Download Discharge Patterns of Neurons in the Ventral Nucleus of the Lateral

Discharge Patterns of Neurons in the Ventral Nucleus of the Lateral
Lemniscus of the Unanesthetized Rabbit
RANJAN BATRA AND DOUGLAS C. FITZPATRICK
Department of Anatomy, University of Connecticut Health Center, Farmington, Connecticut 06030-3405
INTRODUCTION
The ventral nucleus of the lateral lemniscus (VNLL) is a
major auditory nucleus that sends a large projection to the
inferior colliculus. Despite its prominence, the responses of
neurons in the VNLL have not been extensively studied. In the
barbiturate anesthetized cat, responses to short tone bursts are
reported to be either sustained or onset (Adams 1997; Aitkin et
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al. 1970; Guinan et al. 1972a,b). Similar responses have been
seen in the bat Eptesicus fuscus, but in this species the VNLL
contains a specialized division, the columnar region. Neurons
in this region have extremely tightly locked onset latencies that
remain constant with changes in intensity and frequency (Covey
and Casseday 1991). In both species, most studies have emphasized monaural responses, consistent with the major input
that VNLL receives from the contralateral ventral cochlear
nucleus (VCN) (Glendenning et al. 1981; Schofield and Cant
1997; Stotler 1953). However, one study also reports significant numbers of binaural neurons (Guinan et al. 1972a,b). In
this report, we describe the responses of neurons in the VNLL
of the unanesthetized rabbit to monaural and binaural stimuli.
The VNLL is part of a cluster of nuclei that lie between the
superior olivary complex and the inferior colliculus. It is distinct from the dorsal nucleus of the lateral lemniscus, which
receives substantial inputs from binaural sources in the superior olivary complex (Glendenning and Masterton 1983; Glendenning et al. 1981; Henkel and Spangler 1983; Huffman and
Covey 1995; Shneiderman et al. 1988) and contains primarily
GABAergic neurons (Adams and Mugnaini 1984; Oliver and
Bishop 1998; Roberts and Ribak 1987; Saint Marie et al. 1997;
Shneiderman et al. 1993; Vater et al. 1997; Winer et al. 1995).
Some authors consider the VNLL to comprise all clusters of
neurons ventral to the dorsal nucleus of the lateral lemniscus
(Adams 1979, 1997; Whitley and Henkel 1984), but distinguish a dorsal division termed VNLLd. Other authors consider
VNLLd to be a distinct nucleus, termed the intermediate nucleus of the lateral lemniscus (Covey and Casseday 1991;
Glendenning et al. 1981; Saint Marie et al. 1997; Schofield and
Cant 1997; Vater et al. 1997; Winer et al. 1995). This region
receives a different complement of inputs from more ventral
regions (Glendenning et al. 1981; Huffman and Covey 1995),
contains a different proportion of neurons immunoreactive to
GABA and glycine (Oliver and Bishop 1998; Riquelme et al.
1998; Saint Marie et al. 1997; Vater et al. 1997; Winer et al.
1995), and is highly differentiated in echolocating bats (Covey
1993; Vater and Feng 1990; Zook and Casseday 1985). Ventral
to the VNLLd is a densely packed cluster of neurons. Medial
to the compact region are scattered neurons intercalated in the
fibers of the lateral lemniscus. This region has been referred to
as the lateral tegmentum (Glendenning et al. 1981) or the
medial division of the VNLL (Batra and Fitzpatrick 1997) but
also frequently either has been ignored or considered part of
the more compact lateral region.
In the rabbit, we have tentatively identified three cell groups
ventral to the dorsal nucleus of the lateral lemniscus. In the
absence of connectional and immunocytochemical informa-
0022-3077/99 $5.00 Copyright © 1999 The American Physiological Society
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Batra, Ranjan and Douglas C. Fitzpatrick. Discharge patterns of
neurons in the ventral nucleus of the lateral lemniscus of the unanesthetized rabbit. J. Neurophysiol. 82: 1097–1113, 1999. The ventral
nucleus of the lateral lemniscus (VNLL) is a major auditory nucleus
that sends a large projection to the inferior colliculus. Despite its
prominence, the responses of neurons in the VNLL have not been
extensively studied. Previous studies in nonecholocating species have
used anesthesia, which is known to affect discharge patterns. In
addition, there is disagreement about the proportion of neurons that
are sensitive to binaural stimulation. This report examines the responses of neurons in the VNLL of the unanesthetized rabbit to
monaural and binaural stimuli. Most neurons responded to contralateral tone bursts at their best frequency and had either sustained or
phasic discharge patterns. A few neurons were only inhibited. Most
sustained neurons were classified as short-latency sustained (SLsustained), but a few were of long latency. Some SL-sustained neurons exhibited multiple peaks in their discharge pattern, i.e., they had
a “chopper” discharge pattern, whereas other SL-sustained neurons
did not exhibit this pattern. In ordinary chopper neurons, the multiple
peaks corresponded to the evenly spaced action potentials of a regular
discharge. In unusual chopper neurons, the action potential associated
with a particular peak could fail to occur during any one presentation
of the stimulus. Unusual chopper neurons had a relatively irregular
discharge. Phasic neurons were of two types: onset and transient.
Onset neurons typically responded with a single action potential at the
onset of the tone, whereas transient neurons produced a burst of action
potentials. Transient neurons were relatively rare. About half the
neurons also were influenced by ipsilateral stimulation. Most binaurally influenced neurons were either sensitive to interaural temporal
disparities (ITDs) or excited by contralateral stimulation and inhibited
by ipsilateral stimulation. Neurons sensitive to ITDs were mostly of
the onset type and were embedded in the fiber tract medial to the main
part of the nucleus. Neurons inhibited by ipsilateral stimulation could
be of the sustained or onset type. The sustained neurons were located
on the periphery of the main nucleus as well as in the fiber tract. Most
of the monaural neurons were in the main, high-density part of VNLL.
The present results demonstrate that the VNLL contains neurons with
a heterogeneous set of responses, and that many of the neurons are
binaural.
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R. BATRA AND D. C. FITZPATRICK
METHODS
Surgery and recording
Six female Dutch-belted rabbits (;2 kg) with clean external ears
were used in these experiments. The preparatory surgery already has
been described (Batra and Fitzpatrick 1997). Each rabbit was prepared
for recording in two steps. During both steps, the rabbit was anesthetized with a mixture of ketamine and xylazine (35 and 5 mg/kg im).
In the first step, the dorsal surface of the skull was exposed surgically
using aseptic techniques, and a short metal rod was mounted on it.
After the surgery, while the animal was still anesthetized, custom ear
molds were made by inserting a short metal rod into the external
meatus and pressing ear impression compound (Audalin, Esschem,
Essington, PA) in around it. Later, the rod was replaced with a plastic
or stainless steel tube. After the first step, 1–2 wk were spent acclimating the rabbit to body and head restraint, and to the ear molds. The
second step was to drill a small hole (2– 4 mm) in the skull above the
VNLL to permit passage of the electrode. A topical antibiotic then
was applied to the exposed dura, and the hole capped with elastopolymer (Smith and Nephew Rolyan, Germantown, WI). The rabbit was
allowed several days to recover before recording sessions were initiated.
During a recording session, the rabbit was restrained in a plexiglass
couch with a body stocking and nylon straps. The head was held
stationary by clamping the metal rod implanted on the skull. The ear
molds were inserted, the elastopolymer cap removed, and the exposed
dura desensitized with lidocaine. The dura then was pierced with a
hypodermic needle inside which rode either a metal electrode (glasscoated Pt-W, 20 – 40 MV) or a micropipette. When a micropipette was
used, the hypodermic needle was sometimes omitted. The electrode
was advanced using a Burleigh microdrive, which, along with data
collection and acoustic stimulation, was controlled from outside the
booth. During the session, the rabbit was monitored using a video
camera. Each session lasted 2–3 h, or less if the rabbit moved. About
20 – 40 recording sessions were performed with each rabbit.
The activity of single neurons was discriminated using a timeamplitude window discriminator (BAK Electronics, Germantown,
MD). Single neurons were distinguished from multiunits based on the
uniformity of the amplitude and the waveform.
Acoustic stimulation and calibration
Pure tone bursts (4 ms rise and fall times, typically 75 ms long,
repeated every 200 ms) were produced digitally using dual synthesizers designed at the University of Wisconsin, one for each ear (Rhode
1976). These synthesizers were controlled by a PDP-11 computer,
which also controlled data collection. The tone bursts were delivered
through DT-48 earphones (8 V, Beyerdynamic, Hicksville, NY) connected to the tubes that ran through the ear molds.
Acoustic calibration was performed in one of two ways. In the first
two animals, the intensity of the stimuli was set relative to a standard
calibration. After the last recording session with each rabbit, the
animal was deeply anesthetized, and the true calibration in dB SPL (re
20 mPa) was measured using a calibrated microphone and probe. The
probe was inserted through a hole drilled in the wall of the bony
external meatus, opposite the tympanum. The gap around the hole was
sealed before calibrations were performed. With this method of calibration, it was not possible to maintain a constant intensity while
testing a neuron at different frequencies, because the true intensities
were only determined after experiments on each rabbit were concluded. For this reason, tuning characteristics were not determined for
neurons studied in these animals.
In the remaining animals, the tube through the ear molds was made
of stainless steel rather than plastic and incorporated a fine probe for
calibration which extended ;1 mm beyond the sound delivery tube.
When inserted, the tip of the probe was ;2 cm from the tympanum.
In these animals, calibrations were performed through the probe
before recordings were initiated, and intensities were set relative to
this calibration.
Localization of recording sites
For each electrode penetration, the position of the electrode was set
relative to a reference mark on the skull. The depth at which each
neuron was studied was recorded. In three animals, locations of
recording sites were reconstructed chiefly from reference marks that
were made at selected sites during the last recording session. In one of
these animal, the marks were made electrolytically (10 mA for 10 –20
s). In the other two animals, the marks were made by injecting
biotinylated dextran or fluorescein conjugated latex microspheres
through a micropipette which also could be used to record neural
activity.
In the remaining animals, most recordings were made with micropipettes (tip diam ;1–15 mm) that were loaded with phosphate-buffered
saline containing 10% dextran tagged with one of a variety of fluorescent labels or with biotin (Molecular Probes, Eugene OR; D1817,
D1820, D1956, D1976, D3312, D7153). Many recording sites in these
animals were marked directly by iontophoretic injection of the label
(2.5 mA 3 1.25–5 min).
On conclusion of recordings from an animal, it was anesthetized
deeply and perfused with a washout followed by a fixative containing
4% paraformaldehyde and 0.2% glutaraldehyde, according to the
procedures of Hill and Oliver (1993) for rats. The brains were blocked
in the plane of the electrode tracks, placed in 30% sucrose for several
days and frozen-sectioned (50 mm). In brains with injections of
markers, alternate sections were mounted for visualization of the
fluorescent markers (in, e.g., Fluoromount G, Southern Biotechnology
Associates, Birmingham, AL). The remaining sections were processed
using an avidin-biotin-horseradish peroxidase (HRP) complex (ABC
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tion, we have not distinguished distinct nuclei in this region.
The VNLLl and VNLLm correspond to the compact ventral
region and the neurons intercalated in the medial limb of the
lateral lemniscus, respectively. The VNLLd comprises neurons
between VNLLl and the dorsal nucleus of the lateral lemniscus, which are distributed with a density intermediate between
VNLLl and VNLLm.
Because the principal input to the VNLL is from the contralateral VCN, a major question is to what degree the sustained and onset responses in the VNLL reflect these inputs.
The sustained responses are reported to be similar to those
observed in the VCN (Covey and Casseday 1991; Guinan et al.
1972a,b). In both the VNLL and the VCN, they include a
primary-like discharge pattern that resembles the pattern produced by auditory nerve fibers and a chopper discharge pattern
consisting of multiple peaks (responses in the VCN reviewed
by Rhode and Greenberg 1992). In the VCN, neurons with a
primary-like discharge pattern are characterized by a more
irregular discharge than those with a chopper pattern (Blackburn and Sachs 1989; Young et al. 1988). Despite apparent
agreement on the types of discharge patterns encountered in the
VNLL, there is disagreement as to the proportions of neurons
displaying different patterns. It is possible that this disagreement is a consequence of the use of anesthesia, which is known
to influence discharge patterns (Brownell et al. 1979; Kuwada
et al. 1989; Ritz and Brownell 1982).
The present study examines the discharge patterns of neurons in the VNLL of the unanesthetized rabbit and compares
these patterns with those observed in other studies of the
VNLL and in the VCN.
RESPONSES IN THE VNLL
Kit, Vectastain) to visualize injected biotinylated dextran (see Hill and
Oliver 1993) and counterstained with neutral red or thionin. In the
brain with only electrolytic lesions, alternate sections were stained
with thionin to visualize the lesions. Locations of the marked sites
were reconstructed relative to the Nissl cytoarchitecture visible in the
counterstained sections using a conventional camera lucida or a computer-aided tracing system (Neurolucida, Microbrightfield, Colchester, VT). Three representative sections through the VNLL that covered its anteroposterior extent then were drawn, using the histological
sections as a guide. Locations of marked sites then were transferred to
one of the three representative sections by aligning the cytoarchitecture in the two drawings.
Analysis
CLASSIFICATION AND ANALYSIS OF POSTSTIMULUS TIME HISTOGRAMS. The discharge patterns of neurons were classified based on
ANALYSIS OF VARIABILITY. The analysis of variability to determine
whether the discharge of a neuron was regular or irregular was
performed in a manner similar to that previously described by others
(Blackburn and Sachs 1989; Bourk 1976; Young et al. 1988). Our
parameters were identical to those of Young et al. (1988) with two
exceptions. First, the binwidth was 0.5 or 1 ms (compared with 0.1 or
0.2 ms), and no smoothing was used. Second, the average coefficient
of variation (CV) was calculated over the interval 35– 65 ms (as
compared with 12–20 ms) or somewhat less if spontaneous activity
after the offset of the tone influenced the analysis (Young et al. 1988).
Tuning curves were calculated as isoresponse
contours for neurons for which responses were measured over a
sufficient range of intensities and frequencies. First, from the responses at each intensity, a contour was constructed by interpolating
the response linearly at 100 equally spaced frequencies. Second,
visual examination of response areas and PSTHs was used to determine the minimum discharge rate at which responses could be consistently observed above variations in spontaneous activity. Finally,
the intensity at which the response passed the selected discharge rate
at each of the 100 frequencies was determined by linear interpolation.
TUNING CURVES.
The measurement of latency near threshold
was complicated by the presence of spontaneous activity in many
neurons. To ensure that identifiable responses were indeed present,
threshold was defined statistically using the technique of Batra et al.
(1997a) (P , 0.001) to detect an excitatory response. The latency
measure used was the median latency of the first action potential, and
variability was assessed using the semi-interquartile range (SIQR).
The SIQR is half the interval between the 25th and 75th percentiles.
The median and the SIQR avoid some of the problems associated with
the mean latency and the standard deviation (Heil and Irvine 1997;
Young et al. 1988). The median and SIQR are less readily influenced
by the occurrence of spontaneous action potentials before the start of
the response. Such spontaneous activity necessitates special measures
in calculation of the mean and standard deviation. The median and
SIQR are also less influenced by the presence of a few responses in
which the first action potential occurs with an unusually long latency.
For a Gaussian distribution, half the area is contained in the region
between 6 SIQR, so that the SIQR 5 0.67 3 SD.
ANALYSIS OF LATENCY.
ANALYSIS OF ADAPTATION. To assess the amount of adaptation in
individual neurons, a measure similar to that of Blackburn and Sachs
(1989) was used. The mean discharge rate during 14 –18 ms after the
median latency was compared with that during 0 – 4 ms after the
median latency.
RESULTS
The results in this report are based on the responses of 174
neurons and 1 multiunit cluster in and around the VNLL that
were tested with contralateral tone bursts and other stimuli.
The multiunit cluster was included because it had a discharge
pattern not reported in lower centers and because its location
was marked. The responses of two neurons at marked recording sites in the rostral periolivary region also have been included for comparison. The responses of some of these neurons
were the subject of a previous report (n 5 17) (Batra and
Fitzpatrick 1997).
The neurons typically responded to contralateral tone bursts
(n 5 170/175). Most neurons had either sustained (n 5 74) or
phasic (n 5 86) responses to tones at their best frequency (for
details of classification scheme, see METHODS ). A few neurons
were inhibited by contralateral stimulation (n 5 10). Neurons
that were not responsive to contralateral tones were excited by
binaural low-frequency stimuli and were sensitive to interaural
temporal disparities (ITDs) at low frequencies (n 5 5). Sustained neurons were subdivided into SL-sustained, long-latency, and strongly adapting categories. Phasic neurons were
subdivided into onset and transient categories. In the following
text, the locations of different types are described, and then
sustained, phasic, and inhibited neurons are discussed in turn.
Locations of response types
The locations of most neurons were reconstructed based on
a few lesions or marking injections made after weeks or
months of recording. Based on these reconstructions, the neurons included in this study appeared to be located in the VNLL,
the adjacent reticular formation, and in the rostral superior
olivary complex immediately adjacent to the VNLL. However,
such localization is subject to considerable error. To more
accurately determine the locations of different response types,
locations of recording sites in a few animals were marked
directly with dye injections. Figure 1 illustrates the locations of
these sites collapsed onto three sections through the VNLL (see
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their responses to tone bursts at best frequency and at an intensity of
60 – 80 dB SPL. Best frequency was defined as the frequency of most
vigorous discharge, as measured at the lowest intensity at which
responses across frequency were assessed. The classes used were
similar, but not identical, to those used in the VCN because of
differences in the kinds of neurons encountered. In the first step of the
classification process, neurons were separated out that showed only
inhibition of spontaneous activity by acoustic stimulation. Classification of the remaining neurons was based on the driven responses, i.e.,
the difference between responses during the stimulus and during an
unstimulated interval (150 –200 ms after stimulus onset). Neurons that
had driven sustained responses (35–75 ms after stimulus onset) ,25/s,
with the driven transient response (0 –35 ms) greater than twice the
driven sustained response, were classified as phasic. The remaining
neurons were classified as sustained. In the VCN, a sustained discharge of 25/s, coupled with a qualitative analysis of the shape of the
poststimulus time histogram (PSTH) has been used to classify onset
neurons (Blackburn and Sachs 1989). In the present work, a more
quantitative criterion was adopted to distinguish phasic neurons from
sustained neurons. However, some neurons with driven sustained
rates between 25 and 100/s that are considered sustained here would
have been considered onset in the VCN by some authors. Phasic
neurons were divided further into onset and transient categories, based
on PSTH shape. Sustained neurons were subdivided into long-latency,
short-latency sustained (SL-sustained) and strongly adapting categories. Neurons were considered to be of long latency if their latency
was .7 ms greater than the median of neurons in our sample at
similar best frequencies (see Fig. 16A). Strongly adapting neurons
were distinguished based on the shape of their PSTHs.
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R. BATRA AND D. C. FITZPATRICK
METHODS). These sections are in the plane of the electrode
tracks that is pitched forward ;50° relative to a transverse
section through the spinal cord, so that upper portions of each
section are more anterior as well as more dorsal. The section in
Fig. 1A is the most posterior. The ventral part of this section
shows the caudal parts of VNLLl and VNLLm (l and m) where
the lateral lemniscus merges with the trapezoid body. More
dorsally, VNLLd (d) is present where the lateral lemniscus has
turned posteriorly toward the inferior colliculus. Figure 1B is a
section through the main part of VNLL. Figure 1C shows the
rostral limb of the lateral lemniscus that lies anterior to VNLLl.
The rostral limb contains a sparse population of neurons, much
like VNLLm.
The marked sites were within the boundaries of the lateral
lemniscus (Fig. 1, A–C), in a rostral portion of the ventral
nucleus of the trapezoid body (VTB, Fig. 1A), and in more
caudal olivary nuclei (not shown). None of the sites were in the
reticular formation adjacent to the lateral lemniscus. Penetrations were made medial to the marked sites in the VNLL, but
responses to acoustic stimulation were not encountered in this
region. Thus neurons sensitive to tones appear to be rare or
absent in this part of the reticular formation. Otherwise, the
distribution of the marked sites was similar to that of the
indirectly reconstructed recording sites.
The VNLLm and VNLLl contained different complements
of neurons. The VNLLm and its anterior continuation contained chiefly onset neurons (10/13) (Fig. 1, E and F), most of
which (8/10) were sensitive to ITDs at low frequencies, as
described previously (Batra and Fitzpatrick 1997). The VNLLl
contained a large proportion of SL-sustained neurons (6/10)
(Fig. 1, ‚ and Œ). Binaural neurons within VNLLl (3/10)
appeared to be on its periphery. The one marked site in VNLLd
was associated with a neuron that had an SL-sustained discharge pattern and that was inhibited by ipsilateral stimulation.
The responses of neurons in the rostral portion of the ventral
nucleus of the trapezoid body appeared similar to those of
neurons in the VNLL. Two SL-sustained neurons were located
within this region. Their latencies and response patterns were
similar to other SL-sustained neurons encountered in this
study. Thus although most of the neurons in this study were in
VNLLm and VNLLl, a few were located more dorsally in
VNLLd or more ventrally.
Sustained neurons
The most common type of sustained neuron (n 5 61/74) had
a short latency (see METHODS) and a discharge pattern that
consisted of an initial peak that declined, or adapted, to a
steady level (Fig. 2, A–D). Such SL-sustained neurons were
widely distributed in the VNLL, but the majority of marked
sites (6/10 neurons) were located in VNLLl (Fig. 1). The extent
of the adaptation in SL-sustained neurons could be large (Fig.
2, A–C) or small (Fig. 2D). The rapidity of the adaptation also
varied among neurons (compare Fig. 2, A and B with C and D).
Some SL-sustained neurons exhibited a brief “dip” in the
response after the initial transient (Fig. 2, A and B), similar to
what has previously been observed in the cochlear nucleus
(Blackburn and Sachs 1989; Pfeiffer 1966).
A few neurons had responses that declined throughout the
tone burst to near zero (Fig. 2E). These neurons were excluded
from the SL-sustained category and instead were classified as
strongly adapting (3/74 neurons). The only marked site associated with a strongly adapting neuron was in the VNLLl (Fig.
1B). Still other sustained neurons were of long latency (Fig. 2,
F–H). These neurons (10/74) had latencies .7 ms greater than
that appropriate for their best frequency (see Fig. 16A). They
exhibited two types of discharge patterns in response to tone
bursts. The more common type of long-latency neuron (7/10)
discharged with a low discharge rate (,100 action potentials/s)
(Fig. 2, F and G). One of these neurons exhibited a chopper
pattern (Fig. 2G). The less common type of long-latency neuron (3/10) produced a response that gradually built to a peak
and then declined (Fig. 2H). Examination of raster plots confirmed that this pattern was not the result of a single action
potential occurring with variable latency.
To quantify the proportion of SL-sustained neurons that
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FIG. 1. Locations of marked recording sites. Each panel depicts a section through the brainstem of the rabbit in the plane of the
electrode penetrations that is pitched forward from the transverse, so that upper portions of each panel are more anterior as well
as more dorsal. A is most posterior, C is most anterior. E, ▫, ‚, ¹, and L: neurons with monaural responses; F, ■, Œ, and }: neurons
with binaural responses. Binaural onset category includes 5 neurons sensitive to interaural temporal disparities (ITDs) previously
illustrated in Batra and Fitzpatrick (1997). Data from 3 animals have been pooled. BN, nucleus of the brachium of the inferior
colliculus; LL, lateral lemniscus; MCP, middle cerebellar peduncle; MTB and VTB, medial and ventral nuclei of the trapezoid
body; PN, pontine nuclei; Pyr, pyramids; Sag, sagulum; V, trigeminal nerve; m, l, d, medial, lateral, and dorsal divisions of the
ventral nucleus of the lateral lemniscus (VNLL).
RESPONSES IN THE VNLL
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adapted, the average discharge rate late in the response was
compared with that early in the response (see METHODS). For all
neurons the discharge rate changed by .5% (61/61 neurons),
indicating that their discharge rate was not constant during the
stimulus. Most neurons showed a decrease in the discharge rate
(53/61 neurons).
To determine whether SL-sustained neurons were similar to,
or different from, short-latency sustained neurons in the VCN
such as primary-like and chopper neurons, the initial portion of
the response of the SL-sustained neurons was examined on a
time scale similar to that commonly used in studies of that
nucleus (Figs. 3–5). Some SL-sustained neurons in the VNLL
responded to contralateral tone bursts with a chopper pattern
similar to that observed in the VCN (Fig. 3, A and B, top). In
such ordinary chopper neurons, the multiple peaks of the
chopper pattern were the result of action potentials occurring at
regular intervals during each repetition of the stimulus (Fig. 3,
A and B, 2nd row). Each peak was associated with one action
potential per repetition. In some neurons the chopping frequency was more rapid than in others (compare Fig. 3, A and
B). The chopper pattern in the PSTH was occasionally relatively sustained (Fig. 3A, top) but was typically more transient
(Fig. 3B, top).
In the VCN, neurons with a chopper pattern have a regular
discharge. The degree to which the regularity of the discharge
was maintained throughout the stimulus was assessed using an
analysis of variability (Fig. 3, 3rd and 4th rows) (see METHODS).
For ordinary chopper neurons, the standard deviation of the
interspike interval (Fig. 3, 3rd row, dotted line) was typically
less than the mean (Fig. 3, 3rd row, solid line) throughout the
stimulus. This was reflected in the CV (Fig. 3, 4th row), which
is the ratio of the standard deviation to the mean.
Other SL-sustained neurons in the VNLL showed an unusual
chopper pattern (Fig. 4). Like the ordinary chopper neurons,
these neurons also exhibited multiple peaks at the onset of the
response to tone bursts (Fig. 4, top). However, in some of these
neurons the width of the peaks did not increase gradually as in
ordinary chopper neurons, but instead later peaks were much
broader than the immediately preceding peaks (Fig. 4B, top). In
unusual chopper neurons, the initial action potential of the
response sometimes corresponded to the second or later peaks,
the first peak having been “missed” (Fig. 4, 2nd row, 3).
Some unusual chopper neurons discharged regularly, with
the standard deviation of the interspike interval considerably
less than the mean (Fig. 4A, 3rd and 4th rows). However, most
discharged irregularly, with the standard deviation more comparable to the mean (Fig. 4B, 3rd and 4th rows).
Still other SL-sustained neurons did not exhibit a chopper
pattern (Fig. 5, top). Some of these nonchopper neurons produced a well-timed initial action potential that was followed by
a brief pause (Fig. 5B). Most nonchopper neurons discharged
rather irregularly (Fig. 5, A and B, 3rd and 4th rows).
Ordinary chopper neurons were the most numerous (20/44),
and unusual chopper neurons the least (10/44). Nonchopper
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FIG. 2. Discharge patterns of 8 neurons with sustained
responses to contralateral tone bursts. A–D: short-latency
(SL) sustained neurons. E: strongly adapting neuron. F–H:
long-latency neurons. Unless otherwise stated, individual responses in this and subsequent figures were at the best frequency of the neuron. Lines under G and H indicate duration
of stimulus. Full repetition interval is plotted. Binwidth: 2 ms.
Frequencies (kHz), intensities (dB), and number of repetitions: 17.5, 81, 100 (A); 1.0, 70, 100 (B); 1.3, 66, 100 (C);
15.0, 44, 100 (D); 2.5, 70, 100 (E); 5.7, 80, 100 (F); 5.7, 70,
100 (G); and 3.4, 64, 10 (H).
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R. BATRA AND D. C. FITZPATRICK
neurons were intermediate in number (14/44). Other SL-sustained neurons (n 5 17) could not be classified in one of these
groups because they had a low discharge rate, were of low
frequency and phase-locked, or because the number of presentations was too small to make an adequate assessment.
The CVs of SL-sustained neurons were broadly distributed
around a value of 0.5 (Fig. 6, dashed line). Nearly all ordinary
chopper neurons had CVs ,0.5, indicating a regularity in their
discharge, whereas most unusual chopper neurons and nonchopper neurons discharged more irregularly, with CV * 0.5.
Phasic neurons
Phasic neurons were of two types: onset and transient. Most
phasic neurons exhibited an onset pattern (78/86; Fig. 7, A–C),
which consisted of a large peak at onset, followed by no (Fig.
7A) or few (Fig. 7B) action potentials. Sometimes, the response
after the initial peak was suppressed below the spontaneous
rate (Fig. 7C). A few phasic neurons exhibited a transient
pattern (8/86), consisting of a burst of action potentials that
could last up to ;20 ms (Fig. 7D). Most marked sites associated with onset neurons were in VNLLm or its continuation in
the rostral limb of the lateral lemniscus (10/11 neurons; Fig. 1).
The two marked sites associated with transient neurons were in
VNLLl.
Some phasic neurons also produced a discharge associated
with the offset of the stimulus. Off discharges were most
common in transient neurons (4/8) and were only occasionally
present in onset neurons (6/78). In transient neurons, this off
response occurred with a latency of .20 ms (relative to sound
offset) near best frequency, considerably more than the latency
of the response to the onset of the tone. In onset neurons, the
off discharge was usually of short latency, i.e., comparable
with that of the onset response. It is unlikely that this shortlatency off discharge was a result of spectral splatter, because
it was rarely seen and often was associated with a nonmonotonic rate-level function (see following text), which is more
consistent with the presence of an inhibitory input.
The latency of the long-latency off response could differ at
frequencies other than best frequency. Figure 8 illustrates one
neuron in which this was observed. At best frequency the
latency of the off response was long (Fig. 8A). At higher
frequencies, the latency was shorter (Fig. 8B) and comparable
with the latency of the initial phasic response (see also different
neuron in Fig. 12C). For the neuron of Fig. 8, the off response
was larger above best frequency (note change in scale), but this
was not always the case (Fig. 12C). The change in latency with
frequency was relatively abrupt, suggesting that the off responses at the different frequencies reflect rebound from different sources of inhibition.
When viewed on an expanded time scale, the discharge
pattern of onset neurons showed considerable variety, but
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FIG. 3. Regularity of 2 ordinary chopper neurons. Top:
poststimulus time histogram (PSTH) of initial part of response to a 75-ms tone burst. Second row: rasters of 30
repetitions of the stimulus. Third row: mean interval (—)
and standard deviation (dotted line) as a function of time.
Bottom: coefficient of variation as a function of time during
the stimulus. Binwidth for PSTH: 0.2 ms. Frequencies
(kHz), intensities (dB) and number of repetitions: 6.2, 56,
75 (A) and 30.0, 70, 100 (B). Best frequency of the neuron
in A was 5.0 kHz.
RESPONSES IN THE VNLL
1103
differed from the pattern displayed by transient neurons (Fig.
9). Most onset neurons responded with a single action potential
to all or most repetitions of the tone (Fig. 9, A and B). This
action potential could be locked tightly to the onset of the
sound (Fig. 9A) or it could be locked loosely (Fig. 9B). Other
onset neurons responded with two or three action potentials
(Fig. 9C). These action potentials were spaced regularly, resulting in two or three peaks in the PSTH. The interval between
the peaks typically was unrelated to the frequency of stimulation. Transient neurons responded with a burst to each presentation of the stimulus (Fig. 9D). The burst could contain as
many as seven or eight action potentials. These action potentials did not produce multiple peaks in the PSTH (Fig. 9D, top),
even though the intervals between them appeared relatively
regular (Fig. 9D, bottom).
Inhibited neurons
Some neurons were inhibited by contralateral stimulation
(n 5 10/175; Fig. 10). In half of these, the discharge rate
gradually recovered to spontaneous levels after the tone (Fig.
10A), but in the remainder, there was an off discharge after
termination of the tone (Fig. 10B). Inhibited neurons were not
excited by ipsilateral stimulation. One of the two marked sites
associated with an inhibited neuron was in VNLLm, the other
was in the limb of the lateral lemniscus that was lateral to
VNLLl (Fig. 1).
Tuning
The tuning of SL-sustained neurons (n 5 12) tended to be
narrower for neurons with higher best frequencies (Fig. 11A).
The tuning of the onset neurons tested (n 5 8) did not appear
to depend on best frequency and was quite broad (Fig. 11B,
solid line and dashed line). Transient neurons (n 5 4) tended to
have relatively sharp tuning (Fig. 11B, Tr).
Constancy of the discharge pattern
The discharge pattern of a neuron was usually maintained at
all frequencies to which it was responsive (Fig. 12). Examples
are shown of an SL-sustained neuron, an onset neuron, and a
transient neuron (Fig. 12, A–C, respectively). The response of
some SL-sustained neurons and of some transient neurons was
suppressed below the spontaneous rate at frequencies surrounding the best frequency (Fig. 12A, top, and C, bottom,
respectively). Such sideband suppression was typically more
pronounced below the best frequency in SL-sustained neurons
and above best frequency in transient neurons.
Most neurons displayed their characteristic discharge patterns across a range of intensities as well. Figure 13 shows the
responses of a SL-sustained neuron (Fig. 13A), an onset neuron
(Fig. 13B), and a transient neuron (Fig. 13C) from threshold
(Fig. 13, top) to intensities well above threshold (Fig. 13,
bottom). Each neuron maintained its discharge pattern at all
intensities.
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FIG. 4. Regularity of 2 unusual chopper neurons. Same
format as Fig. 3. 3, repetitions in which there are no action
potentials corresponding to the initial peak in the PSTH.
Repetitions averaged in each case: 100. Frequencies (kHz)
and intensities (dB): 31.0, 49 (A) and 5.6, 70 (B).
1104
R. BATRA AND D. C. FITZPATRICK
There was a small group of neurons (n 5 6) that formed a
notable exception to the rule that the discharge pattern was
similar across frequency. These neurons had high best frequencies (i.e., )2 kHz, the upper limit for phase-locking) when
assessed at a low intensity, but produced a vigorous sustained
discharge at low frequencies when stimulated with tones of
high intensity. The responses of one neuron of this group are
illustrated in Fig. 14. When tested with best-frequency tones of
low intensity (40 dB in this example), this neuron produced a
SL-sustained response consisting of a well-timed onset followed by a relatively weak sustained discharge (Fig. 14A, left).
This discharge pattern was maintained at higher intensities (70
dB, Fig. 14A, right). Other neurons in this group responded
with an onset discharge to best-frequency tones (not shown).
There was no response to low-frequency tones when the intensity was low (Fig. 14B, left), but at higher intensities the
response was vigorous (Fig. 14B, right) and was typically
stronger than that at best frequency. The low-frequency response was phase-locked (Fig. 14C). The vector strength for
phase-locking (Goldberg and Brown 1969) was typically ;0.8,
which is similar to that observed in the auditory nerve (Johnson
1980; Joris et al. 1994). Thus these neurons had a low-frequency sustained discharge that appeared to be independent of
the discharge pattern at best frequency, which could be either
SL-sustained or onset.
Dynamic range
FIG. 6. Regularity of the population of SL-sustained neurons. Most ordinary chopper neurons had coefficient of variations (CVs) less than ;0.5,
whereas most unusual chopper neurons and nonchopper neurons had CVs
)0.5. Number of neurons were: 17 (ordinary chopper); 8 (unusual chopper);
11 (nonchopper).
The dynamic range, or the range of intensities above threshold over which the response is graded, was assessed in neurons
(n 5 54) for which responses were recorded from threshold to
either saturation or 40 dB above threshold. Most of these
neurons were either SL-sustained neurons (n 5 30) or onset
neurons (n 5 16).
The response of most neurons increased monotonically from
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FIG. 5. Regularity of 2 nonchopper neurons. Same format as Fig. 3. PSTHs of nonchopper neurons did not
display the multiple peaks of chopper neurons, and their
discharge was more irregular. Repetitions averaged in each
case: 100. Frequencies (kHz) and intensities (dB): 15.0, 44
(A) and 17.0, 100 (B).
RESPONSES IN THE VNLL
1105
FIG. 7. Discharge patterns of 4 phasic neurons in response
to contralateral tone bursts. Same format as Fig. 2. Frequencies
(kHz), intensities (dB), and number of repetitions: 8.0, 70, 100
(A); 0.77, 73, 50 (B); 32.0, 70, 100 (C); and 5.7, 70, 100 (D).
Best frequency of the neuron in C was 22.6 kHz.
FIG. 8. Shift in the latency of a long-latency off discharge. A: discharge
pattern at best frequency of an onset neuron that had a long-latency off
response. Initial peak has been truncated so that the off response is more
visible. B: response of the same neuron at a higher frequency. Intensity: 70 dB.
Number of repetitions: 135 (A) and 120 (B).
Latency
Most neurons with excitatory responses had latencies of
;5–9 ms to contralateral stimulation (7.0 6 1.4 ms, median 6
SIQR, n 5 160; Fig. 16A). Some neurons had latencies .7 ms
greater than the average for a particular frequency (Fig. 16A,
- - - vs. —). All of these long-latency neurons (Fig. 16A, ■)
had sustained responses.
For many neurons, the SD of the latency of the first action
potential was not representative of the variability in latency.
An example, by no means the most extreme, is shown in Fig.
16B. During most responses, the latency was close to 7.4 ms
(Fig. 16B, histogram), except for a single repetition during
which the latency was ;50 ms. A Gaussian curve with an
equivalent SD (5.2 ms) was far broader than the main peak
(Fig. 16B, —). In contrast, a Gaussian curve with an equivalent
SIQR (0.31 ms) had a width similar to that of the main peak
(Fig. 16C, - - -). For this reason, the SIQR rather than the SD
was used as a measure of variability.
There was an overall trend for longer latencies to also be
more variable. Some onset and SL-sustained neurons had extremely short, tightly-locked latencies (Fig. 16C, E and Œ,
respectively). Others had longer latencies that were also not as
well locked to the onset of the stimulus. The latencies of
transient neurons (Fig. 16C, F) were more closely clustered
than those of SL-sustained and onset neurons, but the variability in the latency was similar to that of other neurons with
similar latency. Long-latency neurons (Fig. 16C, ■) had the
most variable onset times.
The latencies of most neurons decreased appreciably with
increasing intensity. The shift in latency was calculated over a
range of 10 –30 dB, beginning at 10 dB above threshold. Onset
and SL-sustained neurons showed a similar range of shifts in
latency with increasing intensity (Fig. 16D) as did transient and
long-latency neurons (not shown).
To establish whether any neurons in the VNLL of the
rabbit could be considered to have “constant latency” as
described in the bat Eptesicus (Covey and Casseday 1991),
we tested neurons in our sample with two criteria similar to
those used in the earlier study of Eptesicus (for a comparison of the criteria in the rabbit and Eptesicus see DISCUSSION). The first criterion was that the SIQR of the latency be
,0.67 ms (Fig. 16C, 3). Most neurons (112/160) met this
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threshold until saturation was reached (Fig. 15A, F, Œ, and };
Fig. 15B). A few neurons (n 5 7/54), displayed a nonmonotonic increase in the response (Fig. 15A, E). Most of these
neurons were phasic neurons (n 5 5/7; 4 onset, 1 transient).
Most of the nonmonotonic phasic neurons had a short-latency
off response, consistent with the notion that the nonmonotonicity was a consequence of an inhibitory input.
Onset neurons tended to have shorter dynamic ranges than
SL-sustained neurons (compare Fig. 15, A with B). The average dynamic range of onset neurons was ;20 dB (23 6 15 dB,
mean 6 SD; Fig. 15C, ■). For SL-sustained neurons, the
average dynamic range was almost 50 dB (48 6 15 dB) (Fig.
15C, h). The difference was significant (t 5 5.4, P , 0.01,
df 5 44). The dynamic range of most SL-sustained neurons
was underestimated, because responses were not typically
measured up to saturation.
1106
R. BATRA AND D. C. FITZPATRICK
criterion. The second criterion was that as the intensity was
raised the latency should shift by no more than 33 ms/dB
(Fig. 16D, 1). Fewer neurons (21/98) met this criterion.
Overall, about an eighth of the neurons tested met both
criteria (12/98) and could be considered to have a constant
latency. Some of these constant-latency neurons had onset
discharge patterns (8/12) and others had sustained discharge
patterns (4/12). If an SD ,1 ms was used as the first
criterion, then fewer neurons met both criteria (4/98).
Binaural influences
Although most neurons in the VNLL responded to contralateral stimulation, many were influenced by ipsilateral stimula-
tion as well. Some neurons were sensitive to ITDs at low
frequencies and were located chiefly in the medial part of the
nucleus. The properties of these already have been described
(Batra and Fitzpatrick 1997) and will not be discussed in detail
here. The four neurons of Fig. 17 illustrate other influences of
ipsilateral stimulation. In Fig. 17, A–C, ipsilateral tone bursts
(bar) were presented during the response of SL-sustained neurons to contralateral tone bursts. The neuron of Fig. 17A was
facilitated by ipsilateral stimulation, whereas those of Fig. 17,
B and C, were suppressed. In some neurons (Fig. 17B), the
suppression was relatively weak, whereas in other neurons
(Fig. 17C), it was stronger. Onset neurons also could display
binaural influences. The response of the neuron of Fig. 17D to
contralateral tones (1st panel) was progressively reduced as the
FIG. 10. Discharge patterns of 2 inhibited neurons. Same
format as Fig. 2. Frequencies (kHz), intensities (dB), and
number of repetitions: 22.0, 64, 100 (A) and 8.0, 80, 150 (B).
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FIG. 9. Discharge patterns of 4 phasic neurons
viewed on an expanded time scale. Top: PSTH (binwidth: 0.2 ms); bottom: raster of 30 stimulus presentations. Repetitions averaged in each case: 100.
Frequencies (kHz) and intensities (dB): 22.0, 70 (A);
3.0, 80 (B); 8.0, 70 (C); and 1.0, 64 (D).
RESPONSES IN THE VNLL
1107
inhibited. Both the sustained and phasic groups contained some
subgroups not previously described. These include long-latency and strongly adapting neurons in the sustained group and
transient neurons in the phasic group.
Many neurons in the VNLL were influenced by ipsilateral
stimulation as well as being driven by contralateral stimulation.
The two major types of binaural interaction were suppression
of contralateral responses by concomitant ipsilateral stimulation and sensitivity to ITDs. Both sustained and onset neurons
could exhibit binaural suppression, but sensitivity to ITDs
occurred chiefly in onset neurons. The evidence indicates that
onset neurons sensitive to ITDs, inhibited neurons, and some
sustained neurons exhibiting binaural suppression are located
in VNLLm, whereas VNLLl contains transient neurons, monaural sustained neurons, and, at its margins, some neurons
exhibiting binaural suppression.
FIG. 11. Tuning curves of neurons in the VNLL. Tuning curves for 26
neurons were constructed as described in METHODS. A: tuning curves of four
SL-sustained neurons. B: tuning curves of 4 phasic neurons. Tr, transient
neuron. Other tuning curves in B are those of onset neurons.
intensity of simultaneously presented ipsilateral tones was increased (I 5 55–75 dB).
The distribution of neurons in the sample across binaural
categories is illustrated in Fig. 18A. Slightly less than half of
the neurons (40%) responded to only contralateral stimulation.
Of these, most were excited by contralateral tones (E0), but a
few were inhibited (I0). The major categories of binaural
influences present were ipsilateral suppression combined with
contralateral excitation (EI) and sensitivity to ITDs at low
frequencies. Most EI neurons had a SL-sustained discharge
pattern (23/41), but several had an onset discharge pattern
(14/41). Most ITD-sensitive neurons had an onset discharge
pattern (36/44). Two high-frequency onset neurons that were
sensitive to ITDs at low frequencies were classified as being
ITD sensitive. About 10% of neurons tested were sensitive to
ITDs in the envelopes of sinusoidally modulated best-frequency tones, and most of these were EI.
Among the EI neurons, the strength of suppression was
widely distributed. To quantify the strength of ipsilateral inhibition, the percent suppression of the response at the highest
ipsilateral intensity tested was calculated, relative to the response to contralateral stimulation alone (Fig. 18B). Neurons
were more or less uniformly distributed by this measure. This
indicates that among EI neurons the ipsilateral inhibition could
vary from being very weak to near total.
DISCUSSION
Neurons in the VNLL of the unanesthetized rabbit responded to pure tone bursts at the contralateral ear with a
variety of discharge patterns. In agreement with earlier studies
(Adams and Mugnaini 1990; Aitkin et al. 1970; Covey and
Casseday 1991; Guinan et al. 1972a,b), most exhibited sustained or phasic patterns, and a lesser number were only
It is unlikely that the discharge patterns observed in the
present study represent those of axons ascending in the lateral
lemniscus rather than those of neurons in the VNLL itself. The
axons of the neurons in the medial and lateral superior olives
that are the primary encoders of ITDs are known to ascend in
the lateral lemniscus. Although neurons sensitive to ITDs were
found in the VNLL, none of these neurons displayed the
signature phase-locking and sensitivity to ITDs of primary
encoders of ITD (Batra et al. 1997b). The absence of any
recordings from the axons of neurons in the medial and lateral
superior olives suggests that the responses reported here were
from cell bodies and not axons.
The proportions of neurons with different discharge patterns
found in the present study differ from those in previous studies of
the VNLL. Several small populations have not been reported
previously. These include transient neurons, inhibited neurons,
long-latency neurons, and strongly adapting neurons. The proportion of sustained neurons that display a chopper pattern is lower
than in earlier studies (Adams 1997; Guinan et al. 1972a,b). This
most likely reflects the use of anesthesia in the earlier work which
is known to influence the discharge pattern (Brownell et al. 1979;
Kuwada et al. 1989; Ritz and Brownell 1982). There is evidence
in the lateral superior olive that anesthesia decreases the proportion of neurons with chopper discharge patterns (Batra et al.
1997b; Brownell et al. 1979). The proportion of onset neurons is
also higher in the present study than previously reported. However, this is probably due to an oversampling of VNLLm, which
contains chiefly onset neurons.
Sources of discharge patterns
The different subtypes of SL-sustained discharge patterns
that are present in the VNLL also are observed in the VCN
(reviewed by Rhode and Greenberg 1992). At first glance, the
chopper neurons in the VNLL appeared broadly similar to
those in the VCN. A few neurons in the VNLL exhibited what
appeared to be sustained chopper patterns, whereas others
exhibited transient chopper patterns. Similarly, the nonchopper
neurons of the VNLL produced discharge patterns that were
similar to the primary-like and primary-like-with-notch patterns reported in the VCN.
Despite these similarities, there were differences. The dy-
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Discharge patterns in the VNLL
1108
R. BATRA AND D. C. FITZPATRICK
namic range of SL-sustained neurons was considerably larger
than that of most neurons in the VCN. Most neurons in the
VCN have dynamic ranges of ;25 dB (Rhode and Smith
1986). An exception are the Oc neurons (which, despite their
name, do have substantial sustained discharge rates). These
neurons have an average dynamic range of 57 dB, similar to
the SL-sustained neurons of the VNLL. However, it is unlikely
that the wide dynamic range of the SL-sustained neurons is
inherited from the Oc neurons or from sustained neurons in
medial periolivary regions that also have a wide dynamic range
and are sensitive to contralaterally presented sounds (Kuwada
and Batra 1999). The axonal terminations of Oc neurons within
the VCN contain pleomorphic vesicles (Smith and Rhode
1989), suggesting they are inhibitory. There is also evidence
that, for the most part, the Oc neurons project only to the
contralateral cochlear nucleus (P. H. Smith, personal communication). The projection from medial periolivary regions to the
VNLL is sparse (Glendenning et al. 1981). Thus it is more
likely that the wide dynamic range of neurons in the VNLL is
a result of neural processing in the VNLL itself and is a
consequence of the convergence of inputs from the VCN that
encode different ranges of intensity. Some sustained neurons in
the VNLL of Eptesieus also have wide dynamic ranges (Covey
and Casseday 1991).
Another way in which SL-sustained neurons differed from
sustained neurons in the VCN was in the significant proportion
of unusual chopper neurons. These neurons likely correspond
to “unusual neurons” in the VCN that exhibit a multipeaked
discharge pattern but do not fire an action potential for each
peak during each presentation of the stimulus (Blackburn and
Sachs 1989). In the VCN, they are reported to be rare (,3% of
neurons). It is unlikely that the responses of unusual chopper
neurons arise by the cellular mechanisms usually considered to
give rise to chopper discharge patterns in the VCN. Models of
chopper discharge patterns in the VCN typically do not assume
an internal oscillator (e.g., Arle and Kim 1991). Instead, they
assume a steady synaptic input that is integrated to generate an
action potential. The timing of action potentials then is determined by the level of synaptic input and the time of the
preceding action potential. Without an internal oscillator, or a
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FIG. 12. Discharge patterns of 3 neurons as a function of
frequency. A: SL-sustained neuron. B: onset neuron. C:
transient neuron. Binwidth: 5 ms. Intensities (dB), number
of repetitions: 49, 10 (A); 70, 25 (B); and 60, 10 (C).
RESPONSES IN THE VNLL
1109
FIG. 13. Discharge patterns of 3 neurons as a function of
intensity. A: SL-sustained neuron. B: onset neuron. C: transient neuron. Binwidth: 2 ms. Frequencies (kHz), number of
repetitions: 42.0, 25 (A); 5.5, 25 (B); and 19.0, 20 (C).
at higher frequencies suggests that there may be two different
off responses generated by inhibitory rebound from two different sources of inhibition. The short-latency off response
present at higher frequencies may be a consequence of rebound
from an inhibitory input active during the stimulus. The longlatency off response present near best frequency may be the
result of rebound from a delayed inhibitory input or one that
lasts longer. Alternatively it may be rebound from an inhibitory
input that is activated transiently at the offset of a stimulus.
Neurons with a strong, short-latency off response are present in
the superior olivary complex (Kuwada and Batra 1999), most
likely in a region surrounding the medial superior olive. It is
possible that these neurons provide inhibition to the VNLL,
although, as remarked earlier, input from this region to the
VNLL appears sparse (Glendenning et al. 1981).
The inhibited discharge pattern also does not appear to be
inherited via the input from the VCN. Such responses could be
the result of inhibitory projections from the superior olivary
complex. One possible source of inhibition in this region is the
medial nucleus of the trapezoid body. The principal neurons of
this nucleus receive contralateral input (e.g., Cant and Casseday 1986; Stotler 1953; Tolbert et al. 1982; Warr 1972, 1982)
and are immunoreactive to glycine, a known inhibitory transmitter (Adams and Mugnaini 1990; Wenthold et al. 1987).
They are known to project to the VNLL (Casseday et al. 1988;
Glendenning et al. 1981; Sommer et al. 1993; Spangler et al.
1985). Glycinergic endings occur in the VNLL (Oliver and
Bishop 1998; Saint Marie et al. 1997), and there are neurons in
this nucleus that have receptors for glycine (Glendenning and
Baker 1988). Alternatively, inhibitory responses could arise
from local collaterals of neurons within the VNLL itself (Zhao
and Wu 1998), which contains many glycinergic neurons (Oliver and Bishop 1998; Riquelme et al. 1998; Saint Marie et al.
1997; Vater et al. 1997; Winer et al. 1995).
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periodic input, it is difficult to see how the periodicity could be
maintained without the generation of an action potential. It is,
however, possible that unusual chopper neurons in the VNLL
get input from the ordinary chopper neurons of the VCN.
As with the SL-sustained neurons, onset neurons are present
in both the VCN and the VNLL. There is evidence that some
of the onset responses in the VNLL are inherited via inputs
from the VCN octopus cells, which appear to project to the
VNLL and terminate there in calyceal endings (Adams 1997;
Joris et al. 1992; Schofield and Cant 1997). Such endings
would serve to faithfully reproduce the onset discharge pattern
of octopus cells in neurons of the VNLL. Some of the neurons
encountered in the present study did have properties similar to
those posited for octopus cells (Godfrey et al. 1975; Joris et al.
1992). They had a well-timed onset and a discharge pattern that
was onset or sustained with a relatively low sustained discharge rate. They also synchronized strongly to low-frequency
tones. These neurons could well have received their input from
octopus cells of the VCN.
Many other onset neurons encountered in the present study did
not appear to have inherited their discharge pattern from octopus
cells. These onset neurons were of low best frequency, were
sensitive to ITDs, and were located chiefly in VNLLm. At low
frequencies, octopus cells do not produce an onset response but
instead a sustained, phase-locked discharge. Furthermore the calyceal endings that are believed to come from octopus cells have
been reported only in VNLLl. Thus there appear to be multiple
populations of onset neurons within VNLL.
In contrast with the SL-sustained and onset neurons, transient neurons appear to be novel to the VNLL. Such responses
may be the consequence of unusual membrane properties of
these neurons or may reflect an inhibitory input following an
excitatory input by 10 –20 ms. The presence of an off response
in some of these neurons is consonant with the presence of an
inhibitory input. The decrease of the latency of the off response
1110
R. BATRA AND D. C. FITZPATRICK
FIG. 14. Responses of a neuron that synchronized to low-frequency tones
of high intensity. A: discharge patterns at best frequency (3.25 kHz). B:
discharge patterns at a low frequency (707 Hz). Binwidth: 2 ms. C: phase
histogram depicting synchrony to 707 Hz at 70 dB.
Constancy of latency
In the VNLL of the rabbit, there did not appear to be distinct
populations of constant latency and variable latency neurons.
Instead there appeared to be a continuum such that neurons
with less variable latencies responded sooner than those with
more variable latencies. This relationship appears to be at least
partially inherited from the auditory nerve (Heil and Irvine
1997). Thus the VNLL of the rabbit differs from that of
Eptesicus. In Eptesicus, distinct populations of constant and
variable latency neurons occur, and constant latency neurons
have shorter latencies than variable latency neurons (Covey
and Casseday 1991). Despite this difference between the two
species, some of the neurons in the rabbit appeared to qualify
as constant latency responders as defined in Eptesicus.
Our criteria for constant latency responders differed from
those employed in the study of Eptesicus (Covey and Casseday
1991). In that study, constant latency neurons were defined as
“having a SD in first-spike latency of ,1.0 ms and a change of
,1.0 ms in first-spike latency as SPL was increased from 10
dB above threshold to 40 dB above threshold.” A problem with
such a definition is that the SD of the latency is sometimes a
poor descriptor of the variability because of the occurrence of
a few long-latency responses (cf. Fig. 16B) or the presence of
spontaneous activity, or both (Heil and Irvine 1997; Young et
al. 1988). This problem was absent in the study of Eptesicus
FIG. 15. Dynamic range. A: rate-level functions for 4 onset neurons. B:
rate-level functions for 4 sustained neurons. C: comparison of dynamic ranges
for onset and sustained neurons.
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because in the VNLL of that animal constant-latency responders have no spontaneous activity (Covey and Casseday 1991)
and no long-latency responses (E. Covey, personal communication). In the present study, a somewhat different criterion
was substituted, based on the SIQR of the latency (SIQR ,
0.67). Our criterion corresponds to the first criterion of the
study in Eptesicus when the distribution of latencies of individual neurons is Gaussian.
Our second criterion also differed from that in the earlier
study. The shift in latency with intensity was not measured 40
dB above threshold in neurons with higher thresholds because
such high intensities could startle the unanesthetized rabbit. If
a linear decrease in latency with level is assumed over the 30
dB range, then 1.0 ms of shift in the study on Eptesicus
corresponds to a shift of 33 ms/dB (Fig. 16D, 1). This assumption probably underestimates the number of neurons that
meet this criterion for having a constant latency because shifts
in latency are typically not linear with level and are larger at
lower intensities. A smaller proportion of neurons met this
criterion than the first criterion (see Fig. 16C).
Regardless of the particular criteria used, there appeared to
be a small proportion of constant-latency neurons in the rabbit.
RESPONSES IN THE VNLL
1111
This suggests that the large population of such neurons in
Eptesicus arose by differential amplification of neurons that are
common to other species as well. In the rabbit, such neurons
appear to represent part of a continuum, whereas in Eptesicus
the continuum appears to have been differentiated into constant- and variable-latency types.
Localization of response types
Most of the neurons studied here were localized directly or
indirectly to VNLLl or VNLLm and a few were localized to
VNLLd. Recordings from neurons in the superior olivary complex and from neurons in more rostral structures were excluded
as far as possible. The region we and others have called
VNLLd (Adams 1979, 1997; Whitley and Henkel 1984) also
has been referred to as the intermediate nucleus of the lateral
lemniscus (Glendenning et al. 1981; Saint Marie et al. 1997;
Schofield and Cant 1997). We have selected the present nomenclature partly because the majority of the neurons in our
sample were from the more ventral portions of VNLL and it
was convenient to refer to the entire region with a single name
and partly because the boundary between the two regions was
not sharply delineated in our material.
Different response types were partly segregated within the
VNLL. Sustained neurons predominated in the VNLLl, whereas
onset neurons predominated in the VNLLm. Also, the majority
of neurons in VNLLl were monaural, whereas the majority in
VNLLm were binaural and often sensitive to ITDs. Although
we consider VNLLm and VNLLl to be divisions of the VNLL,
they may be more properly considered separate nuclei because
of the differences in cytoarchitecture and neural responses.
FIG. 17. Responses of 4 binaural neurons. A: SL-sustained neuron facilitated by ipsilateral stimulation. B:
SL-sustained neuron weakly suppressed by ipsilateral
stimulation. C: SL-sustained neuron strongly suppressed
by ipsilateral stimulation. D: onset neuron suppressed by
ipsilateral stimulation. In A, B, and C a 300-ms contralateral tone is presented at 0 ms. Lines under each panel
denote ipsilateral stimulation. In D, each PSTH depicts
the response 4 – 8 ms after onset of a 75-ms tone burst.
Left panel in D: contralateral stimulation alone at 60 dB.
Other panels: binaural stimulation with progressively
higher ipsilateral intensity levels, given in dB. Frequencies (kHz): 1.3 (A); 8.5 (B); 5.0 (C); and 4.0 (D). Ipsilateral/contralateral intensities (dB): 49/64 (A); 67/77 (B);
and 64/74 (C).
Downloaded from http://jn.physiology.org/ by 10.220.33.6 on June 16, 2017
FIG. 16. Analysis of latency for neurons in the
vicinity of the VNLL. A: median latency as a function
of best frequency. —: smooth curve, constructed by
first calculating median latencies across neurons in
half-octave bands of best frequency from 0.71 to 32
kHz, and then fitting these values by eye. - - -: same
curve shifted upward 7 ms. Neurons with latencies
above - - - were considered to be of long latency. B:
difference between SD and semi-interquartile range
(SIQR) as a measure of variability of the latency.
Histogram: latency distribution for a sample neuron
(repetitions: n 5 100; responses: n 5 69). —: Gaussian curve with SD equal to that of latency distribution.
- - -: Gaussian curve with SIQR equal to that of latency distribution. C: variability of the latency. Line is
a power function least-squares fit to the data. Multiplier: 0.957; exponent: 1.90; r: 0.72. Each symbol in
A and C is a different neuron. D: shift in latency with
intensity for SL-sustained and onset neurons. 3 and
1 in C and D, respectively, are criterion levels for
constancy of the latency. Latency measurements have
not been corrected for the acoustic delay of 0.2 ms.
1112
R. BATRA AND D. C. FITZPATRICK
whether the region we call VNLLm was included in their definition of VNLL. Guinan et al. (1972b) do, in fact, illustrate several
binaural onset neurons near the medial border of VNLL. These
neurons may have been in VNLLm. Conceivably the two studies
sampled different populations, resulting in different estimates of
the number of binaural neurons.
In sum, the VNLL contains different groups of neurons with
a variety of monaural and binaural response properties. The
responses of many neurons reflect the prominent input from the
VCN, but some response properties are emergent in the VNLL.
FIG. 18. Binaurality of neurons in the vicinity of the VNLL. A: number of
neurons in each binaural category. For explanation of categories, see text. n 5
159. B: Histogram depicting degree of suppression in neurons that showed
binaural suppression. Percent suppression is the response at the highest ipsilateral intensity tested (typically 10 –20 dB above the level at the contralateral
ear), relative to the response to contralateral stimulation alone. Contralateral
intensity level was typically 50 –70 dB SPL. n 5 37.
Received 6 November 1998; accepted in final form 26 May 1999.
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The VNLL of other species also contains regions similar to
what we have termed VNLLm in the rabbit. The VNLLm probably corresponds to the “lateral tegmentum” of the cat (Glendenning et al. 1981). However, for reasons we have already given
(Batra and Fitzpatrick 1997), we prefer the term VNLLm. The
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The partial segregation of monaural and binaural neurons provides a possible reconciliation between two earlier reports that
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VNLL (Aitkin et al. 1970; Guinan et al. 1972a,b). Aitkin et al.
(1970) found that few neurons in the VNLL were binaural (11%),
whereas Guinan et al. (1972a,b) found a substantial number of
binaural neurons (35%). Neither of these studies specifically state
We thank S. Kuwada and B. D’Angelo for useful comments on the manuscript, and P. J. May for bringing the original definition of the paralemniscal
zone to our attention. L. Seman and D. C. Bishop provided histological and
technical assistance.
This research was supported by National Institute on Deafness and Other
Communication Disorders Grants PO1 DC-01366, DC-02178, and DC-00189.
During final revisions of the manuscript, R. Batra was supported by Grant IBN
9807872 from the National Science Foundation.
Address reprint requests to: R. Batra.
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