Intracellularly Labeled Fusiform Cells in Dorsal Cochlear Nucleus of the Gerbil. II. Comparison of Physiology and Anatomy
Abstract
Intracellularly Labeled Fusiform Cells in Dorsal Cochlear Nucleus of the Gerbil. II. Comparison of Physiology and Anatomy
Kenneth E. Hancock1 and Herbert F. Voigt1,21Department of Biomedical Engineering and Hearing Research Center and 2Department of Otolaryngology, Boston University, Boston, Massachusetts 02215-2407
The Journal of Neurophysiology Vol. 87 No. 5 May 2002, pp. 2520-2530.
Abstract
Hancock, Kenneth E. and
Herbert F. Voigt.
Intracellularly Labeled Fusiform Cells in Dorsal Cochlear Nucleus
of the Gerbil. II. Comparison of Physiology and Anatomy.
J. Neurophysiol. 87: 2520-2530, 2002.
Fusiform
cells represent the major class of dorsal cochlear nucleus (DCN)
projection neuron. Although much is understood abouttheir physiology
and anatomy, there remain unexplored issues withimportant functional
implications. These include interspeciesdifferences in DCN physiology
and the nature of the cell-to-cellvariations in fusiform cell
physiology. To address these issues,a quantitative examination was
made of the physiology and anatomyof 17 fusiform cells from a
companion study. The results suggestthat the basal dendrites
of gerbil fusiform cells may be electrotonicallymore compact than
those of the cat. This relative decrease inthe filtering of excitatory
inputs might account for the lowerincidence of type IV units in that
species. These data also suggestthat the gerbil DCN lacks the
high-frequency specialization describedin the cat, because the
tonotopic arrangement of the gerbil fusiformcells quantitatively
matches the place-frequency map for the gerbilcochlea. Certain
physiological properties have anatomical correlates.First, the basal
dendrites of low spontaneous rate cells are directedaway from the soma
only in the caudal direction, while the highspontaneous rate cells
have basal dendrites extending rostrallyand caudally. Second, input
resistance was dominated by the surfacearea of the apical dendrite.
Third, the discharge pattern wascorrelated with apical dendrite
orientation. Finally, there wasa spatial gradient of sensitivity to
broadband noise organizedat least partially within an isofrequency
axis. Such trends indicatethat neighboring fusiform cells are endowed
with different signalprocessingcapabilities.
Introduction
The cochlear nuclei are the sole
target of the auditory nerve (AN) and as such represents an obligatory
processing stage inthe ascending auditory pathway. The laminated
dorsal cochlearnucleus (DCN) contains a variety of morphological cell
types exhibitingdiverse physiological responses. The outputs of the
DCN arisefrom fusiform cells and giant cells, which project via the
dorsalacoustic stria to the contralateral inferior colliculus
(Adamsand Warr 1976
). Fusiform cells are readily
identified by largecell bodies and bipolar dendritic fields
(Brawer et al. 1974;Lorente de Nó
1981). In the superficial layer, spinous apicaldendrites
interact through a network of granule cells and cartwheelcells
(Berrebi and Mugnaini 1991; Golding and Oertel
1997; Mugnainiet al. 1980) with somatosensory
(Itoh et al. 1987; Weinberg andRustioni
1987; Wright and Ryugo 1996), vestibular
(Burian andGstoettner 1988; Kevetter and
Perachio 1989), and descending auditoryinputs (Benson
and Brown 1990; Weedman and Ryugo 1996). The
distalportion of the basal dendrite is excited by the descending
branchof the auditory nerve (Smith and Rhode 1985),
while the soma andproximal dendrites are likely inhibited by vertical
cells (Saint-Marieet al. 1991; Voigt and Young
1980, 1990) and possibly by stellatecells of
the posteroventral cochlear nucleus (PVCN) (Oertel etal.
1990; Zhang and Oertel 1994).
There are several theories regarding fusiform cell function. For
example, strong sideband inhibition may serve to enhancethe
representation of spectral peaks (Rhode and Greenberg
1994)or to extend dynamic range in the presence of noise
(Palmer andEvans 1982). DCN neurons better code the
envelopes of amplitude-modulatedstimuli than do auditory nerve fibers
(Backoff et al. 1999; Kimet al. 1990),
leading to the postulation of a "second axis" thatcodes for
envelope frequency (Kim et al. 1990) or periodicitypitch (Langner and Schreiner 1996). Finally, recent
evidence hasled to the theory that the DCN extracts spectral cues
relevantfor sound localization. The head-related transfer function
(HRTF)of the cat contains a prominent notch whose center frequency
variesbetween 8 and 30 kHz according to the elevation of the sound
source(Musicant et al. 1990; Rice et al.
1992). This frequency rangehas an enlarged representation in
the cat DCN as compared withthe cochlea (Spirou et al.
1993). Type IV units, an importantsubset of DCN
projection neurons, show sensitivity to both thewidth and center
frequency of notches in broadband stimuli (Nelkenand Young
1994; Spirou and Young 1991), as do type III
units ingerbils (Parsons et al. 2001).
The present report describes the physiology and anatomy of 17 intracellularly recorded and labeled fusiform cells from theDCN of
anesthetized gerbils. The fusiform cells in gerbils andcats differ in
their physiological response properties in thedecerebrate preparation.
In particular, the incidence of typeIV units in the gerbil is less
than one-third that reported inthe cat (Davis et al.
1996; Shofner and Young 1985). Antidromicstimulation studies in the cat indicate that at least a portionof the
type IV unit population corresponds to fusiform cells (Young1980). Direct intracellular recording and labeling studies,
however,suggest that gerbil fusiform cells are not type IV units
(Dinget al. 1999). This difference across species in
the response propertiesof an important projection neuron motivates one
aim of this study:to make a detailed quantitative comparison of gerbil
fusiformcell anatomy to that of the cat. Golgi studies in the cat
providea suitable database of anatomical measurements for comparison(Blackstad et al. 1984), including the dimensions of
each dendriticarbor. The anatomical analysis of this study suggests,
in part,that gerbil fusiform cells may be electrotonically more
compactthan those of the cat, and that this difference may account forsome of the observed differences in acoustic responseproperties.
Another issue is that fusiform cells exhibit a variety of response
properties. In the decerebrate preparation, they have typeIII unit and
type IV unit response maps (Ding et al. 1999;
Young1980). In anesthetized preparations, fusiform
cells exhibit pauser/buildup,chopper, or onset discharge patterns,
depending on stimulus conditions(Hancock and Voigt
2002; Rhode et al. 1983; Rhode and Smith
1986;Smith and Rhode 1985). The existence of
such variations must berelated to the complexity of the neural
circuits with which fusiformcells interact. But are the cell-to-cell
differences merely theresult of random "wiring" differences, or do
they reflect underlyingprinciples of organization? This question
motivates a second aim:to make a quantitative comparison of fusiform
cell physiologyand morphology in cats and gerbils. Certain
physiological characteristicswere indeed found to have specific
anatomical correlates. Spontaneousrate (SR) was related to the
disposition of the basal dendrites,input resistance was correlated
with apical dendrite total length,and the discharge pattern at best
frequency (BF) was correlatedwith fusiform cell orientation. It
appears that neighboring fusiformcells may have different
physiological properties and hence differentsignal processing
capabilities by virtue of cell-to-cell variationsinmorphology.
This work represents part of the doctoral dissertation of K. E. Hancock.
Methods
Detailed experimental methods are provided in the companion
paper (Hancock and Voigt 2002). Methods specific to the
analysisof anatomical features are describedbelow.
Position measurements
Cell location was quantified as suggested in Fig.
1. The bottom of the figure
shows a series of coronal sections, one of whichcontains a
hypothetical neuron, indicated by the dark circle.The position
z corresponds to the distance between the cell bodyand
the rostral pole of the nucleus, while L indicates the totallength of the nucleus in the rostral-caudal direction. Near therostral
end of the nucleus, the number of layers typically decreasedfrom three
to two; the section where layering disappeared altogetherwas selected
as the rostral pole.
The section containing the soma is shown rotated at the top of Fig. 1
and illustrates measurements made within the coronalplane. The
position y is the depth along a line perpendicularto the
ependymal surface. The value H is the length of this lineextended to the bottom edge of the nucleus. The position
x isthe length of the arc along the bottom edge measured
from theventrolateral side to the intersection with the line used to
measuredepth. The width W is the total arc length of the
bottom edgemeasured from ventrolateral to dorsomedial. The positions
x,y, and z were normalized
by W, H, and L, respectively, to givethe
relative positions Px, Py, and Pz.
Morphological analysis
The fusiform cells were reconstructed in three dimensions working from cameral lucida drawings using custom-designed software.The dendritic structure was analyzed quantitatively from the reconstructiondata using a set of MATLAB (Mathworks) scripts. Total dendriticlength was computed by approximating each dendrite as a sequenceof small cylinders and summing the cylinderlengths.
Measurements were made individually on each of the apical and basal
arbors. The methods follow those detailed by Blackstadet al.
(1984) and will be described briefly here. The first stepwas
to determine the long axis of the arbor. Blackstad et al.performed
this task manually, whereas in this study an automaticmethod was
adopted that consisted of computing the line betweenthe cell body and
the center of mass of the dendritic terminals.The arbor was then
rotated about its long axis in 1° steps. Ateach step the span of the
arbor perpendicular to the long axiswas computed. The arbor
thickness was defined as the narrowestspan, while the arbor
width was defined as the widest span. Thedegree of planarity was
quantified by computing the width to thicknessratio. The arbor
height was measured as the extent of the arboralong its longaxis.
Results
Geometry of the dendritic arbors
The fusiform cell dendritic arbors were quantified by a series of
measurements inspired by the work of Blackstad et al.
(1984)in the cat and described fully in METHODS.
The results serve asa basis for comparison of the gerbil to the cat
and as a basisfor a subsequent quantitative examination of the
relationshipbetween physiology and anatomy. It is important to note
that Blackstadet al. limited their consideration to the central third
of theDCN and thus avoided effects due to the significant curvatureof
the nucleus at its edges. It was not possible to do likewisein our
case due to the sample size limitations inherent to anin vivo
intracellular survey of thiskind.
The anatomical properties of the apical arbors are summarized in Table
1. Estimates were made of the total
dendritic lengthsby summing the lengths of the individual segments
comprising eachthree-dimensional (3-D) reconstruction. The mean apical
lengthwas 3,359 µm, which is very close to the mean value of 3,212 µmreported by Blackstad et al. (1984) in the cat. The
width andthickness measurements were obtained by rotating the arbor
aboutits long axis to find the widest and narrowest projections,
respectively.Both measures are smaller in the gerbil than in the cat,
althoughthe ratio, which reflects the degree of arbor planarity, is
approximatelythe same in both cases (2.56 in the gerbil, roughly 3 in
the cat).The mean height of the apical arbor, measured parallel to thelong axis, was 157 µm in the gerbil as compared with 267 µm inthe
cat.
Table 2 lists the anatomical properties of the basal dendrites in this study. The mean total length was 1,925 µm, as comparedwith 2,728 µm in the cat. The mean arbor width is smaller in thegerbil (314 µm) than in the cat (392 µm), but the thickness islarger (112 vs. 72 µm). The result is that the width to thicknessratio in the gerbil (3.07) is about half that in the cat (5.70).The mean basal arbor is 250 µm in height as compared with 389 µm in the cat.
Tonotopy
A qualitative illustration of the tonotopic organization is
presented in Fig. 2A, in which
the 17 fusiform cells of this studyhave been mapped onto a single DCN.
Only the basal dendrites havebeen drawn because that is presumably
where fusiform cells receiveacoustic input (Smith and Rhode
1985). The dendrites are colorcoded according to BF, as shown.
Figure 2A qualitatively suggeststhat the gerbil DCN has a
substantial volume devoted to relativelow BFs. The orderly arrangement
of cells by BF is also apparent,with the lowest BFs in the
rostral-most and ventrolateral-mostaspect of the nucleus.
Figure 2A shows that BF increases in both the dorsomedial and caudal directions. This observation is quantified in Fig. 2Bwhere the BF is plotted as a function of the relative X-positions(ventrolateral-to-dorsomedial location) and the relative Z-positions(rostral-to-caudal location) of the fusiform cell somata. Thestraight line fits to these data indicate that BF is indeed highlycorrelated with these twodimensions.
The tonotopic axis is described by the equation log(BF) = 1.45Px + 1.01Pz (r = 0.81, P < 0.001), obtained by performing multiplelinear
regression on log BF using both the relative X- and
Z-positions.A tonotopic position was determined for each
neuron by projectingits location onto this axis and computing the
distance from theorigin (Px = Pz = 0).
The resulting positions are plotted in Fig.3 as a function of BF. For comparison,
the place-frequency mapfor the gerbil cochlea is also plotted, where
position indicatesthe relative distance from the base of the cochlea.
In general,Fig. 3 shows that the spatial distribution of BFs in the
DCN closelyfollows the distribution of characteristic frequencies
(CFs) alongthe cochlea. For comparison, the place-frequency map
computedfor the cat DCN by Spirou et al. (1993) is also
plotted.
Fusiform cell orientation varies with location
Figure 4 summarizes a systematic shift in the orientation of the long axis as a function of rostral-caudal position. In therostral end of the nucleus, the apical dendrites tend to be positionedon the rostral side of the soma while the basal dendrites extendin the caudal direction. Near the center of the DCN, the orientationis roughly vertical (dorsal to ventral). Toward the caudal pole,fusiform cells have caudally directed apical dendrites and rostrallydirected basal dendrites.
It would appear that this trend is a consequence of the shape of the
DCN itself. The DCN can be visualized as a series ofthin shells, with
the molecular layer wrapped around the fusiformcell layer, which in
turn is wrapped around the deep layer. Thusfrom any position within
the fusiform cell layer, the apical dendritesradiate outward to fill
the molecular layer while the basal dendritesconverge inward to occupy
the deep layer. A similar finding wasreported by Rhode et al.
(1983), who further describe the cellsin the rostral end
having more numerous apical dendrites thatmore frequently emerge
directly from the soma. Neither this studynor the previous one finds
any obvious physiological sequellaeto this trend, which possibly is
simply a consequence of the overallcurvature of thenucleus.
Spontaneous rate depends on basal dendrite orientation
The spontaneous discharge rates of the fusiform cells in this sample range from 0 to 54 spikes/s. These can be separated intoa low SR group (rate <2.5 spikes/s, 8/17 cells) and a high SRgroup (rate >7.5 spikes/s, 9/17 cells). The creation of two SRcategories may, in fact, represent an artificial division of acontinuously distributed property, but is useful here as a convenientmeans of visualizing a related anatomical trend. Specifically,there is a correlation between spontaneous rate group and thedisposition of the basal dendrites, as depicted in Fig. 5. Thebasal dendrites of the low SR cells (top row) are primarily directedcaudally away from the soma. The high SR cells (bottom row) tendalso to have branches oriented in the rostral direction, givingthe distribution of the basal dendrites a more symmetrical appearance.
These observations were put on a more quantitative basis by computing
the centroid of each basal arbor with respect to thesoma. The trend is
specifically captured by the rostral-caudalcomponent,
ZC, as shown in Fig. 5. Note that the
value of ZC ispositive for positions
caudal to the soma. For every low SR cell(ZC 
63.2 µm), the basal arbor
centroid is caudal to that ofevery high SR cell
(ZC 
48.8 µm). No correlation was
found betweenthe absolute position of the basal arbor centroid and
spontaneousactivity.
The nine cells shown in Fig. 5 come from the same general region of the DCN, reflected by the similarity of their best frequencies.This is an important consideration when examining the arrangementof the basal dendrites, because as described above, the orientationof the fusiform cell long axis changes as a function of position(Fig. 4).
Input resistance is a function of total apical dendritic length
Figure 6 shows that fusiform cell
input resistance is correlated with apical dendritic length, but not
with basal dendriticlength. The best line fit to the apical length was
computed afterremoving the two points indicated by triangles in Fig.
6A. Thecorrelation with apical length is negative, so that
larger lengthscorrespond to smaller resistances. This is consistent
with a passivemodel in which membrane conductance is proportional to
surfacearea, insofar as dendritic surface area is proportional to
totallength. Input resistance was not correlated with the sum of theapical and basal lengths (r = 
0.06). The presence of
spines,however, greatly increases the surface area per unit length ofthe apical dendrite and so a simple sum of total lengths probablyunderstates the contribution of the apical dendrite to the
overallpassive membrane conductance. We did not consider the effectsof surface area more directly because of difficulties estimatingit
that arose from inconsistencies in the quality of spine labeling.
Regularity histogram shape depends on orientation of apical arbor
Regularity histogram shapes were quantified using three slope
measurements as described in the companion paper. Briefly, thetransient slope, mT, most closely
follows the classification schemeof Gdowski (1995). It
is particularly sensitive to the changein interspike interval over the
initial 5-10 ms of response andsince nearly all of the cells in this
study had decreasing intervalsover this range, regardless of their
subsequent behavior, thetransient slope was not necessarily an
effective means of characterizingrate trends over the entire stimulus
duration. To better capturethese rate trends, the slope measurements
m1 and
m2 were computedby performing a
two-line fit to the interspike interval data afteromitting the
firstbin.
Figure 7 shows that for the 10 fusiform
cells with BFs less than 2 kHz, the slope
m1 is correlated with the orientation
ofthe apical dendrites. The angle 
apical
corresponds to the rotationrequired to find the narrowest dendritic
profile after makingthe long axis of the arbor vertical. A value of
zero correspondsto an arbor oriented perpendicular to the coronal
plane. The apicaldendrites in Fig. 7 are drawn looking down on their
tops, suchthat their long axes project out of the page. The values of
m1have been divided into three
groups: high, medium, and low, indicatedin Fig. 7 by circles,
triangles, and squares, respectively. Thedata indicate that the
fusiform cells with apical arbors orientedmost nearly perpendicular to
the coronal plane have the most positivem1 values (circles), while those
oriented closest to parallelto the coronal plane have the most
negative m1 values (squares).
Correlation of cell properties with location
An effort was made to identify fusiform cell characteristics that vary systematically with location. To do this, a wide varietyof physiological response metrics (see companion paper) were systematicallycorrelated with the normalized X-, Y-, and Z-position measurements(see METHODS).
Two statistically significant trends were identified, roughly orthogonal to the tonotopic axis. The relative noise index decreasedin the X-direction (ventrolateral to dorsomedial), meaning thatthe responses to noise became progressively weaker in this direction(Fig. 8A). A gradient in wideband inhibitory strength is sufficientto account for this observation, as detailed in the DISCUSSION.The second trend was that input resistance also tended to decreasein the X-direction (Fig. 8B). This is consistent with the factthat total apical dendritic length increases in the same direction(Fig. 8C), since the inverse relationship between these two propertieshas already been described.
Aside from tonotopy, the only statistically significant spatial trends were found in the X-direction. Since neither trendwas accompanied by a significant dependence on Z-position, itwas not possible to compute an axis trajectory for quantitativecomparison with the tonotopic axis computed above. It can, however,be said that while best frequency is strongly correlated withboth X- and Z-position, input resistance and relative noise responseare strongly correlated only with X-position. So, although theseresults cannot resolve the issue of an orthogonal axis per se,there is at least a qualitative suggestion that the spatial gradientsof these two properties are not parallel with the frequencyaxis.
Discussion
A detailed quantitative examination of fusiform cell physiology and anatomy was made in this study. The following findingswill be discussed. 1) The basal dendrite in the gerbil is shorterthan in the cat. 2) The gerbil DCN appears to lack the high-frequencyspecialization of the cat DCN. 3) High spontaneous firing ratesare correlated with basal dendrites having both rostrally andcaudally directed branches, while low spontaneous rates are correlatedwith basal dendrites having only caudally directed branches. 4)The inhibition reflected in the slope of the regularity histogramis related to the orientation of the apical arbor. 5) Noise responsestrength appears to be systemically organized within an isofrequencysheet.
Consideration of the basal arbor total length
The basal dendrites in the gerbil have about 70% the total length
that they do in the cat and thus may be electrotonicallymore compact.
The equivalent cylinder model for a dendritic arborhas a
characteristic electrotonic length, which is proportionalto the ratio
of the physical length of the cylinder to the squareroot of its
diameter (Rall 1977). Consider a hypothetical catfusiform cell that has three primary basal dendrites giving riseto
identical branching structures. One possibility is that the"gerbil" fusiform cell retains all three branches, but each branchis shortened by a third. The equivalent cylinder for such a cellwould
be physically shorter than its counterpart in the cat, buthave the
same diameter and hence a shorter electrotonic length.A gerbil
fusiform cell could also be produced by removing oneof the three
hypothetical branches, giving the observed one-thirdreduction in total
length. The equivalent cylinder would havethe same physical length as
the cat fusiform cell, but its diameterwould be smaller, resulting in
a longer electrotoniclength.
Which case best represents the actual situation? Blackstad et al. did not report branch order statistics for the cat, so itis not possible to make a comparison in this regard. But, as shownin Table 2, the height of the basal arbor is about one-thirdsmaller in the gerbil than in the cat. This would seem to rejectthe second scenario above, since the pruning of one branch wouldnot affect the size of the remaining branches and hence the arborheight should remain about the same. This leaves the first scenarioas the most viable and suggests that the effect of dendritic shorteningin the gerbil is to make the basal arbor electrotonically morecompact than in thecat.
Assuming that inputs from the auditory nerve are distributed toward the
distal ends of the basal dendrites (Smith and Rhode1985), a possible effect of this electrotonic shortening wouldbe to decrease the attenuation of excitatory synaptic potentials.To
the extent that inhibitory inputs are received at more proximallocations (Berrebi and Mugnaini 1991; Saint-Marie
et al. 1991),they are relatively unaffected by the overall
length of the dendrite.Hence, an electrotonically more compact basal
dendrite might preferentiallyenhance excitatory drive relative to
inhibition. Indeed, previousresults suggest that the proportion of DCN
units having type IVunit properties is smaller in the gerbil than in
the cat (11%vs. 32-45%) and the proportion of type III units is
larger (62%vs. 23%) (Davis et al. 1996). Ding
et al. (1999) reported on 13 labeled fusiform cells from the
decerebrate gerbil, none of whichhad classic type IV unit response
properties. Interestingly, thetype IV unit incidence in rabbit (23%)
and chinchilla (25%) appearsto follow the same size-related trend
(Davis et al. 1996; Huiand Disterhoft
1980; Kaltenbach and Saunders 1987).
This species-related difference in unit incidence was considered by
Davis and Voigt (1996) using a point neuron model. Theirhypothesis was that a weakened contingent of type II unit inhibitiononto DCN projection neurons was responsible for the lack of typeIV
units found in the gerbil relative to the cat. They showedthat a
40-50% reduction in the number of type II unit inputs wassufficient
to turn a model type IV unit into a type IV-T or typeIII unit. A
hypothesis based on the present finding in regardto basal dendrite
length, in contrast, suggests that the balanceis shifted toward
excitation by an enhancement of the excitatoryinputs, rather than by a
reduction of the inhibitory inputs. Theseissues might effectively be
explored using a compartmental modelof a fusiformcell.
Tonotopic organization of the gerbil DCN
The qualitative picture of tonotopy presented in Fig. 2 agrees
well with the description of frequency organization in gerbilDCN
obtained using measurements of 2-deoxyglucose uptake (Ryanet
al. 1982). On a more quantitative basis, the fusiform cellBFs
were plotted in Fig. 3 as a function of the cell positionalong the
tonotopic axis. The data plotted in this manner correspondwell with
the cochlea place-frequency map determined by Müller(1996) in the Mongolian gerbil (Fig. 3). Such quantitative
correspondencebetween frequency representation in the cochlea and
tonotopicorganization in central auditory structures is frequently
observed(Müller 1990).
A notable exception is the cat DCN, whose representation of the 8- to
30-kHz range is disproportionately larger than the representationof
the same frequency range in the cochlea (Spirou et al.
1993).The head-related transfer function (HRTF) in the cat
containsspectral notches that may serve as cues for determining soundsource elevation (Rice et al. 1992). These notches fall
in the8- to 30-kHz range, suggesting that the enhanced representationof these frequencies in the cat DCN is a functional specializationrelated to coding those particular spectral features (Spirou etal. 1993).
The place-frequency analysis shown in Fig. 3 is limited to the extent
that it is a one-dimensional description of the tonotopy;it does not
consider variations in cell density or the possibilityof a
two-dimensional frequency gradient. The comparison with thecat data of
Spirou et al. (1993) is appropriate insofar as thecat
data are also based on a one-dimensional frequency axis. Thatstudy,
however, was based on BF estimates made at finely spacedlocations from
a large number of electrode tracks. Furthermore,Spirou et al.
(1993) accounted for variations in fusiform celldensity when
drawing conclusions about BF representation in theDCN.
The present data therefore should be regarded as preliminary but appear to underscore the fact that the tonotopy of the gerbilDCN (and cochlea) is largely devoted to a lower frequency range.Frequencies below 10 kHz occupy about 60% of the length of bothstructures, and no specialized frequency representation in thegerbil DCN is apparent. It is currently unknown whether or notthe gerbil HRTF contains spectral elevation cues similar to thoseidentified in the cat HRTF. Measurements of the HRTF in gerbiland a more detailed examination of frequency representation inthe DCN are essential to a comparative evaluation of DCN functionin the twospecies.
Spontaneous rate
The results indicate that the disposition of the basal dendrites is correlated with spontaneous rate for the fusiform cellswith best frequencies less than 2 kHz. The basal dendrites oflow SR cells are directed away from the soma only in the caudaldirection, while the high SR cells have basal dendrite branchesextending both rostrally and caudally. The basal arbors of thelow SR units, relative to those of the high SR units, have morecaudally located centroids. It is important to note that thisobservation is based on relative comparisons of basal arbor structureamong cells having similar orientations. No absolute metric wasfound to allow for a global quantification of the relationshipbetween SR and basal dendrite position. It was thus necessaryto limit consideration to this BF range because of the generalshift in long axis orientation with rostral-caudal position (andhence BF) and because there were not sufficient numbers in anyother frequency band for cell-to-cell comparisons to bemade.
It is not immediately clear how the orientation of the basal dendrites
may influence spontaneous activity. Liberman
(1993)suggested that auditory nerve inputs to the cat
DCN may be segregatedbased on spontaneous rate, with the high SR
fibers terminatingdeeper in the nucleus than the low SR fibers. This
appears tobe inconsistent with our results, since the rostrally
directedbasal dendrites of the high SR fusiform cells tend to be moreshallow in depth than the caudally directed branches common toboth SRgroups.
Another possibility is that the rostrally directed branches access some other set of inputs that modulate spontaneous activity.It also may be that the orientation characteristic of the highSR cells has electrotonic consequences that emphasize excitatoryinputs over inhibitory inputs. Regardless of the mechanism, theresults suggest that the distribution of fusiform cell spontaneousactivities is not entirely due tohappenstance.
It is difficult to say what functional consequences may arise from
having a subset of the fusiform cell population preferentiallyreceive
low SR input. It has been suggested that low SR auditorynerve fibers
are recruited to improve intensity discriminationat high sound levels
or are useful for signal in noise problems(Viemeister
1983). Extending such interpretations to the DCN isproblematic, because they are based on the fact that low SR ANfibers typically have high acoustic thresholds (Liberman
1978),a trend not generally characteristic of DCN units. It
has beenshown that low SR AN fibers better synchronize to AM tones
(Jorisand Yin 1992), but there remains disagreement
over the generalsuitability of DCN projection neurons for encoding
such stimuli(Joris and Smith 1998).
Shape of regularity histogram
For the fusiform cells in the 0- to 2-kHz band, a correlation was
observed between the orientation of the apical dendriticarbor,
quantified by the rotation, apical, about the
long axisyielding the narrowest projection of the arbor, and the shapeof the regularity histogram, as quantified by the slope,
m1 (Fig.7). The slope values
m1 and
m2 are obtained by simultaneouslyfitting two lines to the interspike interval plot after omittingthe
first bin. For the data of this study, the value of
m1 appearsto be a more useful measure
of inhibition than the monotonicityof the BF rate-level curve, because
the m1 values are more evenlydistributed over a wider interval. A positive value of
m1 reflectsa rate trend similar to
the underlying excitatory drive from auditorynerve fibers and hence
suggests relatively weak inhibitory input.Negative values are taken as
an indication of a relatively strongerinhibitorycontribution.
One interpretation of this result is that the apical dendrite
orientation determines the cross-sectional area of the arborperpendicular to the trajectory of the parallel fibers and henceaffects the pattern of activity in the apical arbor. For example,those
presenting a narrow face to the parallel fiber network maybe more
strongly influenced by inhibitory inputs from the cartwheelcell
population. Although cartwheel cells are known to be acousticallyresponsive, their activity is relatively weak and of high threshold(Ding et al. 1999; Parham and Kim 1995)
and would not be expectedto account for the relatively strong
inhibition represented bynegative values of
m1.
A second possibility is that since the neurons represented in Fig. 7
come from the ventrolateral third of the nucleus, thechange in apical
arbor orientation may result from curvature ofthe strial axis in this
region (Blackstad et al. 1984). In thiscase, the
variations in orientation and in slope
m1 may, in fact,be functions of
position. That no such dependence was apparentin our position data may
indicate limitations in the accuracyof mapping position across
different tissuesamples.
Possible significance of physiology-morphology correlations
Figures 5-7 demonstrate that certain morphological features are correlated with specific physiological properties. The geometriesof the apical and basal arbors influence input resistance andspontaneous activity, respectively, while some aspect of cellorientation apparently contributes to the inhibition measuredin the regularity histogram. It is thus possible that fusiformcells along the isofrequency axis have graded physiological properties,and hence different signal processing characteristics. In thisway, the fusiform cell population might be capable of performingdifferent operations on the same set ofinputs.
A chance example from the present study illustrates that significant morphological differences may indeed exist between nearbycells. Figure 9 is a sagittal view of two fusiform cells, labeledin a single electrode track, their cell bodies separated by lessthan 10 µm. They were located in the caudal DCN, and hence, asdescribed earlier, their long axes have a rostral-to-caudal orientation.The apical arbor of the black-colored neuron is sparser than thatof the gray-colored neuron. Furthermore, the two basal arborsdo not overlap completely, but follow slightly different trajectories.The results of Fig. 9 support the notion that neighboring fusiformcells might have markedly different morphologies.
Organization of sensitivity to broadband noise
The notion that the DCN contains a functional axis orthogonal to
the frequency axis is suggested by anatomical features. First,there is
the network of parallel fibers oriented perpendicularto the underlying
auditory nerve fibers. If systematic variationsin activity within the
parallel fiber network contribute to thevariations in fusiform cell
physiology, then fusiform cell propertiesmight vary in a spatially
dependent manner. Another anatomicalsubstrate for a second axis in the
DCN is a progressive decreasein the number of vertical cells in the
dorsomedial direction withinthe coronal plane (Lorente de
Nó 1981). Since vertical cellspresumably inhibit
fusiform cells, the magnitude of inhibitoryresponse features (tone
slope, interspike interval slope, etc.)should also decrease in the
dorsomedialdirection.
The results show that the relative noise index is negatively correlated
with position in the ventrolateral to dorsomedialdirection (Fig.
8A). In other words, fusiform cell responses tonoise tend
to become weaker in the same general direction in whichLorente
de Nó (1981) reported the vertical cell layer becomingthinner. A decrease in the number of vertical cells, however,represents a loss of inhibition and so cannot account for thediminishing noise responses. The noise sensitivity of DCN principalcells is thought to be shaped by a source of wideband inhibition,possibly originating in the PVCN (Nelken and Young
1994). Theobserved noise responses in the current study might
be accountedfor by an increasing contribution of this inhibitory
source inthe dorsomedialdirection.
Earlier studies have identified two inhibitory components to the
response maps of type IV units, as schematized in Fig.
10.The first arises from a band of
type II units, centered belowthe BF of the type IV unit (Voigt
and Young 1990), while the secondcomponent, wideband
inhibition, possibly arises from the PVCNand is centered above the
type IV unit BF (Nelken and Young 1994;Spirou
and Young 1991). This organization might be consistentwith
wideband inhibitory input strengthening in the dorsomedialdirection,
as suggested by the present results, and the verticalcell layer
thinning in the same direction, as described by Lorentede Nó.
If, for example, each type IV unit receives input froma band of type
II units (presumably vertical cells) centered spatiallyon BF, then the
resulting inhibitory band would have a lower BFbecause the vertical
cells are more dense in that direction. Similarly,if the wideband
inhibition is stronger in the dorsomedial direction,inhibition from a
band spatially centered on BF will itself havea higher BF. The idea
that these two inhibitory sources mighttrade for one another across
the width of the DCN is consistentwith data presented by Nelken
and Young (1994). Their Fig. 8Bsuggests that the
influence of inhibition by type II units, asmeasured by the maximum
driven BF rate, is negatively correlatedwith the influence of wideband
inhibition, as measured by theminimum inhibitory notch width.
Conclusion
This report has described differences between cats and gerbils in the anatomical properties of DCN fusiform cells and in theirtonotopic arrangement. The report also described systematic distributionsof functional properties within the fusiform cell population.How such variations contribute to DCN function is yet to beunderstood.
Miscellaneous
ACKNOWLEDGMENTSWe thank committee members H. S. Colburn, L. H. Carney, M. C. Liberman, and A. M. Berglund for helpful comments and suggestions. We also thank D. Oertel for comments and P. Patterson for processing some of the tissue.
K. E. Hancock was supported by a fellowship from The Whitaker Foundation. This work was funded by Grant DC-01099 from the National Institute on Deafness and Other Communication Disorders.
Present address of K. E. Hancock: Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02114.
FOOTNOTES
Address for reprint requests: H. F. Voigt, Dept. of Biomedical Engineering, Boston University, 44 Cummington St., Boston, MA 02215-2407 (E-mail: [email protected]).
Received 27 April 2001; accepted in final form 20 December 2001.
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Table 1
| Table 1. Properties of apical dendritic arbors | |||||
|
|
|||||
| Cell | TL, µm | Width, µm | Thickness, µm | Ratio | Height, µm |
|
|
|||||
| 95026 | 2,539 | 195 | 118 | 1.66 | 117 |
| 95055 | 3,465 | 344 | 99 | 3.47 | 119 |
| 95082 | 2,138 | 235 | 97 | 2.42 | 185 |
| 95135 | 3,290 | 297 | 121 | 2.45 | 168 |
| 97002 | 3,097 | 283 | 180 | 1.57 | 144 |
| 97005a | 3,541 | 369 | 61 | 6.05 | 206 |
| 97008b | 2,410 | 219 | 93 | 2.35 | 102 |
| 97022a | 4,294 | 323 | 104 | 3.10 | 147 |
| 97054a | 4,068 | 346 | 93 | 3.74 | 179 |
| 97054b | 3,228 | 341 | 100 | 3.43 | 216 |
| 97055a | 2,554 | 146 | 104 | 1.41 | 233 |
| 97072a | 6,435 | 373 | 173 | 2.15 | 137 |
| 97073 | 3,348 | 226 | 121 | 1.86 | 157 |
| 98001 | 2,843 | 214 | 167 | 1.28 | 123 |
| 98012a | 2,327 | 218 | 87 | 2.51 | 151 |
| 98014 | 3,238 | 243 | 93 | 2.61 | 135 |
| 98024a | 4,289 | 294 | 203 | 1.45 | 154 |
| Mean | 3,359 | 274 | 118 | 2.56 | 157 |
| Cat mean | 3,212 | 354 | 138 | ~3 | 267 |
|
|
|||||
| TL, total length. | |||||
Table 2
| Table 2. Properties of basal dendritic arbors | |||||
|
|
|||||
| Cell | TL, µm | Width, µm | Thickness, µm | Ratio | Height, µm |
|
|
|||||
| 95026 | 636 | 178 | 34 | 5.28 | 187 |
| 95055 | 3,359 | 301 | 137 | 2.20 | 563 |
| 95082 | 1,776 | 325 | 85 | 3.81 | 368 |
| 95135 | 5,600 | 515 | 274 | 1.88 | 318 |
| 97002 | 1,788 | 297 | 119 | 2.50 | 282 |
| 97005a | 1,191 | 240 | 143 | 1.68 | 157 |
| 97008b | 1,658 | 314 | 75 | 4.19 | 227 |
| 97022a | 1,490 | 389 | 106 | 3.67 | 182 |
| 97054a | 1,704 | 191 | 58 | 3.31 | 210 |
| 97054b | 941 | 248 | 119 | 2.09 | 118 |
| 97055a | 1,391 | 318 | 86 | 3.71 | 80 |
| 97072a | 1,047 | 264 | 79 | 3.34 | 288 |
| 97073 | 1,236 | 235 | 80 | 2.94 | 316 |
| 98001 | 3,196 | 538 | 180 | 2.99 | 356 |
| 98012a | 3,443 | 529 | 150 | 3.52 | 173 |
| 98014 | 1,371 | 242 | 89 | 2.72 | 220 |
| 98024a | 897 | 218 | 95 | 2.30 | 205 |
| Mean | 1,925 | 314 | 112 | 3.07 | 250 |
| Cat mean | 2,728 | 392 | 72 | 5.70 | 389 |
|
|
|||||
| TL, total length. | |||||
Figures
Figure 1 Summary of position measurements. |
||
Figure 2 Tonotopic organization of the gerbil dorsal cochlear nucleus (DCN).
A: the basal dendrites of the 17 fusiform cells from
this study mapped onto a single DCN. A patch has been removed from the
surface of the DCN to show the interior. Dendrites are color-coded
according to best frequency (BF) as shown. D, dorsal; R, rostral; L,
lateral. B: scatterplots showing BF vs. relative
X-position (top) and relative
Z-position (bottom). Regression line for
X-position given by log(BF) = 2.38x |
||
Figure 3 Comparison of frequency-place maps for the gerbil cochlea and DCN.
Place-frequency data for fusiform cells obtained by projecting soma
locations onto frequency axis computed in the text. Place-frequency map
for the gerbil cochlea from Müller (1996) |
||
Figure 4 Fusiform cell orientation changes with rostral-caudal position. DCN is represented by a series of coronal slices. Arrows point from soma locations to renderings of fusiform cells in a sagittal view. Thick gray lines indicate the long axis of each cell. D, dorsal; C, caudal. |
||
Figure 5 Spontaneous activity and basal dendrite arrangement. Neurons are from the 0- to 2-kHz region and are drawn in a parasagittal view. Apical dendrites are shown in gray; basal dendrites in black. Basal dendrites of low spontaneous rate (SR) cells (top row) are oriented primarily in the caudal direction. Those of the high SR cells (bottom row) have both rostrally and caudally directed branches. This difference is quantified using the parameter ZC, which is the rostral-caudal component of the basal arbor's centroid, measured with respect to the soma. The low SR units have larger ZC values (centroids located more caudally) than the high SR units. |
||
Figure 6 Relationship between input resistance and arbor length.
A: input resistance is highly correlated with apical
dendrite length. Regression line: y = |
||
Figure 7 Relationship between regularity histogram shape and orientation of
apical arbor. Top: slope m1
from the regularity histogram plotted vs. the orientation of the apical
arbor. The orientation |
||
Figure 8 Physiological properties correlated with position. Relative noise index
(A) and input resistance (B) are
negatively correlated with position in the X-direction.
Regression line for noise index: y = |
||
Figure 9 Two neighboring fusiform cells from the caudal end of the DCN. Long axes are nearly horizontal in accordance with the general rostral-caudal shift in orientation. At the top, the cells are drawn in their correct relative positions. At the bottom, they are drawn separately to show individual details clearly. |
||
Figure 10
Inhibitory components of a type IV unit response map. Gray, inhibition
from type II units that probably correspond to vertical cells. The peak
of this inhibitory area is typically below the BF of the type IV unit.
Lorente de Nó (1981) |
3x +1.30, r = 
