SPL and the absence of phase data make them less apparent. Complex
behavior in some DCN units was also reported by Zhao and Liang (1995)
and Schreiner and Snyder (1987). Our findings largely agree with these
studies in terms of the high gain often found to AM stimuli, but the
nonlinearity of the responses calls into question the functional use of
this envelope information. The complexities in envelope phase-locking
of type II and III+IV cells make these cells ill-suited as
straightforward "envelope encoders" (Langner and Schreiner, 1996).
Of course, it remains possible that envelope information at this level
is not encoded as "following" of the stimulus envelope waveform,
but rather in a more subtle form of temporal patterns within or across cells.
Binaural properties
Stimulation of the contralateral ear had weak but consistent
inhibitory effects. Contralateral noise bursts inhibited spontaneous activity of all type III+IV cells tested, in both DCN and DAS, but had
generally only weak effects on ipsilaterally evoked activity. Interaction of binaural stimuli was very different from that observed in the LSO (Boudreau and Tsuchitani, 1968): the maximal effect of
contralateral ear stimulation was a roughly constant decrease in firing
rate, independent of the ipsilateral SPL, as observed previously by
Mast (1970). Moreover, the contralateral effects appeared temporally
much more sluggish than those in the LSO (Joris and Yin, 1998).
Our results are consistent with those of Young and Brownell (1976), but
they differ in one respect. These authors reported that responses of
type IV cells to binaural noise differed significantly from ipsilateral
responses, which suggested a functional relevance for these binaural
interactions in natural listening conditions. However, we found that
responses to equal level binaural noise bursts were generally close in
firing rate to the monaural ipsilateral response (Figs.
9A,B, 10). We tested a small sample of type III+IV cells
with additional binaural paradigms. The results suggest that binaural
effects may nonetheless be significant in a natural setting, where ILDs
are combined with spectral cues, but more work is needed to
substantiate this finding.
The inhibition through the contralateral ear had short latency but was
temporally sluggish, as was apparent in the difficulty to obtain
inhibition phase-locked to amplitude-modulated noise or tones (Fig.
12D-F). The weakness and sluggishness of
inhibition made a precise latency measurement difficult, but in
agreement with Mast (1970), Hochfeld (1973), and Evans and Zhao (1993), the latency was not much longer than that to ipsilateral excitation: the onset of inhibition was <7 msec, and the effect was fully developed within 20-30 msec. The short onset latency leaves little room in terms of number of synapses and conduction speeds involved. In
the final section we argue that the Oc cells play a key
role in the contralateral inhibition, as they do in the ipsilateral inhibition.
The pivotal role of Oc cells
Oc response patterns were first described by Godfrey
et al. (1975a,b) ("on-type L" category), and were later tied to a
specific morphological class (Rhode and Smith, 1986a; Smith and Rhode, 1989). These and other studies drew attention to the remarkable properties of these cells, including a wide dynamic range, broad frequency tuning, excellent phase-locking to envelopes and
low-frequency tones, and their likely inhibitory nature. The response
of these cells to broadband noise is higher than that to tones (Winter and Palmer, 1995; Joris, 1998), presumably because of a requirement of
coincident input activity across a range of CFs (Winter and Palmer,
1995; Palmer et al., 1996). Oc cells have been proposed to
be the "wide-band inhibitor" needed to explain the spectral nonlinear behavior of type IV cells (Nelken and Young, 1994; Winter and
Palmer, 1995).
We found that Oc cells show excellent envelope
phase-locking over a wide range of SPLs and fm
values, in agreement with Rhode and Greenberg (1994). As already
mentioned, the temporal properties of these cells are consistent with
their hypothesized inhibitory influence on type II and III+IV cells.
Moreover, the binaural effects in type III+IV cells, in combination
with previous tracing, immunocytochemical, and pharmacological
observations (Pirsig et al., 1968; Cant and Gaston, 1982; Wenthold,
1987; Osen et al., 1990; Kolston et al., 1992; Evans and Zhao, 1993;
Schofield and Cant, 1996), are consistent with the hypothesis that
Oc cells also provide glycinergic contralateral
inhibition of type III+IV cells. This inhibition is weak to tones and
strong to broadband noise, and has a short latencyproperties also
found in Oc cells. In addition, we have preliminary direct
evidence (our unpublished results) from intra-axonal labeling studies
that Oc cells constitute the commissure between the
cochlear nuclei.
One puzzling observation, if indeed the Oc cells directly
supply the contralateral inhibition, is the near-absence of envelope phase-locking. Possibly this reflects distal placement of the inhibitory input on the dendritic tree of fusiform cells (Smith and
Rhode, 1985), as also supported by the observation that the inhibition is not able to overcome ipsilateral excitation (Fig. 9D) (Vu and Krasne, 1992
Top
Abstract
Introduction
