1Department of Otolaryngology, West Virginia University School of Medicine, Morgantown, West Virginia 26506-9200; 2Department of Biomedical Engineering and Center for Hearing Sciences, Johns Hopkins University, Baltimore, Maryland 21205; and 3Department of Physiology, Hebrew University-Hadassah Medical School and the Interdisciplinary Center for Neural Computations, Hebrew University, Jerusalem, Israel
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ABSTRACT |
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Spirou, George A., Kevin A. Davis, Israel Nelken, and Eric D. Young. Spectral Integration by Type II Interneurons in Dorsal Cochlear Nucleus. J. Neurophysiol. 82: 648-663, 1999. The type II unit is a prominent inhibitory interneuron in the dorsal cochlear nucleus (DCN), most likely recorded from vertical cells. Type II units are characterized by low rates of spontaneous activity, weak responses to broadband noise, and vigorous, narrowly tuned responses to tones. The weak responses of type II units to broadband stimuli are unusual for neurons in the lower auditory system and suggest that these units receive strong inhibitory inputs, most likely from onset-C neurons of the ventral cochlear nucleus. The question of the definition of type II units is considered here; the characteristics listed in the preceding text define a homogeneous type II group, but the boundary between this group and other low spontaneous rate neurons in DCN (type I/III units) is not yet clear. Type II units in decerebrate cats were studied using a two-tone paradigm to map inhibitory responses to tones and using noisebands of varying width to study the inhibitory processes evoked by broadband stimuli. Iontophoresis of bicuculline and strychnine and comparisons of two-tone responses between type II units and auditory nerve fibers were used to differentiate inhibitory processes occurring near the cell from two-tone suppression in the cochlea. For type II units, a significant inhibitory region is always seen with two-tone stimuli; the bandwidth of this region corresponds roughly to the previously reported excitatory bandwidth of onset-C neurons. Bandwidth widening experiments with noisebands show a monotonic decline in response as the bandwidth increases; these data are interpreted as revealing strong inhibitory inputs with properties more like onset-C neurons than any other response type in the lower auditory system. Consistent with these properties, iontophoresis of inhibitory antagonists produces a large increase in discharge rate to broadband noise, making tone and noise responses nearly equal.
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INTRODUCTION |
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Neurons of the dorsal cochlear nucleus (DCN) are
notable for the complexity of their response maps, especially their
prominent inhibitory inputs (Evans and Nelson 1973;
Greenwood and Maruyama 1965
; Young and Brownell
1976
). Many of the sound-evoked responses of the principal
cells of the DCN, especially those classified physiologically as type
IV units, are attributable to activity in a particular inhibitory
interneuron called a type II unit (Voigt and Young 1980
,
1990
). The type II unit exhibits a unique set of physiological
responses, principally defined by its near zero spontaneous activity
and its robust response to tonal stimuli relative to broadband stimuli
(Davis et al. 1996
; Joris 1998
; Young and Brownell 1976
; Young and Voigt
1982
).
The most likely anatomic correlate of type II units is the vertical, or
tuberculoventral, cell in DCN. Vertical cells are located in the deep
DCN, in a thick band beneath the pyramidal cell layer (Lorente
de Nó 1981; Zhang and Oertel 1993b
). They are characterized by small somata, vertically oriented dendrites, and
immunocytochemical staining for the inhibitory neurotransmitter glycine
(Kolston et al. 1992
; Osen et al. 1990
;
Saint Marie et al. 1991
). Vertical cell axons project
within their isofrequency sheet in DCN and also send a collateral to
the ventral cochlear nucleus (VCN) (Lorente de Nó
1981
; Zhang and Oertel 1993b
). The projections
in DCN make inhibitory contacts on principal cells, as inferred from
the patterns of inhibitory postsynaptic potentials (IPSPs) evoked by
stimulation of the auditory nerve (Zhang and Oertel 1993a
,
1994
). In addition, both bushy and multipolar cells of the VCN
have been shown to receive a glycinergic input from the region
containing vertical cells in the DCN (Wickesberg and Oertel
1990
), so that inhibitory effects from vertical cells are probably also important in VCN. Although DCN structure varies considerably across species, the vertical cell system seems to be a
stable feature of its organization (e.g., cat, Osen et al. 1990
; guinea pig, Kolston et al. 1992
;
Saint Marie et al. 1991
, bat, Kemmer and Vater
1997
; and baboon, Moore et al. 1996
), suggesting that this inhibitory system is a fundamental part of signal processing in the mammalian cochlear nucleus.
The correspondence between type II units and vertical cells is based on
three lines of evidence: the first is their common identity as
inhibitory neurons (Davis and Voigt 1997; Voigt
and Young 1980
, 1990
); the second is the fact that type II
units do not project out of the nucleus through the dorsal acoustic
stria (Joris 1998
; Young 1980
) but can be
antidromically activated from the VCN (Young 1980
); the
third is the location of type II recording sites in the deep DCN in the
general location of vertical cells (Ding and Voigt 1997
;
Voigt and Young 1990
; Young and Voigt
1982
; this paper). Attempts to identify type II units by dye
filling have given mixed results (Ding et al. 1994
;
Joris and Smith 1995
; Rhode 1999
) but are
generally consistent with the type II-vertical cell link.
The weak responses of type II units to broadband noise has led to the
hypotheses that they are themselves the targets of substantial inhibitory input and that this input is more responsive to broadband than narrow band sounds (Spirou and Young 1991;
Young and Voigt 1982
). A similar inhibitory input is
needed to account for certain properties of DCN principal cells
(Nelken and Young 1994
, 1997
), and it is parsimonious to
assume that the two inhibitory inputs come from the same neuron, the
so-called wideband inhibitor. Neurons with properties appropriate to
the wideband inhibitor, called onset-C units, have been recorded in the
VCN (Joris 1998
; Smith and Rhode 1989
;
Winter and Palmer 1995
). The temporal properties of
onset-C units have been shown to be appropriate for an inhibitory input
to both type II and type IV neurons in DCN (Joris and Smith 1998
). However, the spectral integration properties of type II units and onset-C units have not been critically compared as a test of
the hypothesized inhibitory relationship.
In this paper, the spectral integration properties of type II units are
described and compared with those of onset-C units, as reported by
Palmer and colleagues (Jiang et al. 1996; Palmer et al. 1996
). First, the definition of type II units is
considered, in relation to a similar group of units, called type I/III.
It is shown that a homogeneous type II group can be defined using conservative criteria, but that a definitive separation of the two unit
types is not possible using the physiological measures that have been
employed. Type II units that fit the conservative definition are shown
to be more strongly inhibited by stimuli as the bandwidth is increased;
this property parallels the increase in response observed in onset-C
units as bandwidth increases. The broadband inhibition of type II units
is shown to be blocked by either strychnine or bicuculline; with both
antagonists, type II units give more nearly equal tone and noise
responses. The results are generally consistent with an inhibitory
input to type II neurons from onset-C neurons, or from essentially
identical neurons.
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METHODS |
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Animal preparation
The data in this paper were collected along with other data that
have been published previously (Davis and Young 1997;
Nelken and Young 1994
; Shofner and Young
1985
; Spirou and Young 1991
; Spirou et
al. 1993
; Sydorenko 1992
; Voigt and Young
1990
; Young et al. 1995
); some data from
unpublished experiments on iontophoresis and two-tone suppression in
the auditory nerve also are included. The preparation and experimental
methods were essentially identical across those studies. All protocols
were approved by the Animal Care and Use Committee at the Johns Hopkins University.
Cats with clean external ears were decerebrated under ketamine anesthesia, usually after receiving xylazine as a tranquilizer. Atropine was given to control mucous secretion. No additional anesthetic was given after the decerebration. A tracheal cannula was inserted to maintain a clear airway, and the bulla was vented with a length of small-bore polyethylene tubing. The cats' temperatures were maintained between 36 and 38°C, and lactated Ringer solution was given regularly to preserve fluid volume. Some animals were respired artificially to maintain adequate respiration or with a pneumothorax to increase the stability of recording. These animals were paralyzed with gallamine triethiodide and maintained at 4% end-tidal CO2.
The DCN was exposed in one of two ways: a hole was drilled through the
bone lateral to the foramen magnum (Young and Brownell 1976) or the cerebellum was aspirated and the DCN was
approached from the contralateral side (Spirou et al.
1993
). In the first approach, the electrode is placed directly
on the surface and travels perpendicular to the DCN's layers but
roughly parallel to an isofrequency lamina. In the second approach, the
electrode travels parallel to the pyramidal cell layer and
perpendicular to the DCN's isofrequency laminae.
Single neurons were recorded using platinum-iridium electrodes. In some
experiments, a multibarrel glass electrode was piggybacked on the metal
electrode to allow iontophoresis of glycine or
GABAA antagonists in the vicinity of the
recording site (similar to Havey and Caspary 1980). One
barrel was filled with strychnine hydrochloride, a second was filled
with bicuculline methiodide (each 10 mM, pH 3.5-4.0), and the third
barrel was filled with pH-balanced buffer (potassium hydrogen
phthalate, pH 4.0). A constant current generator passed
20 nA between
each drug barrel and the buffer barrel as a retention current and +50
nA to eject the drug. In these experiments, control data were taken
first; then the iontophoresis was turned on and test data were taken
with the current on; then the ionophoresis was turned off and data were taken during recovery to control conditions. In all cases where units
were held long enough (4/8), complete recovery from both strychnine and
bicuculline was observed.
In one experiment, the auditory nerve was exposed by retraction of the cerebellum after the decerebration. Glass micropipettes were used to record from auditory nerve fibers.
Acoustic stimuli and experimental protocol
Sound was delivered using a closed system connected to the
ipsilateral ear through an earbar. The system was calibrated in situ
using a calibrated probe tube placed ~2 mm from the eardrum. Examples
of the acoustic calibration have been shown previously (Rice et
al. 1995; Spirou and Young 1991
). The
calibration is flat with fluctuations of <10 dB at frequencies
30-40 kHz.
When a unit was isolated, it was characterized based on its responses
to tones at best frequency (BF) and to broadband noise. Rate versus
level functions were constructed for BF tones and broadband noise by
presenting 200-ms stimulus bursts once per second over an 80- to 100-dB
range of levels. Sound level was changed in 1-dB steps and each level
was presented once. These data were used to define the neuron's
response type using the criteria described previously (Young
1984) and elaborated in this paper. Additional studies varied
with the goals of the particular experiment. For many units, response
maps were constructed by recording the responses to 200-ms tone bursts
presented over a range of frequencies (generally 2-5 octaves
interpolated logarithmically to 100 points) and a range of sound levels
(generally 40-70 dB in 8- to 10-dB steps). Again, each
frequency/sound-level combination was presented once. Response maps
also were taken in the presence of a second tone, a fixed BF tone of
3-8 dB above threshold, which served to produce a steady level of
background activity. This two-tone paradigm allowed inhibitory
responses to be seen in the absence of spontaneous activity.
For some units, responses to noisebands of varying bandwidth were
obtained. The noisebands were generated by multiplying a low-pass
filtered noise (bandwidth fl) by a
tone of frequency f0, which results in
a noiseband of width 2fl centered at
f0. To eliminate temporal
fluctuations, two independent low-pass filtered noises were multiplied
by quadrature tones (i.e., tones of the same frequency 90° out of
phase) and added (Spirou and Young 1991). In later
experiments, noisebands were generated digitally by inverse Fourier
transforming the desired spectrum and playing the resulting signal
through a 16-bit D/A converter (Nelken and Young 1997
).
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RESULTS |
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Properties of type II units
Data from a total of 201 units are included in this paper. Because type II units are difficult to isolate, recording times are generally not long and few units were studied with more than one or two different stimulus types. Most data are from a subset of 41 type II units that were studied with two or more stimulus paradigms.
Figure 1, A-C, shows examples
of type II units. These units have no spontaneous activity, narrow
V-shaped tuning, strong responses to tones with characteristically
nonmonotonic rate behavior at BF, and weak or no response to noise.
Figure 1A shows a typical response map for a type II unit.
It consists of a V-shaped portion at low sound levels and a broad tail
extending to low frequencies at high sound levels. The tuning of type
II units is similar to that of auditory nerve fibers at 10 dB re
threshold but is somewhat narrower, for units with BF >1 kHz, at 40 dB
above threshold (Davis et al. 1996; Young and
Voigt 1982
); moreover, the low-frequency tail of type II units
occurs at sound levels >60 dB re threshold, as opposed to 40-60 dB in
auditory nerve fibers (Young and Voigt 1982
).
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Figure 1, B and C, shows plots of discharge
rate versus sound level (rate-level curves) for two type II units
(A and B are the same unit). These data are
typical of type II units in that they show nonmonotonic responses to BF
tones () and weak responses to broadband noise (- - -). Two
measures of type II characteristics are shown. The degree of
nonmonotonicity is characterized as the slope of a line fit (least
squares) to the rate-level function at sound levels above the first
inflection point in the curve. The fit was done only over the range of
levels (
20 dB) showing a roughly linear behavior. The slopes of many
type II units change at the highest levels (Fig. 1C), and
these levels were not included in the fit. The second measure is the
relative noise response, defined as the ratio of the maximum noise
response (a in Fig. 1C) to the maximum tone response (b in
Fig. 1C).
In addition to type IIs, the DCN contains other units without
spontaneous activity; examples are shown in Fig. 1, D and
E. These units have stronger responses to noise than type II
units and show saturating (Fig. 1D) or monotonic (except for
noise fluctuations; Fig. 1E) rate-level functions for BF
tones. Units with low spontaneous rates and strong responses to noise
have been classified as type I/III (Young 1984).
The examples of type II and I/III units in Fig. 1 are typical in that almost all low spontaneous rate DCN units respond vigorously to BF tones; the variability in their relative noise response comes mainly from differences in the strength of the noise response.
The definitions given in the preceding text do not provide quantitative
criteria for distinguishing between type II and type I/III units.
Figure 2A shows the
distribution of low spontaneous rate DCN units along two dimensions,
which often are used in the definition of type II units (Davis
et al. 1996; Young and Voigt 1982
). The ordinate
shows the degree of nonmonotonicity, defined as the slope of lines like
those shown in Fig. 1, normalized by the maximum discharge rate; the
abscissa shows the relative noise response, defined as the ratio a/b in
Fig. 1C. Type II units occupy the bottom left
part of Fig. 2A, reflecting their weak noise responses and
nonmonotonic BF tone rate-level functions (negative slopes). Type I/III
units are in the top right part of this panel. There is a
general correlation between weak noise responses and nonmonotonic BF
rate-level curves (r = 0.42, P
0.001).
However, there is no evidence of a division of the low spontaneous rate
units into two qualitatively different groups.
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Previously, type II units have been defined as having relative noise
response <0.3-0.36 (Davis et al. 1996; Shofner
and Young 1985
; Young 1984
), although this
criterion was relaxed in one study (Sydorenko 1992
).
Figure 2B shows a histogram of relative noise response
obtained from the population of Fig. 2A. These data do not
form an obvious bimodal distribution, although there is a dip in the
distribution at the 0.35-0.4 bin, which corresponds to the previously
used criterion. The vertical dashed line in Fig. 2A is
placed at a relative noise response of 0.35. Units to the
left of this line all have nonmonotonic BF rate-level curves as well as weak noise responses. Units to the right of this
line form a mixed population with both monotonic and nonmonotonic
rate-level curves. Thus a conservative definition of type II units
consists of units in the box in Fig. 2A, bottom left, as
defined by the dashed lines (see also Davis et al.
1996
).
Given the evidence reviewed in the INTRODUCTION that type
II units are recorded from vertical cells, it is interesting to know to
what extent this conservative definition captures units with the
properties expected of vertical cells. The shaded boxes in Fig. 2,
A and B, are units that were activated
antidromically from the anteroventral cochlear nucleus (AVCN)
(Young 1980). Because vertical cells are the only DCN
neurons known to project an axon into the principal cell areas of the
VCN, these neurons are by definition vertical cells. Data on these
units are incomplete because they were characterized manually in some
cases; however, in all cases where data were taken, the BF rate-level
functions were nonmonotonic (3 cases) and the relative noise responses
were <0.35 (4 cases). Thus units antidromically activated from the VCN
all fit the conservative type II definition.
The filled black symbols in Fig. 2, A and
B, show type II units that have inhibitory-type
cross-correlations with type IV units (Sydorenko 1992;
Voigt and Young 1980
, 1990
). Most of these (13/16) are
within the conservative definition of type II, although there are three
cases with relative noise responses outside the dashed-line box. The
other properties of those three units were typical of type II units,
low spontaneous rates, and nonmonotonic BF rate-level functions. Those
three units show that the conservative definition excludes some units
that share important properties with type II units and could be
considered to be members of an extended type II family. However,
because most units with inhibitory correlations fit within the
conservative definition and because these units scatter throughout the
boxed region, the conservative definition probably captures most type
IIs and mostly type IIs.
A final property that may be useful in distinguishing type II units
from other response types is the degree of activation by somatosensory
inputs. Type II units within the dashed-line box of Fig.
2A are inhibited weakly by electrical stimulation of the
somatosensory dorsal column or spinal trigeminal nuclei (Young
et al. 1995). By contrast, units with characteristics like the
examples in Fig. 1E are sometimes strongly excited by
somatosensory stimulation. Units of this type are marked by stars and
are located in Fig. 2A, top right. These units have
strong noise responses and monotonic BF tone rate-level curves and are
clearly different from type IIs.
Figure 2C shows a histogram of the depths of the
recording sites of 49 type II units, with characteristics that meet the
conservative definition. The recording depths were determined from
histological reconstructions of recording tracks and are expressed as
the distance, perpendicular to the free surface of the DCN, from the
center of the pyramidal cell layer. Most type II recording sites are between 0 and 1 mm below the pyramidal cell layer, which is consistent with the location of the vertical cells in DCN (Lorente de
Nó 1981; Saint Marie et al. 1991
;
Zhang and Oertel 1993b
).
The evidence in Fig. 2 supports the idea of a type II unit class that has low spontaneous rate, strong but nonmonotonic responses to BF tones, and (usually) weak responses to noise; at least some of these units are recorded from DCN vertical cells and are inhibitory interneurons. At the same time, there are other units, called type I/III, that have different properties. Although it is not possible to draw a definitive boundary between the two types using the criteria considered, nonmonotonic units with relative noise responses less than ~0.35 appear to form a group with uniform type II properties. This group of units forms a proper or conservative type II group but may exclude the tail of the type II distribution. In the remainder of this paper, we describe mostly units with properties that place them within the conservative type II group; in some cases, results are shown also for units outside the conservative type II group to illustrate the similarities in their properties.
Two-tone response maps have inhibitory regions
The weak responses of type II units to noise and the
nonmonotonicity of their BF rate-level curves suggest that these units receive substantial inhibitory input (Young and Voigt
1982). Figure 3 shows two-tone
response maps of four type II units. These maps are in the same format
as Fig. 1A, except that the horizontal lines are the rate
produced by a fixed-level BF tone and the plots show the deviation from
that rate produced by a variable tone. Excitatory areas are filled with
black and inhibitory areas are shaded. Note that the term
"inhibitory" is used here in a functional sense, meaning rate
reduction. Inhibitory responses could be produced by actual inhibition
in the DCN or by cochlear two-tone suppression (Sachs and Kiang
1968
). Evidence regarding the relative amount of true
inhibition versus cochlear suppression is offered in the next section.
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The typical type II response map consists of a narrow excitatory region centered on BF and flanked by both upper and lower inhibitory sidebands (UISB, LISB). The ISBs often appear to reflect a single inhibitory region centered on BF with a bandwidth wider than that of the excitatory input (Fig. 3, C and D). In other cases, the BF of the inhibition appears to be centered away from the type II BF (Fig. 3, A and B). For most type II units, the UISB has a lower threshold and is more prominent than the LISB at low to medium levels. Generally at least one sideband has a threshold very similar to, or even lower than, the BF excitatory threshold.
The extent of the ISBs was revealed by measuring the bandwidths, in
kilohertz, of both sidebands at 40 dB above BF threshold. Figure
4A shows the UISB and LISB
bandwidths plotted versus BF along with the total bandwidth of the
inhibitory region, assuming that it is a single V-shaped area.
Bandwidths increase with BF, although the growth is less than a
one-for-one increase; the slopes of regression lines to the three sets
of data in the log-log plot in Fig. 4 are 0.69 (LISB), 0.29 (UISB), and
0.36 (total). Most of the total bandwidth, measured linearly in hertz,
is in the UISB, as can be seen by the similarity of the total and UISB
bandwidths in Fig. 4A. Figure 4B shows the UISB
and LISB bandwidths in logarithmic terms, as the distance in octaves
from BF to the lower side of the LISB or to the upper side of the UISB.
These octave distances are smaller for higher BFs, which is the same
effect as the slower-than-linear growth of bandwidth in Fig.
4A. The upper and lower sidebands are roughly the same
width, in logarithmic terms. However the linear measure of width in
Fig. 4A may be more relevant when considering responses to
noise signals, in which there is a fixed power per linear bandwidth. It
is evident from Fig. 4A that the total noise power in the
UISB is significantly larger than the noise power in the LISB for a
broadband noise with constant spectrum level.
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Two-tone suppression or neural inhibition?
Because the type II response maps were measured using a two-tone paradigm, the inhibitory responses in Fig. 3 could be produced either by cochlear two-tone suppression or direct inhibition in the cochlear nucleus. The relative contributions of these two sources were estimated in two ways: by determining the amount of suppression seen in auditory-nerve fibers using the same stimulus paradigm and by blocking local inhibition with iontophoretic application of inhibitory neurotransmitter antagonists.
The two-tone response map paradigm was presented to auditory-nerve
fibers in one animal. Fifty-four fibers were isolated long enough to
measure BF and spontaneous rate (SR); the proportions of low, medium,
and high SR fibers was roughly the same as is usually found
(Liberman 1978) (in our data: 8/54 low SR, 15.4%; 13/54
medium SR, 25%; 31/54 high SR, 59.6%). Twenty-one auditory-nerve fibers were held long enough to generate two-tone response maps.
Typical two-tone response maps for auditory nerve fibers are shown in
Fig. 5; the shaded regions show two-tone
suppression. In most cases (15/19 with two uncertain cases), below-BF
suppression was not encountered in auditory-nerve fibers. Two-tone
suppression below BF has been documented in auditory nerve fibers
(Rhode and Greenberg 1994; Sachs and Kiang
1968
; Schmiedt 1982
), but it occurs at higher
stimulus levels than were used routinely here. Suppression areas were
seen in almost all fibers at frequencies above BF (20/21), as in these
two examples.
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The thresholds for an inhibitory or suppressive response were compared
between auditory nerve fibers and type II units. Figure 6 shows the distribution of these
thresholds in auditory nerve fibers (A-D) and type II units
(E and F). Over the range of BFs included in
these data, the sideband thresholds vary systematically with BF (not
shown). These BF trends were removed from the data by subtracting the
BF trend line determined for the type II units' sidebands; as a
result, the thresholds in Fig. 6 are shown relative to the average type
II threshold at the same BF. Actual and extrapolated thresholds are
shown ( and
),
computed as described in the figure caption, as is the highest sound
level presented in cases (
) where no suppression or
inhibitory response was observed . Consistent with Fig. 5, there are
few estimates of auditory-nerve suppression thresholds for frequencies
below BF (Fig. 6, A and C). In contrast, all type
II units had LISBs and the median type II threshold (Fig. 6E,
) is below the lowest lower-bound values for the
auditory nerve fibers.
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Both auditory nerve fibers and type II units showed inhibitory responses for frequencies above BF (except for 1 auditory nerve fiber; Fig. 6, B, D, and F). Type II UISB thresholds (Fig. 6F) overlapped considerably with auditory-nerve suppression thresholds, especially for low and medium SR auditory-nerve fibers (Fig. 6D). In fact, the medians of the threshold distributions for low and medium SR auditory-nerve and type II units are not significantly different (P > 0.3, rank-sum test).
These threshold results suggest that at low to moderate sound levels, type II LISBs represent inhibitory processes in the DCN and cannot be explained by cochlear suppression. However, many UISBs could reflect two-tone suppression, especially of low and medium SR auditory-nerve fibers, if such fibers are the predominant source of the excitatory inputs to type II units.
Application of antagonists to inhibitory neurotransmitters while presenting the two-tone stimulus paradigm provides a direct test of inhibition. Figure 7 shows two-tone response maps for two type II units in control conditions (left) and during iontophoresis of either strychnine (Fig. 7B) or bicuculline (Fig. 7D). The control response map was repeated for comparison in the right column (- - - and · · ·). The inhibitory antagonists had the general effect of increasing the response to the low level BF tone, evident as an increase in the background rate shown by the horizontal lines. In fact, for all cases except the one shown in Fig. 7B (7/8 cases), there was an increase in rate to BF tones at all levels in the presence of strychnine or bicuculline. At all stimulus levels, except the highest level in Fig. 7D, the LISB was eliminated by drug application, suggesting that it results from neural inhibition. By contrast, the UISB was reduced in bandwidth but inhibitory responses to the second tone remained. The bandwidth changes in the UISB were small but reliable; the bandwidths were measured by determining the frequencies at which inhibition was halfway between the background rate and the minimum rate in the sideband. At 40 dB above threshold, the UISB bandwidth was reduced by an average of 28% (range 19-39%, n = 4) by strychnine and 40% (range 20-54%, n = 3) by bicuculline. This result suggests that the UISB consists of a mixture of inhibition and cochlear suppression.
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The results shown in Fig. 7 are typical; essentially identical changes in two-tone response maps were obtained in four cases with strychnine and three cases with bicuculline. The effects of applying inhibitory neurotransmitter antagonists are thus consistent with the inferences drawn from the threshold data in Fig. 6.
Iontophoresis shows that inhibition by noise is strong
The weak responses of type II units to noise suggests that their inhibitory input is somehow stronger for noise than for tones. Pharmacological blockade of inhibitory neurotransmitters supports this hypothesis. Figure 8A shows rate-level curves for BF tones and noise before and during iontophoresis of strychnine or bicuculline. Control responses are shown by the light solid lines and responses during inhibitory blockade are shown by the dashed (bicuculline) and heavy solid (strychnine) lines. For both tones and noise there was a substantial increase in rate when either inhibitory antagonist was applied. However, the increase in noise response was much larger than the increase in tone response. During strychnine application, the saturation discharge rates were approximately the same for tones and noise even though the noise response was essentially zero in the absence of inhibitory blockade. For bicuculline, the effects were similar, although not as large. For the type I/III unit shown in Fig. 8B, application of strychnine also produced an increase in response, but in this case, the relative noise response was approximately the same (0.6) before and during strychnine application. The examples in Fig. 8, A and B, are typical in that inhibitory blockade did not produce spontaneous activity in any of the cases tested (6 tested with both antagonists, 2 others tested with 1 blocker only).
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Figure 8C shows a comparison of relative noise response before (abscissa) and during (ordinate) application of inhibitory antagonist for all the units tested. Type II units are the points to the left of the vertical dashed line, i.e., the units with relative noise response <0.35 before iontophoresis. In all cases, the relative noise response increased dramatically with inhibitory blockade; the effects were larger for strychnine than for bicuculline. Type I/III units are the points to the right of the dashed line. For two of these cases, there was no increase in relative noise response with strychnine, although there was an increase in discharge rate (Fig. 8B is an example); in the remaining cases, the relative noise response increased. Figure 8C shows that type II units, and to a lesser extent type I/III units, receive glycinergic and GABAergic inputs that are much more effective for broadband noise stimuli than for tones.
Noiseband widening suggests strong inhibitory inputs
The frequency extent of the inhibitory input to type II units can be examined using noisebands of varying bandwidth. Figure 9 shows examples of rate-level curves for BF tones, noisebands, and broadband noise for two type II units. The noisebands were centered arithmetically at BF, and the bandwidths are marked on the curves. Sound level is plotted on the abscissas as total stimulus power. As a result, the curves should shift to the right as the stimulus bandwidth exceeds the integrating bandwidth of the unit; inhibitory effects should show up as reductions in discharge rate. Generally the responses for the narrowest noisebands tested are similar to the BF tone responses at the same stimulus power. These two units are typical of most units in that the rate to the narrowest noiseband is somewhat less than the rate to the tone. For all units examined (15), there was a monotonic decline in the response rate as the bandwidth increased. This response profile is strongly suggestive of an inhibitory input that is recruited over a wide range of stimulus bandwidths.
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Figure 10A shows a population plot of the maximum discharge rate across sound level versus bandwidth for data like those in Fig. 9. Data are shown for 14 type II units, and 1 unit that had a noise response outside the conservative type II definition. Maximum rates to BF tones and broadband noise are shown at the left and right extremes of the abscissa. This plot shows that the steady decline in response rate with stimulus bandwidth illustrated in Fig. 9 occurs in the whole population. However, there is considerable variability across the population in the relative noise responsive and the effects of bandwidth. These effects are shown more clearly in the normalized plot of Fig. 10B, where maximum rate is plotted relative to BF tone rate and bandwidth is expressed relative to BF. The variability is only partly reduced; the relative bandwidth at which units' responses are reduced by 50%, for example, varies over an order of magnitude.
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Figure 10B shows that noise affects type II units over a very wide bandwidth. In most units, there is a decline in rate between the widest noiseband used and broadband noise. For example, in seven units rate declined by an average of 44% (range 3-75%) between a noiseband approximately twice as wide as BF (range 1.8-2.3) and broadband noise. That is, the inhibitory inputs to these units integrate energy over a frequency range extending more than an octave above BF.
Figure 11 shows a comparison of the
inhibitory effects of tones and noise. Data are shown from three type
II units in which both a two-tone response map and noiseband responses
were obtained. Response rate versus tone frequency is shown (solid
lines) for the two-tone paradigm with the variable tone at 50 dB
above threshold; the fixed tone was, as usual, near threshold and
produced the rate shown by the horizontal line. Tone responses are
excitatory when the rate is above the horizontal line. The dotted
vertical lines show the limits of the excitatory region as inferred
from these tone responses. The symbols and dashed lines show rates in
response to noisebands of various bandwidths. Each point is plotted
twice, once at the frequency of the lower edge and again at the
frequency of the upper edge of the noiseband. The noiseband levels were
chosen to keep the spectrum level constant as bandwidth changed at the
level at which the narrowest noiseband had the same total power as a BF
tone. Notice that as noise energy was added, the discharge rate
decreased, indicating an inhibitory effect. The rate decrease began at
the narrowest bandwidth tested, even though those bandwidths were well
within the unit's excitatory response range as determined by tones.
Thus energy at frequencies within the excitatory area causes a rate
increase when presented as a tone, but a rate decrease when added to a
noiseband. This result is consistent with the iontophoresis data in
suggesting that the inhibitory inputs to type II units are more
strongly activated by noise than by tones.
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DISCUSSION |
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Type II and type I/III units
The type II response type first was defined on the basis of its
low response to broadband noise (Young and Voigt 1982).
Type IIs are the only units in the cochlear nucleus that have this property. However, a more important insight was the association of type
II units with an inhibitory interneuron in DCN. The first evidence for
this relationship was the finding of inhibitory-type cross-correlation
between type II units and the response types associated with DCN
principal cells (Voigt and Young 1980
). There are
several inhibitory interneurons in DCN (Osen et al.
1990
), but the evidence reviewed in the Introduction from
antidromic stimulation, from recording in the dorsal acoustic stria,
from the locations of type II recording sites, and from intracellular dye filling points to the vertical cell as the source of type II
recordings. Because response types are most useful when they can be
related to functional and anatomic entities, we suggest that type II
should be thought of as a response type given by vertical cells. That
assumption will be made in the remainder of this discussion.
The data in Figs. 1 and 2 show that type II units can be defined with a
reasonably homogeneous set of properties including low spontaneous
activity, low relative noise response, vigorous tone responses with a
characteristic nonmonotonicity at high sound levels, and narrowly tuned
response maps. A conservative definition of type II can be given based
on these properties, but some units that might be called type II lie
outside the conservative boundaries where they are apparently
intermingled with type I/III units. The problems of defining unit types
on the basis of responses to sound have been discussed (Joris
1998), and those problems apply here. In particular, it is not
possible to draw an absolute boundary between type II and type I/III
units on the basis of the existing data because of overlap of the two
groups in plots like Fig. 2A. Additional measures, such as
width of dynamic range (Davis et al. 1996
) and PST
histogram shape (Shofner and Young 1985
) were
considered, but found not to be helpful. Despite the lack of a clear
boundary between types II and I/III, it nevertheless seems clear that
there is more than one neuron type involved, and it also seems safe to
assume that the conservative definition in Fig. 2A defines a
homogeneous, but not necessarily inclusive, set of type II neurons.
In intracellular recordings in gerbil (Ding and Voigt
1997), type II and type I/III units are generally similar,
although they show some differences in action potential parameters and in the prevalence of hyperpolarizing responses to off-BF tones (type II
units showed them, type I/III units usually did not). The latter
finding is consistent with the inference from Fig. 2A that
type II units show stronger effects of inhibition (i.e., weak noise
responses and nonmonotonic tone responses) than do type I/III units.
These results suggest that the main difference between the two unit
types might be the amount and strength of inhibitory input.
The anatomic identity of type I/III units is a matter of question. Type
I/III responses have been recorded from a few identified pyramidal
cells (Ding and Voigt 1999), although these cells are much more likely to be type III or IV (Ding and Voigt
1999
; Joris 1998
; Rhode et al.
1983
; Young 1980
). One possibility, suggested by
the general similarity of type I/III and type II responses and by the
fact that they appear to form a continuum in plots like Fig.
2A, is that they are recorded from different subpopulations of vertical cells. Some heterogeneity exists within the vertical cell
population; for example, vertical cells located more deeply in the DCN
have greater tendency to form VCN projections and a minority of cells
have axonal arborizations only in the deep DCN (Lorente de
Nó 1981
). Immunocytochemistry reveals variations of
intensity of glycine immunolabeling among small cells in deep DCN and
about one-third of the cells colocalize GABA immunoreactivity in cat
(Osen et al. 1990
). It may be that the position of a
cell in deep DCN determines its synaptic influences and type I/III units are those receiving less broadband inhibitory input. The question
of the identity of type I/III units can only be settled by further research.
It is important to recognize that type II units should be defined as
having a conjunction of properties: low SR, weak response to noise, and
vigorous, narrowly tuned, slightly nonmonotonic response to tones.
Attempts to construct a tree diagram for classifying neurons in DCN
(Joris 1998) inevitably lead to separate decisions on
these classification variables. The result, as pointed out by Joris in
his paper, is that obvious misclassifications occur. For example, the
degree of nonmonotonicity and the spontaneous rate of type II units
overlap with other response types. In classifying type II units,
therefore, simultaneous consideration should be given to all aspects of
the unit's response.
Sources of excitatory input to type II units
An interesting observation is that application of strychnine and
bicuculline did not increase SR in type II units. One interpretation of
this result is that the excitatory input to these units is from a
source with little or no spontaneous activity. Vertical cells receive
monosynaptic excitatory input from auditory nerve fibers (Oertel
and Wu 1989; Zhang and Oertel 1993b
). Taken
together, these two results suggest that low SR auditory nerve fibers
may form the major excitatory input to type II cells. If true, this hypothesis also could explain the finding that type II units have consistently higher thresholds than DCN principal cells (Young and Brownell 1976
) because low SR auditory nerve fibers also
have elevated thresholds relative to the lowest threshold auditory nerve fibers (Liberman 1978
). However, patterns of
auditory nerve innervation of the DCN are most consistent with high SR
fiber innervation of vertical cell somata and low SR fiber innervation of dendrites (Liberman 1993
). In that case, the low
spontaneous rates and high sound thresholds of type II units might be
caused by a high intrinsic electrical threshold (Hancock et al.
1997
); this is consistent with the responses of vertical cells
to intracellular current injection (Ding and Voigt 1997
;
Zhang and Oertel 1993b
).
Vertical cells receive polysynaptic excitatory postsynaptic potentials
(EPSPs) after stimulation of the auditory nerve root in slice
preparations (Zhang and Oertel 1993b). EPSPs also are evoked from glutamate stimulation of a tonotopically appropriate region
of the VCN. These polysynaptic inputs could be from T-stellate cells of
the VCN, which make terminals with excitatory morphology (Smith
and Rhode 1989
) and project an axon collateral to the DCN (Oertel et al. 1990
). The role of T-stellate excitatory
terminals in DCN, relative to those of auditory nerve fibers and
granule cells, remains to be defined, but it is possible that the
excitatory areas of type II units are produced by convergent input from
T-stellate and auditory nerve axons. T-stellate cells give chopper
response patterns to sound (Smith and Rhode 1989
), and
these responses are similar to those of auditory nerve fibers with
regard to many features, such as tuning and rate-level functions
(Blackburn and Sachs 1989
; Bourk 1976
).
However, chopper units also have significant inhibitory inputs
(Blackburn and Sachs 1992
; Rhode and Greenberg 1994
), so the possibility exists that some of the inhibitory
effects seen in type IIs are presynaptic.
Inhibitory inputs to type II units
The results reported in this paper clearly show that type II units
receive inhibitory inputs. To characterize inhibition by tones,
two-tone response maps were used. The apparent inhibition seen in these
maps is generated partly by cochlear two-tone suppression. However, the
comparisons of sideband thresholds (Fig. 6) and the effects of
inhibitory neurotransmitter antagonists (Fig. 7) argue that the
inhibitory responses seen below BF and part of the responses seen above
BF are attributable to neural inhibition. Rhode and Greenberg
(1994) came to the same conclusion based on comparison of a
wider range of properties between auditory nerve and cochlear nucleus.
In fact, when inhibitory antagonists were applied, the bandwidth of the
inhibitory regions in two tone response maps became narrower, so that
the inhibitory bandwidth measurements shown in Fig. 4 are accurate
reflections of the bandwidth of the inhibitory input, with little or no
contamination from cochlear suppression.
Caspary and colleagues (1994) have argued that
inhibitory inputs to neurons in AVCN are centered on the excitatory
tuning curve on the basis of results showing that GABA or glycine
antagonists produce the largest increase in discharge rate for tones at
or near BF. DCN type II units show the same behavior (results to be
shown elsewhere); this effect is evident in Figs. 7 and 8 in the
increase in background discharge rate (the horizontal line) produced by
the fixed tone. Thus it seems reasonable to assume that the inhibitory
inputs to DCN type II units form a single inhibitory area centered at
or near BF.
For noise, the results are also clear. The increase in rate in response to broadband noise following bicuculline or strychnine application (Fig. 8) shows conclusively that the noise stimulus is evoking an inhibitory input. Moreover, the fact that the increase in rate for noise was much larger than for tones (as in Fig. 8, A and C) shows that the inhibitory source gives a stronger response to broadband noise than to tones. Further evidence for this point is the fact that narrow noisebands, the passbands of which are wholly contained within the excitatory tuning curve for tones, cause a reduction in rate relative to the responses to a BF tone and the narrowest noiseband (Fig. 11).
The possible contribution of cochlear suppression to reductions of rate
with noiseband widening should be considered. Auditory nerve responses
to bands of noise arithmetically centered on BF have been studied
(Ruggero 1973; Shalk and Sachs 1980
).
Effects of suppression are seen, but they are weaker than those shown in Figs. 9-11 of this paper. For example, for narrow (200 Hz)
noisebands, the rate in response to the noiseband is the same as the
rate to an equal-energy tone, for all SR groups (Ruggero
1973
; Shalk and Sachs 1980
). By contrast, most
(9/15) type II units gave lower rates to narrow noisebands than to
tones (as in Fig. 9). For wider noisebands, there is a decline in the
saturation rate of rate-level curves in low and medium SR fibers
(Shalk and Sachs 1980
) that is qualitatively similar to
the decrease seen in Fig. 10. The effect is much smaller than that seen
in the type II data; however; in the most extreme example shown by
Shalk and Sachs, the saturation rate for a noiseband of bandwidth equal
to BF was ~0.67 of the saturation rate for a tone. Type II units vary
between 0.1 and 0.6 at the same relative bandwidth (Fig.
10B). Thus the inhibitory effects of noisebands are
substantially stronger in type II units than auditory nerve fibers.
Is the inhibitory input from the wideband inhibitor?
There are several sources of inhibitory terminals within the
cochlear nucleus (Kolston et al. 1992; Osen et
al. 1990
) as well as descending inhibitory inputs from more
central auditory nuclei (Spangler and Warr 1991
). The
possibility that the inhibitory inputs to type II units involve
descending inputs cannot be discounted; however, not enough is known
about such inputs to evaluate their possible contributions, so they
will not be considered further here. Of the inhibitory sources within
the cochlear nucleus, three are known to project axons into the region
of the DCN occupied by the vertical cells. Cartwheel cells of the
superficial DCN immunostain for glycine and sometimes also for GABA
(Gates et al. 1996
; Osen 1990
) and their
axons extend down to the deep DCN (Berrebi and Mugnaini
1991
). However, intracellular recordings from vertical cells do
not show IPSPs with the particular pattern of spontaneous and burst
firing characteristic of cartwheel cells (Golding and Oertel
1997
), so cartwheel cell input can be ruled out.
Second, vertical cells themselves produce significant axonal terminals
in the deep DCN (Zhang and Oertel 1993b). However, given
the evidence of this paper that some inhibitory inputs to vertical
cells must respond strongly to broadband noise, it seems clear that an
inhibitory input other than vertical cells is present. In addition, no
signs of inhibitory or any other interaction have been observed between
pairs of type II units in cross-correlation studies (Voigt and
Young 1980
, 1990
).
Third, D-stellate or radiate neurons of the VCN project
axons to DCN that terminate in regions where vertical cell dendrites are located (Doucet and Ryugo 1997; Oertel et al.
1990
). These neurons are glycine-immunoreactive (Doucet
et al. 1999
) and so could provide inhibitory inputs to vertical
cells (Zhang and Oertel 1993b
). These neurons have been
shown to give the so-called onset-C response (Smith and Rhode
1989
), a prominent feature of which is wideband facilitation,
which causes them to respond more strongly as the bandwidth of the
stimulus is increased (Jiang et al. 1996
; Palmer
et al. 1996
; Winter and Palmer 1995
). In
particular, onset-C neurons respond more strongly to noise than to
tones. On this basis, Winter and Palmer (1995)
proposed
that onset-C neurons form the inhibitory inputs to DCN type II units
that produce weak type II noise responses in the presence of strong
tone responses. Current models of the response properties of both type
II and type IV units in DCN are based on inhibitory input of the kind provided by onset-C neurons, the so-called wideband inhibitor (Blum and Reed 1998
; Davis et al. 1996
;
Hancock and Voigt 1999
; Hancock et al.
1997
; Nelken and Young 1994
, 1997
).
Figure 12 shows two comparisons of
properties of type II units and onset-C units. The onset-C properties
are taken from guinea pig data of Palmer and colleagues (Jiang
et al. 1996; Palmer et al. 1996
). In those
papers, onset-C units were often not segregated from other onset unit
types, when the properties of the different unit types were the same.
Nevertheless, in the ensuing discussion we refer only to onset-C units
because that subclass is the candidate inhibitory input to type II
cells. Figure 12A shows the total bandwidth data from
Fig. 4A repeated (+) along with the bandwidths of
excitatory tuning curves for onset neurons (
) (from Jiang et
al. 1996
). These data show that the two-tone inhibitory areas
of type II units have roughly the same bandwidth as the excitatory
tuning curves of onset (and onset-C) neurons. Thus if onset-C neurons are the source of the inhibitory inputs to type II units, little or no
convergence across BF is necessary to produce the inhibitory regions of
two-tone response maps. In fact, because onset-C neurons show wideband
facilitation, the use of two tones in constructing type II response map
should make the 40-dB bandwidths of presumed onset-C inputs wider than
the single-tone bandwidths shown in Fig. 12A
(Jiang et al. 1996
).
|
Figure 12, B and C, shows rate-level
curves for BF tones () and for noisebands (
), plotted slightly
differently than in Fig. 9. Each of the noiseband curves shows rate
versus sound level for noisebands of fixed spectrum level; sound level
is varied within a curve by varying bandwidth (see the bandwidth scale
at the bottom of the figure). Figure 12C
is exactly the same data as in Fig. 9B, with the points
connected up a different way. Type II units exhibit a very strong
inhibition in these plots, in the form of the near-monotonic decrease
in discharge rate as bandwidth (and stimulus energy) increase. The only
exceptions are for the narrowest bandwidths at low sound levels, where
rate increases with bandwidth. These two examples are typical of all
type II units studied.
Type II units and onset-C units behave very differently from
other cochlear nucleus neurons (Greenwood and Goldberg
1970; Palmer et al. 1996
) and auditory nerve
fibers (Ruggero 1973
; Shalk and Sachs
1980
) in plots like Fig. 12, B and
C. The insets between Fig. 12,
A and B, show schematic plots typical of
data from onset units and other VCN units. Other VCN neurons show an
increase in rate for narrowbandwidths at all sound levels and a
decrease in rate at wider bandwidths. The increase in rate at narrow
bandwidths, which also is observed in some type II units, is
interpreted as the summation of energy within the neuron's tuning
curve; the decrease in rate at wider bandwidths is interpreted as an
effect of suppression or inhibition. Onset neurons, by contrast, show only a monotonic increase in rate as bandwidth increases; the rate
increase continues up to bandwidths at least equal to BF. Note that the
rates in response to noisebands are higher than the rates in response
to BF tones at the same sound level, as shown in the
inset. The onset neuron behavior is, in fact, the exact
inverse of the behavior shown by type II units in Fig. 12, B and C (except for the increase in rate
at low levels, where the effect of summation of energy within the type
II tuning curve apparently outweighs the inhibitory
effect). Thus onset-C units have just the right
behavior to explain the accumulation of inhibition with bandwidth in
type II units, whereas other neuron types in the cochlear nucleus do
not. Specifically, other neuron types show a decrease in rate at wider
bandwidths, which is the opposite of the behavior required to account
for the type II behavior.
The arguments above show that onset-C units have the properties needed to account for several aspects of inhibition in type II units. Thus if onset-C units are not the inhibitory input to type II units, then the actual inhibitor should have properties identical to the onset-C unit.
Synaptic organization: unresolved issues
Despite the coherent picture developed in the preceding text,
there are some remaining uncertainties about type II synaptic organization. First, there are few inhibitory puncta on the somata of
vertical cells, in comparison with DCN principal cells, (Osen 1990; Saint Marie et al. 1991
) and little sign
of disynaptic IPSPs in vertical cells after auditory-nerve stimulation
in slice preparations (Zhang and Oertel 1993b
). Thus
current anatomic and in vitro studies do not provide a basis for the
strong inhibition seen physiologically. Second, the radiate
(D-stellate) neurons are glycinergic (Doucet et al.
1999
), but the noise-driven inhibition of type II units is
reduced significantly by bicuculline as well as by strychnine (Fig. 8).
The sensitivity of DCN cells to GABA antagonists has been reported
before (Caspary et al. 1987
; Evans and Zhou
1993
). It seems likely that there are GABAergic inhibitory
inputs on type II units, in addition to the glycinergic inputs from
radiate neurons. The source of these GABAergic inputs is not known,
although there are many GABAergic cells in the cochlear nucleus
(Kolston et al. 1992
; Osen et al. 1990
)
as well as GABAergic projections from the superior olivary complex
(Ostapoff et al. 1990
, 1997
). Third, the evidence from
two-tone response maps, inhibitory blockade, and noiseband widening
suggests that the inhibition in type II units is centered on or near
BF; models of type II responses assume the same thing. However, it is
not clear that D-stellate cells project in a tonotopic
fashion; indeed, injections of tracer into circumscribed regions of the
tonotopic map of DCN fill radiate cells across a wide range of the
tonotopic map in VCN (Doucet and Ryugo 1997
). Thus it is
not clear how the apparent tonotopic projection of the wideband
inhibitor would correspond to the apparently nontonotopic projection of
radiate neurons. Because the details of the anatomic circuitry of the
deep DCN are largely unknown, the relevance of these points cannot be
properly evaluated at present. More information about the anatomic
inputs to vertical cells, especially their dendritic inputs, is required.
Functional role of type II units
The role of type II units in spectral processing is that of a
narrowband inhibitor. Responses of DCN principal cells are strongly inhibited by this narrowband source. As a result, DCN principal cells
are inhibited by sharp spectral peaks close to their BF. These units
also are inhibited by a wideband source, probably the onset-C neuron
(Nelken and Young 1994), which produces the inhibition
seen in principal cells in response to notches in the stimulus spectrum
(Spirou and Young 1991
; Young et al.
1992
). Thus type II cells participate in the construction of
the exquisite sensitivity of DCN principal cells to sharp spectral
features, both peaks and notches.
Type II units also supply an inhibitory input to the VCN
(Wickesberg and Oertel 1990), but the role of type II
terminals in the VCN is less clear. Three different hypotheses have
been raised. The first is that this projection modulates the response
thresholds of VCN neurons (Paolini et al. 1998
). This
hypothesis is based on the finding that vertical cells provide a
tonotopically organized inhibitory input to bushy and stellate neurons
of the VCN (Wickesberg and Oertel 1990
) and on the
finding that injection of the GABA agonist muscimol into DCN produced a
significant lowering of the average threshold of VCN units
(Paolini et al. 1998
). The advantage of having VCN
thresholds elevated in this way by DCN activity is not clear; moreover,
the properties of the threshold elevation do not correspond to those of
type II units, which are not spontaneously active and have
high-thresholds themselves. Thus the role of type II units in
modulating VCN thresholds is not clear.
The second hypothesis is that the inhibitory projection from DCN to VCN
produces monaural echo suppression (Wickesberg and Oertel
1990). This hypothesis is based on the finding that vertical cells supply a delayed, frequency specific input to the VCN. Two-click data (Wickesberg 1996
) provide partial physiological
support for this idea, but only 19% of VCN cells showed the expected
increase in response to the second click after lidocaine injections in DCN. In general, the role of type II units in temporal processing is
hard to interpret because their temporal properties are complex and
nonlinear (Joris and Smith 1998
).
The third hypothesis on the role of the type II projection to VCN is
that it helps to reduce the effects of spectral notches caused by the
acoustical properties of the pinnae (Rice et al. 1992)
on the representation of complex sounds in the VCN (Nelken and
Young 1996
). Unlike DCN neurons, VCN cells are not inhibited by
narrow spectral peaks or notches. Presumably the inhibition from type
II units is too weak in VCN to produce the effects that are seen in
DCN. Instead the tonotopic array of type II neurons weakly inhibits VCN
principal cells except in the region of the notch itself. The result is
an enhancement of the spectral information in the notch relative to its
surround, essentially counteracting the effects of pinna acoustics in
producing the spectral notch. In this way, information about the notch
itself would be conveyed in the outputs of the DCN and information
about the spectral shape of the stimulus would be conveyed by the
outputs of the VCN.
Type II neurons may participate in all the functions proposed in the preceding text, but more information about their connections and responses to complex stimuli are required to fully evaluate these hypotheses. Nevertheless, the accumulated physiological and anatomic evidence indicate that type II neurons play an important role in establishing the response properties of a wide variety of cochlear nucleus neurons, and thus they play a crucial role in the transformations of the auditory representation that take place in the cochlear nucleus.
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ACKNOWLEDGMENTS |
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The technical assistance of C. Alesczczyk and P. Taylor is acknowledged. Helpful comments on the manuscript were received from B. May and R. Ramachandran.
This work was supported by Grants DC-00115 and DC-01387 from the National Institute on Deafness and Other Communication Disorders.
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FOOTNOTES |
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Address for reprint requests: G. A. Spirou, Dept. of Otolaryngology, P.O. Box 9200, Health Sciences Center, West Virginia University, School of Medicine, Morgantown, WV 26506-9200.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 26 February 1999; accepted in final form 30 April 1999.
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REFERENCES |
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