Department of Physiology, Monash University, Monash, Victoria 3800, Australia
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ABSTRACT |
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Rajan, R.. Unilateral Hearing Losses Alter Loud Sound-Induced Temporary Threshold Shifts and Efferent Effects in the Normal-Hearing Ear. J. Neurophysiol. 85: 1257-1269, 2001. In animals with bilaterally normal hearing, olivocochlear pathways can protect the cochlea from the temporary shifts in hearing sensitivity (temporary threshold shifts; TTSs) caused by short-duration intense loud sounds. The crossed olivocochlear pathway provides protection during binaural loud sound, and uncrossed pathways protect when monaural or binaural loud sounds occur in noise backgrounds. Here I demonstrate that when there is a chronic unilateral hearing loss, effects of loud sounds, and efferent effects on loud sound, in the normal-hearing ear differ markedly from normal. Three categories of test animals with unilateral hearing loss were tested for effects at the normal-hearing ear. In all categories a monaural loud tone to the normal-hearing ear produced lower-than-normal TTSs, apparently because of a tonic re-setting of that ear's susceptibility to loud sound. Second, in the two test categories in which the hearing-loss ear was only partly damaged, binaural loud sound exacerbated TTSs in the normal-hearing ear because it caused threshold shifts that were a combination of "pure" TTSs and uncrossed efferent suppression of cochlear sensitivity. (In normal cats, this binaural tone results in crossed olivocochlear protection that reduces TTS.) Binaural loud sound did not produce such uncrossed efferent effects in the test category in which the nontest ear had suffered total hearing loss, suggesting that this uncrossed efferent effect required binaural input to the CNS. It is noteworthy that, in the absence of this uncrossed efferent suppression, the pure loud sound-alone induced TTSs after binaural exposure were low. Thus in the absence of any efferent effect, the normal-hearing cochlea had a reduced susceptibility to loud tone-induced damage. Finally, the results suggest that, with respect to cochlear actions at high sound levels, uncrossed and crossed efferent pathways may exert different effects at the one type of receptor cell.
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INTRODUCTION |
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The mammalian cochlea receives a
dual-component efferent innervation from the brain stem (e.g.,
Aschoff and Ostwald 1987; Aschoff et al.
1988
; Guinan et al. 1983
; Liberman et al.
1989
; Robertson et al. 1987
;
Thompson and Thompson 1986
; Warr et al. 1986
). The lateral olivocochlear system (LOCS), almost
exclusively from only the ipsilateral lateral superior olivary nucleus,
terminates on dendrites of afferent neurons. The medial olivocochlear
system, from ipsilateral (uncrossed MOCS, UMOCS) and contralateral
(crossed MOCS, CMOCS) periolivary nuclei, terminates on outer hair
cells (OHCs).
Physiological activation of the efferent pathways by sound can reduce
the temporary cochlear desensitization (temporary threshold shifts;
TTSs) caused by loud tones (Cody and Johnstone 1982;
Handrock and Zeisberg 1982
; Rajan 1992
,
1995a
,b
, 1996b
; Rajan and
Johnstone 1988a
,b
). Monaural loud tones in a background
of silence serve as a baseline against which such protective effects
can be demonstrated, since such conditions do not activate efferent
activity that modulates TTSs (Rajan 1988a
,
1992
, 1995a
,b
, 2000
).
Then, binaural loud tones activate CMOCS input to the OHCs to reduce
TTSs, protecting the cochlea (Rajan 1992
,
1995b
, 1996a
, 2000
;
Rajan and Johnstone 1988a
). Uncrossed efferent pathways
protect (Rajan 2000
) when a loud tone is presented in a
background of noise at 60 dB SPL or greater. Unlike the CMOCS effect,
protection exerted by uncrossed efferents does not require binaural
stimulation but occurs as long as the tone is presented in a background
of noise. The uncrossed pathway consists of the LOCS pathway
terminating on dendrites of afferent neurons and the UMOCS pathway
terminating on OHCs. For parsimony of explanation, the protective
effects of uncrossed pathways have been attributed (Rajan
2000
) to efferent terminations on OHCs, i.e., to the UMOCS
pathway. As well (Rajan 2000
), it is difficult to see
how effects on dendrites of afferent neurons (exercised by the LOCS)
could prevent noise exacerbation of the loud tone-induced TTSs. In this
context it is worth noting that the above-cited studies of protection
measured post-loud sound effects 5 min after loud sound. At this
postexposure time, the major, if not sole, contribution to TTSs appears
to be damage exercised at OHCs (Patuzzi et al. 1989
),
and it has been shown (Rajan 1996a
) that protective effects measured at this time are totally commensurate with effects predicted to occur only at OHCs (Patuzzi et al. 1989
;
Rajan and Patuzzi 1992
). Thus with such postexposure
measurements, discussion of any changes must focus on effects exercised
at the OHCs.
The CMOCS protection from TTSs seen when loud tones are presented
binaurally also occurs to successive loud tone exposures presented with
a short inter-exposure measurement interval (Rajan 1996a). Thus in normal animals CMOCS protection is quite robust and can be demonstrated even after hearing losses are created acutely
by a first exposure. (It is not yet known whether this also applies for
the uncrossed pathway protection of the cochlea from TTSs caused by a
loud tone in a background of noise.) However, during the experiments on
CMOCS protection (Rajan 1995a
,b
, 1996a
), a chance observation was that when animals had unilateral
chronic hearing losses, quite different and remarkable cochlear
efferent effects were obtained in the normal hearing ear to
testing with loud tones in silence. These effects were explored in
detail and form the basis of the present report.
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METHODS |
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Animal treatment and measurement of hearing sensitivity
Procedures for anesthetization and treatment of test cats were
as reported (Rajan 1995a,b
, 1996a
) for
concurrently tested cats that provide comparison normative data here.
Adult cats (3-6 kg) were tested under procedures approved by the
Monash University Standing Committee on Ethics in Animal
Experimentation and conforming to guidelines of the National Health and
Medical Research Council of Australia. Cats were anesthetized (60 mg/kg
ip) with pentobarbital sodium (Nembutal) and maintained with
intravenous doses amounting to Nembutal at 2-3 mg · kg
1 · h
1. Depth
of anesthesia was monitored through continuous recording of rectal
temperature, the electrocardiographic (ECG) and
electromyographic (EMG) activity from forearm muscles, and
regular hourly checks of responses to noxious forepaw pinching, of the
presence of pupillary dilatation and the absence of corneal reflexes.
The ECG/EMG electrodes' output was displayed on an oscilloscope and
fed into a speaker for continuous monitoring of the cat's condition
and depth of anesthesia. Body temperature was maintained at 37.5 ± 0.5°C by a thermostatically controlled warming blanket, regulated
by feedback from a rectal probe. Cats were tracheostomized but allowed
to breathe independently (Rajan 1995a
,b
,
1996a
).
The tympanic bullae were exposed (Rajan et al. 1991) and
stainless steel electrodes implanted against the round window of both
cochleas. A fine bore plastic tube was inserted into the bulla hole
adjacent to the electrode, to ventilate the middle ear, and the holes
sealed with dental cement. The meatuses were transected to place sound
delivery tubes close to the tympanum.
Hearing sensitivity was assessed by measuring thresholds for the
auditory nerve compound action potential (CAP) at frequencies from
1-40 kHz (Rajan 1995a; Rajan et al.
1991
), using pure tone bursts (10-20 ms duration, 1-ms
rise-fall times) presented at a rate of 7-8/s. The CAP, recorded from
the round window electrode, was amplified ×1,000 and band-pass
filtered (300 Hz to 10 kHz) before being displayed on an oscilloscope.
Threshold criterion was a visually just-detectable CAP response on the
oscilloscope; such visual detection thresholds (VDTs) correspond to a
CAP amplitude of about 1-2 µV (see Rajan et al.
1991
).
Tones to each ear were generated independently by one of two channels
of a digital synthesis system, gated under computer control and passed
into separate computer-controlled attenuators. Each attenuator fed
separately into an electronic mixer box that allowed manual switching
of sound delivery to either of two output channels. Cross talk between
mixer box channels was greater than 100 dB up to 10 kHz,
100 dB
from 10-20 kHz, decreasing thereafter to
95 dB at 40 kHz. Each
output channel lead to a Stax speaker in specially designed housing
with a sound delivery tube leading from the speaker into the external
auditory meatus (Rajan et al. 1991
).
The majority of experiments in test cats (see Classification of
animals) was completed in one laboratory over a 4-yr
period using the above procedures. (The long time span was due to the fact that the occurrence of 2 categories of test cats was a random process not controlled experimentally.) Three cats were tested in more
recent experiments in a new laboratory (Rajan 2000) with cats being artificially ventilated on room air and maintained with
continuous infusion of anesthetic, and sound being delivered through
Sennheiser HD 535 speakers. Effects were identical to those seen
previously in the same test category (see Classification of
animals) tested in the same way. Hence these cats are not
differentiated from others of that same category tested in the same manner.
Classification of animals
CAP thresholds in each cat were compared with normative data
(Rajan 1995a; Rajan et al. 1991
). The
normal hearing group of animals, which provides data (Rajan
1995a
,b
, 1996a
) for comparisons, had bilaterally
normal hearing sensitivity from 1-40 kHz. In test groups here, cats
had a unilateral hearing loss, with the other ear having normal hearing
sensitivity (i.e., CAP thresholds within ±1.96 SD of mean normative
thresholds; the statistically normal range, at
= 0.05, by
Student's t-test). Test groups were categorized according
to the etiology of the unilateral hearing loss.
In one test category [idiopathic hearing loss (IHL), n = 27] the etiology of the unilateral hearing losses, present at
initial measurement of hearing in these acute experiments, was unknown. It is presumed that these losses were chronic and possibly due to loud
sound, but it was not possible to obtain enough information from the
university breeding or supply services to determine their cause. In
another test category ("Cyst-HL," n = 13), animals
were also not pretreated. However, during cochlear surgery in the acute experiments here, it was found that only one ear had a
cholesteatoma-like highly vascular cyst completely filling the middle
ear cavity. The cyst had eroded the tympanum and ossicles and had grown
deep into the cochlea through the oval (and often round) window,
resulting in a total hearing loss in that ear (see
RESULTS). In the final test category [chronic
mechanical-lesion hearing losses (CMHL), n = 9],
designed on the basis of early observations in the other two
categories, chronic unilateral hearing losses were induced in
normal-hearing cats by mechanical lesion of the basilar membrane (BM)
using procedures (generally, but not always, of the left cochlea)
described previously (Rajan et al. 1993). Briefly, under acute anesthesia, CAP thresholds were measured to confirm normal hearing sensitivity. Then a lesion was made with a glass micropipette into the most-apical part of the BM visible through the round window
(see Rajan et al. 1993
). Animals recovered for periods from 2.5 to 5.5 mo, in holding rooms in which other cats were also
housed but from which loud noise was precluded, before the terminal experiment.
Different groups of animals in one of the three test categories were tested for the effects of loud sound in the normal-hearing ear, with monaural or binaural exposure being used. In some groups, brain stem lesions were made (see Surgical inactivation of cochlear efferent pathways) to all cochlear efferent pathways or, in one IHL test group, to only the crossed efferent pathways. In total, 12 test groups (5 IHL, 4 CMHL, and 3 Cyst-HL test groups) were tested as detailed in RESULTS.
Surgical inactivation of cochlear efferent pathways
Inactivation of various components of efferent pathways to the
test (normal-hearing) cochlea was made using surgical lesions at the
floor of the fourth ventricle, after removing the overlying cerebellum
(Rajan 1995a). Because of the coursing of cochlear efferent fibers, from this location it is possible to lesion all efferents to one or both cochleas, or crossed pathways to both cochleas
(Warren and Liberman 1989a
) but not lesion only
uncrossed pathways to a cochlea. To totally de-efferent the test
cochlea, a lesion was made 1.5-2 mm lateral of the midline and on the
brain stem side ipsilateral to that cochlea (Rajan
1995a
,b
). To cut only crossed pathways (bilaterally), a midline
lesion was made (Rajan 1995a
,b
). Lesions were always
6-8 mm long, extending about the facial colliculi, identifiable on the
floor of the fourth ventricle. Postmortem histology, occasionally
combined with histochemical staining for acetylcholine esterase (which
stains the efferent pathways), was used to confirm the location of the
cuts (Rajan 1995a
; Warren and Liberman
1989a
).
In all animals with brain stem lesions, prelesion checks were made of the CAP audiogram, heart rate, ECG waveform, and body temperature, and these were re-checked immediately postlesion.
Traumatic loud sound exposures and measurement of cochlear desensitization
The traumatic sound to cause TTS was an 11-kHz tone at 100 dB
SPL for 10 min, chosen as it was the standard loud sound (Rajan 1995a) in a series of bilaterally normal animals tested
concurrently over the same period as test cats here. The frequency is
from within the most sensitive part of the cat's CAP audiogram
(Rajan et al. 1991
), and, of particular relevance here,
frequencies from this region cause TTS more easily than do other
frequencies (Rajan 1995b
), and more readily activate
previously described (Rajan 1995b
) protective effects of
crossed efferent pathways.
With monaural testing the loud tone was delivered to only the
test ear and with binaural testing simultaneously to both ears. Post-loud tone CAP thresholds were re-measured only in the test (normal-hearing) ear 5 min after the loud tone, at frequencies from 7 to 24 kHz, in a constant (but not in linear) order that was the same as
in the normative database (Rajan 1995a). The total time
taken to measure thresholds at the eight most-affected frequencies within the test range was 2.5 min.
Frequency-specific threshold desensitizations (TTSs) were
calculated as the difference between pre- and post-loud tone
thresholds. Comparisons between groups or treatments were comparisons
between TTSs at corresponding frequencies. Two-way repeated measures
ANOVAs were used to compare effects between different experimental
conditions. If the ANOVA revealed a significant difference between
conditions, or a significant interaction term between experimental
condition and frequency, unpaired Student's t-tests were
used to compare threshold losses at corresponding frequencies in the
two conditions. Comparisons of test group data were made to normative
data from normal monaurally exposed or binaurally exposed
efferent-intact groups (Rajan 1995a,b
) and normal
efferent-cut groups. For clarity, only statistically significant
P values and only comparisons of test groups to
efferent-intact groups are reported. Comparisons of test groups to
normal efferent-cut groups are discussed where relevant.
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RESULTS |
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Hearing sensitivity in cats with chronic unilateral hearing losses
Figure 1 shows examples of hearing
losses typical of the unilateral hearing-loss ear in each test
category. In animals with idiopathic hearing losses (IHL category),
this was quite varied (Fig. 1A), ranging from large losses
across most of the frequency range to small losses, just worse than the
normal range [i.e., greater than +1.64 SD from mean normal thresholds
from a large group of animals reported by Rajan et al.
(1991); significant at
= 0.05], over a small part of
the test frequency range. In CMHL animals, in which unilateral hearing
losses were created by mechanical lesions, losses were generally
stereotyped (Fig. 1B). CAP thresholds were normal until a
high-frequency at
18-20 kHz and thereafter losses increased with
increasing frequency. In one case (Fig. 1B,
) hearing
losses also extended to low frequencies, but the pattern of increasing
losses at higher frequencies was also present here. In most such
animals, at higher frequencies from
26 kHz onward, no CAP could be
evoked even at 100 dB SPL. Finally, in the Cyst-HL category, in which a
cholesteatoma-like cyst had grown into the cochlea of the hearing-loss
ear, with erosion of cochlear contents, there was total loss of
hearing, and no CAP could be evoked at any frequency even at 100 dB SPL (Fig. 1C).
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In all three test categories the nonhearing loss ear had CAP thresholds within the statistically normal range (data not illustrated). Given that some animals (in the IHL category) suffered only small losses in their hearing-loss ear, thresholds in the normal ear were checked at least three times, about 15 min apart, to re-confirm that there were no small losses in these ears.
Monaural loud tone causes lower-than-normal TTSs in the normal-hearing ear
One group from each test category was tested with monaural loud
sound exposure to the normal-hearing efferent-intact ear. This exposure
caused only small threshold shifts (TTSs) in cochlear sensitivity, with
peak threshold shift always at 15 kHz, and TTSs declining to higher and
lower frequencies (Fig. 2). In individual animals of any group (Fig. 2, A-C) there was generally
small variability in TTSs (cf. small SE bars in Fig. 2,
A-C). There was no apparent correlation between the hearing
loss in the nontest ear and the effect of the loud sound in the test,
normal-hearing ear. For example, the variability in loud sound-induced
hearing losses in the test ear in IHL animals (Fig. 2A), in
which nontest ear hearing losses could be quite varied (Fig.
1A), was similar to the variability in Cyst-HL animals (Fig.
2C), in which nontest ear hearing losses were stereotyped
(Fig. 1C). There were no significant condition effects
between pairs of test groups in the three categories (2-way repeated
measures ANOVA; for all inter-group comparisons P > 0.15 for all condition F values). There were significant
frequency effects (P always <0.001), reflecting the
frequency dependency of TTSs, but no condition × frequency
interactions as the pattern and amounts of TTSs were similar in all
three groups. Hence the three groups were pooled (i.e.,
corresponding-frequency data were pooled) for comparison to normative
(efferent-intact) data (Rajan 1995a,b
).
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The test groups suffered significantly less TTSs than normal monaurally
exposed (efferent-intact) animals (Fig. 2D), with significant effects of condition, frequency, and condition × frequency interaction (ANOVA; P < 0.001 for all 3 factors). In fact, the low TTSs in the monaurally exposed test groups
were similar to TTSs in normal binaurally exposed (efferent-intact)
animals (Fig. 2D), noting that in normal animals binaural
exposure results in crossed efferent pathway reduction of TTSs
(Rajan 1995a,b
) compared with TTSs after monaural
exposure. Comparison of pooled monaurally exposed test data to those
from normal binaurally exposed animals found no significant condition
differences. There was a significant frequency effect and a significant
condition × frequency interaction (ANOVA; P < 0.001 for both factors) because of differences at frequencies from
18-20 kHz (2-tailed Student's t-test, P always <0.001). However, at these frequencies TTSs were small (<6 dB), and
at all other frequencies there were no differences between the two
groups (t-test; P always >0.05, generally
>0.15). In general, over the frequency range with reasonably large
TTSs, there were no differences between the pooled test groups and the
normal binaurally exposed group.
Pooling data from test groups did not produce or obscure effects not already present. Comparing individual group data to normative data, TTSs in each test group (Fig. 2, A-C) were smaller than in normal monaurally exposed animals (ANOVA; P < 0.001 for all Condition, Frequency, and Interaction factors in pair-wise comparisons between the normal monaurally exposed group and each test group). When individual test groups were compared against the normal binaurally exposed group, there were no condition differences (P always >0.05 for Condition F values in pair-wise comparisons between the normal binaurally exposed group and each test group), as in the comparison of pooled test data against this normal group. However, as in the latter comparison, there were always significant frequency and interaction effects (P always <0.005 for both factors in the pair-wise comparisons), but this was due to the differences at frequencies from 18-20 kHz at which TTSs were small (<6 dB) in all groups. Thus as in the pooled data, in general, there were no differences between individual test groups and the normal binaurally exposed group.
Acute cochlear efferent activity is not responsible for lower-than-normal TTSs caused by monaural exposure in the normal-hearing ear
In normal animals (Rajan 1995a,b
) binaural exposure
with the standard loud tone results in crossed efferent-mediated
reduction of TTSs from levels caused by monaural exposure. Monaural
exposure in test animals caused low TTSs similar to the protected
levels in binaurally exposed normal animals. However, surgical
inactivation showed that acute activity in the cochlear efferent
pathways was not responsible for the lower-than-normal monaural TTSs in
test groups.
In three groups (one from each test category; Fig. 2, E-G) monaural exposure to the totally de-efferented normal-hearing ear produced low, and similar, TTSs (for all pair-wise comparisons between pairs: P > 0.05 for Condition and Interaction factors, and <0.001 for Frequency factor, reflecting the frequency dependency of TTSs). Again there was no correlation between hearing loss in the nontest ear and the effect of loud sound in the test, normal-hearing ear; e.g., the variability in loud sound-induced hearing losses in the test ear in IHL animals (Fig. 2E), with varied hearing losses in the nontest ear (e.g., Fig. 1A) was similar to that in Cyst-HL animals (Fig. 2C), with stereotyped hearing losses in the nontest ear (e.g., Fig. 1C).
For each hearing-loss category, comparison of TTSs in the monaurally exposed test group with de-efferented ears against TTSs in the corresponding monaurally exposed efferent-intact test group showed that the status of the efferent pathways had no effect. There were never any condition effects (P always >0.15 for Condition factor in inter-group comparisons between de-efferented and efferent-intact groups in each test category). There were significant frequency effects (P always <0.001 for Frequency factor in inter-group comparisons between de-efferented and efferent-intact groups in each test category), reflecting the frequency dependency of TTSs, but there were no condition × frequency interactions. Thus lesioning efferent pathways did not alter the effects of monaural exposure in the normal-hearing ear of these test groups.
As with the efferent-intact test groups, monaural exposure in de-efferented test groups caused lower-than-normal TTS. For this comparison (Fig. 2H), corresponding frequency data from the three de-efferented test groups were pooled, given the absence of differences between them. The pooled de-efferented test groups had significantly lower TTSs than normal monaurally exposed animals (ANOVA; P always <0.001 for Condition, Frequency, and Interaction factors). When the pooled test de-efferented data were compared with the low TTSs in normal binaurally exposed animals, there were no condition differences. There was a significant frequency effect and a significant condition × frequency interaction (P < 0.001 for Frequency and Interaction factors) because of differences from 12-16 kHz (2-tailed t-test, P always <0.001), where the pooled test TTSs were significantly smaller, and at 20 and 22 kHz (t-test, P < 0.05), where the pooled test TTSs were significantly larger, than in the normative database. However, at the latter frequencies TTSs were small (<2 dB); thus generally, over the most-affected frequency range, TTSs in the pooled test groups were significantly smaller than in the normal binaurally exposed animals.
In summary, the data to date show that monaural exposure in the normal-hearing ear in test groups caused significantly lower TTSs than the same monaural exposure in normal animals, but this was not due to acute activity in the cochlear efferents.
Binaural loud tone exacerbates threshold losses in the normal-hearing ear of cats with a chronic unilateral partial hearing loss but not with a unilateral total hearing loss
In three further groups (1 group of each test category), the loud tone was presented binaurally with no manipulations of efferent pathways. In IHL and CMHL groups the exposure caused large TTSs (Fig. 3, A and B), without any differences between groups (ANOVA; P > 0.05 for Condition and Interaction factors) in the frequency-dependent pattern and amounts of TTSs (P < 0.001 for Frequency factor). The TTSs were significantly greater than in monaurally exposed test counterparts of previous sections. In this comparison, for each test category (i.e., IHL or CMHL) data from monaurally exposed efferent-intact and de-efferented groups (Fig. 2) were pooled, since the presence or absence of cochlear efferents did not alter the low TTSs caused by monaural exposure in test groups. This pooled monaural-exposure data for each test category was then compared with data from the binaurally exposed efferent-intact group of the same category (Fig. 3, D and E). For IHL and CMHL categories, there were significant differences between the binaurally exposed group and pooled monaurally exposed groups (P < 0.001 for Condition, Frequency, and Interaction factors in inter-group comparisons within each test category). Thus in these two test categories in which the nontest ear had a partial hearing loss, binaural exposure produced significantly greater TTSs in the normal-hearing ear than did monaural exposure. (In each test category separate comparisons of the binaurally exposed group against monaurally exposed efferent-intact or de-efferented groups showed the same effects as when data for the monaurally exposed test groups of that category were pooled regardless of efferent status.)
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Since there were no differences between binaurally exposed IHL and CMHL
groups, they were pooled for comparison to normative efferent-intact
data (Fig. 3G). The pooled test TTSs were significantly larger than TTSs in normal binaurally exposed animals
(P < 0.001 for Condition, Frequency, and Interaction
factors) or normal monaurally exposed animals (P < 0.02 for Condition factor, <0.01 for Frequency and Interaction
factors). These differences are noteworthy: in normal animals binaural
exposure activates the crossed efferent pathway (Rajan
1992, 1995a
,b
) to reduce TTSs from that caused by monaural exposure which does not (for exposures in silence, as here)
activate any efferent effect modulating loud tone-induced TTSs. In
contrast, in the pooled IHL + CMHL data, binaural exposure did not
protect (since it caused TTSs in the test ear greater than the low TTSs
caused by monaural exposure in the same test categories), but even
exacerbated TTSs beyond those caused by monaural exposure in the normal pool.
In the Cyst-HL group, binaural exposure in efferent-intact normal-hearing ears did not exacerbate TTSs (Fig. 3C) that were similar to the small TTSs in monaurally exposed Cyst-HL groups (Fig. 3F). For the latter comparison, the two previous monaurally exposed (efferent-intact or cut) Cyst-HL groups were pooled since monaural exposure produced similar low TTSs in both groups. There were no condition differences between the binaurally exposed group and the pooled monaurally exposed data. There was a significant frequency effect (P < 0.001) but no condition × frequency interaction indicating that the frequency-dependent pattern and amounts of TTSs were similar. (Separate comparisons between the binaurally exposed group against each monaurally exposed group showed the same effects.)
Unlike the other two test categories, the TTSs in the binaurally exposed Cyst-HL group were significantly lower than in normal monaurally exposed animals (Fig. 3H; P < 0.001 for Condition, Frequency, and Interaction factors). When the Cyst-HL group was compared with normal binaurally exposed animals (Fig. 3H), there were no condition differences, but there were significant frequency and condition × frequency interaction factors (P < 0.001 for both factors) because of differences at 13 kHz (2-tailed t-test, P < 0.01), at which test group TTSs were significantly smaller, and from 18-20 kHz (t-test, P always <0.01) at which test group TTSs were significantly larger. In the latter case it must be noted that TTSs at these frequencies in both groups were small (e.g., <3 dB from 19-22 kHz, in both groups). In general, the data suggest only small, nonsystematic differences between the Cyst-HL group and normal binaurally exposed animals.
The Cyst-HL data provide a valuable control by showing that TTS exacerbation by binaural exposure in IHL and CMHL categories is not due to physical cross-over of sound from the nontest ear to the test normal-hearing ear. In the latter categories the nontest (hearing-loss) ear had only a partial hearing loss, and, in binaural exposure, there would be some outflow to the CNS from the damaged nontest ear (even if distorted compared with when both ears are normal) and the test ear. In the Cyst-HL category, growth of the cyst into the cochlea, with erosion of cochlear contents, means there is no neural outflow from that ear (see Fig. 1C); both monaural and binaural exposure produce an outflow to the CNS only from the normal-hearing test ear.
Cochlear efferents are responsible for the exacerbation of TTSs by a binaural loud tone in the normal-hearing ear of cats with a chronic unilateral partial hearing loss
Tests with one group each from IHL and CMHL categories demonstrated that cochlear efferent pathways contributed to the large threshold losses recorded after binaural exposure. In both groups binaural exposure after totally de-efferenting the normal-hearing ear caused small TTSs (Fig. 4, A and B) significantly lower than the large TTSs caused by binaural exposure in these test categories when efferent pathways were intact (also Fig. 4, A and B; P < 0.001 for all Condition, Frequency, and Interaction factors in comparisons within each test category). Thus in both test categories the large TTSs in the normal-hearing ear after binaural exposure with intact cochlear efferents included a component produced by the action of the efferents.
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As there were no condition differences or interaction effects between binaurally exposed de-efferented groups in the IHL and CMHL categories and both had similar frequency-dependent TTSs (ANOVA; P < 0.001), data from these groups were pooled for further comparisons.
The first comparison established that in the absence of the efferent component, binaural exposure produced the same low "pure" loud sound-induced TTSs as monaural exposure in these test categories. Pooled data from binaurally exposed de-efferented IHL + CMHL groups were compared (Fig. 4C) with data from monaurally exposed IHL and CMHL groups (all efferent-intact and de-efferented monaurally exposed IHL and CMHL groups were pooled since, as shown above, efferent status did not affect the TTSs to monaural exposure). There were no condition differences or interaction effects, confirming that both pooled data sets had similar frequency-dependent TTSs (P < 0.001 for Frequency factor). (Comparisons made separately of the pooled binaurally exposed de-efferented groups against pooled IHL + CMHL monaurally exposed efferent-intact or de-efferented groups found the same effects as with the overall comparison above; there was always a significant frequency term but never any condition differences or interaction effects.) Thus in IHL and CMHL categories, binaural exposure after de-efferentation produced the same small TTSs as monaural exposure (with or without intact efferents). In contrast, as shown earlier, binaural exposure with intact efferents in these test categories produced significantly larger TTSs than did monaural exposure in all test categories. These comparisons show that the exacerbation of TTSs in binaurally exposed efferent-intact IHL and CMHL test categories is due to a CAP suppression by cochlear efferents additional to the "pure TTSs" effects of the loud tone.
In normal animals, de-efferentation abolishes the protective effect
seen with binaural exposure and causes TTSs similar to the large TTSs
caused by monaural exposure with or without intact efferents
(Rajan 1995a,b
, 2000
). In contrast,
comparison here showed that binaural exposure after de-efferentation in
IHL and CMHL groups produced the same low TTSs as binaural exposure in normal intact-efferent animals, and significantly lower than TTSs after
monaural exposure in normal animals (Rajan 1995a
,b
,
2000
). Pooled data from binaurally exposed de-efferented
IHL and CMHL test groups were compared (Fig. 4D) to
normative data. TTSs in test groups were significantly lower than in
normal monaurally exposed animals (P < 0.001 for
Condition, Frequency, and Interaction factors). When the pooled test
data were compared with normal binaurally exposed animals, there were
no condition differences. There were significant frequency and
interaction effects (P < 0.001 for both Frequency and
Interaction factors), mainly because the pooled test groups suffered
significantly greater TTSs from 18-24 kHz than did the normal
binaurally exposed group (2-tailed t-test, P
always <0.05). However, at these frequencies TTSs were small (<6 dB),
and, generally, over the most-affected frequency range there were no
differences between the test groups and the normal binaurally exposed
(efferent-intact) group. As noted above, in normal animals binaural
exposure after de-efferentation produces the same large TTSs as does
monaural exposure (Rajan 1995a
,b
, 2000
).
Uncrossed efferents contribute to TTSs in the normal-hearing ear after binaural exposure in cats with a chronic unilateral partial hearing loss
Further tests in an IHL test group demonstrated that uncrossed efferent pathways were responsible for the TTS exacerbation produced by binaural exposure in this test category (and in the CMHL category). Here a midline lesion was made to cut only crossed efferent pathways to the normal-hearing ear. Binaural exposure produced large TTSs (Fig. 4E) significantly greater than the small TTSs with binaural exposure after total de-efferentation in the IHL test group of the previous section (Fig. 4F; ANOVA; P < 0.001 for Condition, Frequency, and Interaction factors). The large TTSs here were similar to those after binaural exposure with intact efferents in the IHL test category (Fig. 4F; P > 0.2 for Condition and Interaction factors), with similar frequency-dependent TTSs (P < 0.001 for Frequency factor). Thus binaural exposure with only uncrossed efferent pathways intact to the normal-hearing ear produced the same large TTSs as when all efferent pathways were intact, whereas binaural exposure after total de-efferentation resulted in significantly smaller TTSs.
It was shown earlier that, in the efferent-intact IHL group, binaural
exposure exacerbates TTSs in the normal-hearing ear to levels seen
after monaural exposure in normal animals (Fig. 3, A and
G). Since binaural exposure results in similar TTSs in crossed de-efferented and in efferent-intact IHL animals, then TTSs in
the former IHL group should be similar to TTSs in monaurally exposed
normal animals. Although comparison of these two groups found
significant differences (Fig. 4F; P = 0.012 for Condition factor, 0.001 for Frequency and Interaction factors),
this was because of larger TTSs in the IHL group at 10, 22, and 24 kHz (2-tailed t-test, P always <0.05) at
which TTSs in the normal monaurally exposed group were <0.5 dB. Thus
over the peak-affected range, when only the uncrossed pathways are
intact, TTSs in binaurally exposed IHL animals were not different from
those in normal monaurally exposed animals. It must be noted, when
looking at the individual data (Fig. 4E) for the binaurally
exposed crossed de-efferented IHL group, that this overall difference
for the group was due to data from two animals; in the other three
animals data were within the range for the normal monaurally exposed animals.
In summary, lesioning efferent pathways to the normal-hearing ear prior to binaural exposure in the IHL test group prevented binaural exposure exacerbating TTSs in the normal-hearing ear. Lesioning only the crossed pathway (leaving the uncrossed pathway intact) to the normal-hearing ear did not prevent the exacerbation of TTSs by binaural exposure.
De-efferentation of the normal-hearing ear does not alter cochlear sensitivity prior to loud sound
As noted previously, the normal-hearing ears had CAP thresholds
within the normal range. In all animals CAP thresholds were always
re-measured just prior to any brain stem surgery and immediately after
(prior to any loud sound exposure). Brain stem lesions did not ever
result in changes (not illustrated) in CAP thresholds in the
normal-hearing ears, regardless of effects on TTSs to subsequent loud
sound exposure. Thus in these test animals, there does not appear to be
any tonic efferent activity to the normal-hearing ear that modulates
CAP thresholds, as also reported in other studies in normal-hearing
barbiturate-anesthetized cats (Rajan 1995a) or guinea
pigs (Littman et al. 1991
; Rajan 1989
;
Rajan et al. 1990
). The further significance of these
data are discussed later.
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DISCUSSION |
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When there was a unilateral hearing loss in test animals, loud
sounds produced effects in the normal hearing ear that differed in four
respects from effects in animals with bilaterally normal hearing.
1) Monaural exposure caused lower-than-normal TTSs.
2) Binaural exposure did not produce any crossed efferent
pathway protection from TTSs as in normal animals for the same exposure (Rajan 1995a,b
, 1996a
). 3) In
test categories with a unilateral partial hearing loss (but not in test
animals with a unilateral total hearing loss), binaural exposure
elicited uncrossed efferent effects. In normal animals, uncrossed
efferent effects are only seen with loud sound exposure in a noise
background (Rajan 2000
) and not with exposure in silence
(Rajan 1995b
, 2000
). (In the noise
background, uncrossed efferent effects on TTSs in normal animals are
seen with a monaural loud tone exposure, and binaural exposure does not
produce larger uncrossed efferent effects on TTSs.) 4)
Finally, in normal animals, uncrossed efferents reduce TTSs (in noise
backgrounds) (Rajan 2000
), whereas in test animals with
a unilateral partial hearing loss they contributed to threshold shifts
measured after binaural exposure. Thus in test animals with a
unilateral partial hearing loss, uncrossed efferent effects on TTSs
were observed under different conditions than in normals (i.e., a noise
background was not needed, but a binaural loud sound was) and resulted
in changes opposite to those in normal animals.
In each test group tested under a particular experimental condition,
there was generally small variability in the effects of loud sound in
the normal-hearing ear despite the sometimes quite-varied pattern of
hearing losses in the nontest ear, particularly in the IHL category
(Fig. 1A). There was a tendency for CMHL animals, in which
unilateral hearing losses were generally stereotyped, to show the least
variability. Nevertheless in any one group, there was no correlation
apparent between amount of loss in the nontest ear and effects of loud
sound in the normal-hearing ear. (In reports on other studies, I will
demonstrate this is not the case if hearing losses are in a test ear
itself.) The pattern of losses caused by the loud sound in the
normal-hearing ear was the same as seen for the same exposure in
animals with bilaterally normal hearing and the variability of TTSs in
the test groups was similar to (although sometimes slightly greater
than) that seen for the effects of the same loud sound in normal
animals (Rajan 1995a,b
, 1996a
). This is
consistent with the fact that in test animals here, the test
ear had a normal audiogram. Since it is reasonable to assume that the
pattern of TTSs to a loud sound are primarily determined by cochlear
mechanics, it is then not altogether surprising, in view of normal
audiograms in the test ear, to find no changes in the
pattern of TTSs caused by loud sound in the test,
normal-hearing ear. With regard to variability of TTSs, it
appears that whatever the reason (discussed later) that unilateral
hearing loss resulted in changing the effects of loud sound and of the
efferents in the normal-hearing ear, the change was relatively
stereotyped and independent of the amount of loss in the nontest ear,
although perhaps not the frequency-extent of the loss.
In all test categories, the frequency range with hearing loss in the nontest ear overlapped to some extent, or lay directly adjacent to, the range subsequently affected by loud sound in the other (normal-hearing) ear. Where nontest ear losses were at frequencies that did not directly overlap with the frequency range affected later by loud sound in the normal-hearing ear, such nontest ear losses were in the basal cochlea. In both the Cyst-HL and CMHL categories the unilateral hearing losses were large in the basal cochlea. Similar large losses may have occurred at some stage in the nontest ear in animals in the IHL category but in some of these animals had recovered to the low levels seen at the time of experimentation. Thus the frequency range where hearing losses were present in the nontest ear may have a bearing on the effects seen in the test, normal-hearing ear.
Reduced TTSs to monaural exposure
The lower-than-normal TTSs caused by monaural loud sound to the
normal-hearing ear in all test categories were not due to acute
cochlear efferent activity: lesioning these pathways did not alter the
TTSs. In normal animals, efferent activity also does not modulate TTSs
to monaural tone-alone exposure (Rajan 1992,
1995a
) but reduces TTSs only with binaural exposure.
However, in normal animals, if one cochlea is mechanically destroyed,
monaural exposure in the other ear results in lower-than-normal TTSs
(Rajan and Johnstone 1983a
) even 1 wk after destruction
of the contralateral cochlea (Robertson and Anderson
1994
). This long-lasting change is consistent with the effect
here in which damage to one ear either had occurred (in the
mechanically lesioned, CMHL, and the Cyst-HL categories), or was
presumed to have occurred (in the idiopathic loss, IHL, category) some
time ago. One difference is that in normal animals the effect of
contralateral cochlear destruction on ipsilateral TTSs in the short
term is mediated by the crossed efferents, and lesioning this pathway
prevents the reduction in ipsilateral TTSs (Rajan and Johnstone
1989
). Acute involvement of cochlear efferents (but not
specifically the crossed efferents) in the protective effect of
long-term contralateral cochlear destruction in normal animals has also
been demonstrated where such destruction was made 8-48 h before
ipsilateral exposure (Robertson and Anderson 1994
). Thus
these effects in normal animals differ from the effects here in that
here cochlear efferents were not acutely responsible for the
lower-than-normal monaural TTS in the normal-hearing ear.
Conditioning or priming an ear with a moderate-to-loud sound can reduce
TTSs in the same ear to later loud sounds (e.g., Campo et al.
1991; Canlon et al. 1988
; Miyakita et al.
1992
; Rajan and Johnstone 1983b
; Ryan et
al. 1994
; Zheng et al. 1997a
), even many days
after conditioning. Such conditioning is unlikely to account for the
effects here. In IHL animals some prior binaural loud sound may have
overstimulated the normal-hearing ear (without damaging it, unlike the
other ear, or creating damage such that only one ear had recovered by
these experiments). However, there was no previous prolonged
stimulation in CMHL animals where a mechanical lesion created chronic
unilateral hearing losses in normal-hearing animals that recovered
without overstimulation. Nor is it likely that previous overstimulation
was involved in causing unilateral hearing loss in Cyst-HL animals.
The consistency of effects of monaural exposure in all test categories
suggests that the pertinent feature here is a unilateral hearing loss
in the nontest ear. It is also likely pertinent that the
unilateral hearing losses were chronic. In normal animals, monaural
exposure (with the same loud sound used here) of each of the two ears
in succession with some delay (90 min) does not cause different TTSs
in the second-exposed ear compared with the first-exposed ear
(Rajan 1995a
).
Finally, the present data show only that acute activity in
cochlear efferents is not needed for lower-than-normal TTSs to monaural
exposure in test animals, but does not preclude an efferent role.
Unilateral chronic hearing losses may have influenced efferent outflow
to the normal-hearing ear to produce changes that chronically reset the
susceptibility of that ear to loud sound. Acute cochlear efferent
activity, driven by the loud sound, is then not necessary to cause
lower-than-normal TTSs to that loud sound. Such re-setting of the
normal-hearing cochlea's susceptibility to loud sounds did not
manifest in a change in CAP thresholds prior to the monaural loud
sound. However, it has been proposed (Rajan 1992,
1995b
) that the protective efferent system manifests
actions only on the effects of loud damaging sound. CAP thresholds are
not measured using such sounds and any chronic efferent-induced change
in cochlear "responses" would not be detectable prior to the loud sound.
Uncrossed efferent pathways contribute to the large TTSs after binaural exposure
When the nontest ear had only a partial hearing loss (IHL and CMHL categories) but not when it had a total hearing loss (Cyst-HL), binaural loud sound exacerbated TTSs beyond those caused by monaural loud sound in all test categories. TTSs were considerably higher than those caused by binaural exposure in normal animals and similar to or higher than those caused by monaural exposure in normal animals. Since, in the first two test categories only, binaural exposure would produce some output from both ears, the exacerbation of TTSs in these two categories only appears to require input to the CNS from the nontest damaged ear as well as from the normal-hearing test ear.
The TTS exacerbation by binaural exposure in these categories was prevented by lesioning all efferent pathways but not only the crossed pathway. Thus in these test categories TTSs in the normal-hearing ear after binaural exposure were due to "pure" loud sound-induced cochlear desensitization and also uncrossed efferent effects elevating CAP thresholds. (The present results do not show whether this TTS exacerbation was due to an exacerbation of the damaging effects of the loud tone during its binaural presentation or whether a prolonged postloud tone efferent suppression of afferent activity contributed to the overall TTSs.)
It is well documented that, when activated with brain stem electrical
stimulation (Desmedt 1975; Fex 1962
;
Galambos 1956
; Gifford and Guinan 1987
;
Guinan 1988
; Rajan 1988a
;
Weiderhold 1986
), cochlear efferents can elevate CAP
thresholds, and both crossed and uncrossed medial olivocochlear system
(CMOCS and UMOCS) neurons can act so (Gifford and Guinan
1987
). Binaural tones can evoke uncrossed efferent suppression
of the CAP (Liberman 1989
), i.e., afferent neural
responses (cf., Warren and Liberman 1989a
,b
), to
nondamaging sounds. Finally, in guinea pigs with idiopathic losses in
CAP thresholds (Rajan 1989
), cochlear efferents were found to be tonically active to cause some CAP threshold elevations. Although that result was interpreted as due to the crossed pathway, at
least some brain stem lesions in that report would also have damaged
uncrossed pathways.
Nevertheless, an efferent effect contributing to post-loud sound
elevation in CAP thresholds is a novel demonstration. In normal
animals, monaural exposure with intact or cut efferents produces the
same TTSs, binaural exposure with intact efferents reduces
these TTSs through CMOCS action, and binaural exposure after
de-efferentation results in the same TTSs as monaural exposure (Rajan 1995a, 2000
; Rajan and
Johnstone 1988a
). Thus, normally, TTSs are due to damage to
cochlear processes without any exacerbation by centrifugal pathways.
Uncrossed efferent pathways consist of LOCS neurons terminating on
dendrites of cochlear afferent neurons and MOCS neurons terminating on
OHCs (Guinan et al. 1983; Warr et al.
1986
). While it is generally held (e.g., Gifford and
Guinan 1987
; Guinan 1988
; Weiderhold
1986
) that all cochlear efferent effects described to date, and
responses from single efferent neurons, are due solely to MOCS neurons
terminating on OHCs, the present results do not allow attribution of
the novel efferent contribution to postbinaural exposure threshold
desensitizations to either one of the two uncrossed pathway components.
Finally, in normal animals, binaural exposure after de-efferentation
results (Rajan 1995a,b
, 2000
) in large
TTSs identical to those produced by monaural tone exposure (with or
without efferents). In the present study when uncrossed efferent
effects were eliminated by lesioning prior to exposure in IHL and CMHL
categories, binaural exposure resulted in pure loud tone-induced
desensitizations significantly lower than TTSs produced by monaural
tone exposure in normal animals. This means (as confirmed by analyses
not reported here) that the pure loud tone-induced desensitizations in
the de-efferented binaural exposure condition here were also
significantly lower than TTSs in normal animals with the same
experimental condition (Rajan 1995a
,b
). Thus in the test
categories here, the normal-hearing ear had a reduced susceptibility to
loud tone-induced damage, and, in the absence of any efferent effect,
monaural and binaural exposure resulted in low "pure TTSs" in test
categories with a unilateral partial hearing loss. In effect, it
appears that the unilateral hearing losses resulted in changes in the
normal-hearing ear that "scaled" its susceptibility to loud sound.
Factors responsible for the absence of protective effects of the crossed efferent pathway
In normal animals the binaural exposure used here activates
CMOCS protection to reduce TTSs from those caused by the same exposure
monaurally (Rajan 1995a, 1996a
). The
absence of TTS protection by the CMOCS with binaural exposure in test
animals may be due to a change in excitability of the pathway so it is
no longer acutely activated to modulate TTSs. Changes in excitability
in single efferent neurons have been reported after acute prolonged stimulation with moderate and high-level noise stimuli (Liberman 1988
) or 5 days after a 10-day conditioning stimulus
(Brown et al. 1998
). (The latter study found no change
in drive to stimulation of the ear providing the main drive but a
slight, significant, increase in the facilitatory influence of the
other ear.) However, these aftereffects of prior long-lasting
stimulation are increases in efferent discharge rate, and it
seems unlikely that this should result in absence of
protection. Further, the studies showed effects on responses of
efferent neurons in one ear after prolonged stimulation of that ear.
Such previous overstimulation did not occur in CMHL animals, nor is it
likely to have been an issue in the unilateral hearing loss in Cyst-HL
animals. The consistency of effects between IHL and CMHL groups for
monaural and binaural exposures, and between IHL and Cyst-HL groups for
monaural exposures (reasons for differences with binaural exposure have
been suggested above), makes it unlikely that in IHL animals alone
previous acoustic overstimulation of the normal-hearing ear is
responsible for TTS effects seen here.
Alternatively, the absence of CMOCS protection with binaural
exposure may be because CMOCS end-effects no longer reduced TTSs. If
the CMOCS protects by acting only on one component of the TTSs and if
this component is not affected significantly or at all by loud sound,
then protection may not ensue. In support of this idea neither direct
electrical stimulation of cochlear efferents (Rajan
1988b; Rajan and Johnstone 1988b
) nor binaural
acoustic stimulation (Rajan 1995b
; Rajan and
Johnstone 1989
) evoke protection from TTSs to loud sounds at
levels that cause small TTSs (Rajan 1995a
,b
;
Rajan and Johnstone 1988a
) even if they strongly drive efferent neurons (Liberman 1988
; Liberman and
Brown 1986
; Robertson and Gummer 1985
). The same
manipulations do result in CMOCS-mediated protection at higher exposure
levels that produce larger TTSs, presumably because now the putative
"protected" component is affected. Consistent with this hypothesis,
in IHL and CMHL categories, TTSs after de-efferentation and binaural
exposure were similar to TTSs after monaural exposure in all test
categories. Thus as in normal animals (Rajan 1988b
,
1995b
; Rajan and Johnstone 1988b
,
1989
), when TTS is low, binaural exposure does not
result in CMOCS-mediated protection.
In summary, the absence of CMOCS-mediated protection in test animals in the binaural conditions that reveal protection in normal animals is proposed to be likely due to a re-setting of the susceptibility of one particular cochlear component/process in loud sound-induced damage in the normal-hearing ear. If this effect is specific to cochlear processes at high SPLs, then it would not result in any changes in CAP thresholds prior to the loud sound, consistent with the absence of any changes in CAP thresholds in the normal-hearing ear. The present results do not indicate what mechanisms may have been re-set in such a way.
Finally, the pure TTSs in test animals to monaural or binaural
exposure (for 11 kHz, 100 dB SPL, 10-min exposure) were similar to the
low TTSs in normal animals to a monaural 7-min exposure at the same
frequency and level (Rajan 1995a). Yet, in normal animals, the latter exposure evokes protection (Rajan
1995a
): there are lower TTSs with binaural compared with
monaural exposure. In contrast, in test animals here the "pure
TTSs" to binaural and monaural exposure were similar, suggesting that
the CMOCS may no longer protect at all in the test animals or that its
protective effect has been shifted to a higher part of its TTSs
"operating" range (Rajan 1992
,
1995b
).
Uncrossed and crossed MOCS efferents may act differently with respect to traumatic sounds
In normal animals, when protecting from TTSs to a loud tone
(in a noise background only), uncrossed efferents do not appear to act
directly on the mechanism(s) whereby loud sound causes TTSs but
prevent noise from exacerbating loud tone-induced TTSs (Rajan
2000). Thus normally, as long as the CMOCS pathway is lesioned, the "pure TTSs" caused by a monaural or binaural tone in a
background of silence are not affected by the presence or absence of
uncrossed efferents (Rajan 1995b
, 2000
).
The present data provide further support for differentiating uncrossed
efferent effects on TTSs from "pure TTSs" of loud sound. Binaural
exposure after de-efferentation (in IHL animals in which this
manipulation was tested) resulted in small TTSs similar to those after
monaural exposure in test animals. The extra TTSs with binaural
exposure in efferent-intact test animals were due to uncrossed efferent
effects additional to the pure loud tone-induced cochlear desensitization.
It may be most parsimonious, for reasons detailed in the INTRODUCTION, to assume that uncrossed efferent effects here are due to uncrossed MOCS (UMOCS) neurons, terminating on OHCs. Then, previous results in normal animals and the present results suggest that although CMOCS and UMOCS neurons exert effects on OHCs, they may do so through very different mechanisms of action or have different requirements for their activation.
With regard to activation, the only effects seen here in animals with
unilateral hearing losses after loud tone-alone exposures were due to
uncrossed pathways. In normal animals, the only effects seen after loud
tone exposures in silence were due to the CMOCS (Rajan
1995a,b
) and uncrossed pathway effects are seen with monaural loud tones only in a noise background (Rajan 2000
). This
suggests different activation requirements for CMOCS and (presumed)
UMOCS. For unknown reasons, the activation requirements for UMOCS
appear changed when there is a chronic unilateral loss: UMOCS effects are now seen when the loud tone is presented in a background of silence.
With regard to mechanisms of action, CMOCS effects during (binaural)
loud sound in normal animals protect from TTSs, whereas, as noted
above, in normal animals uncrossed efferent (presumed UMOCS) effects,
seen only to a loud sound in a noise background, prevent exacerbation
of TTSs by noise but do not directly protect from TTSs (Rajan
2000). In test animals here, uncrossed efferent (presumed
UMOCS) effects during loud sound (in a background of silence)
exacerbated post-loud sound threshold shifts, but appeared to be
additional to the "pure TTS" effects of loud sound. These differences suggest different end-effects of the CMOCS and (presumed) UMOCS with respect to actions during, or on the effects of, loud traumatic sounds. If true this represents an important distinction that
has not previously been made. Both CMOCS and UMOCS neurons are
cholinergic, and cholinergic effects on OHCs appear to be exercised
through a single nicotinic-type receptor (e.g., Nenov et al.
1996
; Puel 1995
). Current studies, either
implicitly or explicitly, assume that effects exercised by UMOCS and
CMOCS are made through the same end-mechanism on OHCs. However, such
studies have concentrated only on MOCS effects at atraumatic sound
levels, and it may be that at traumatic levels, there are distinctions of the sort speculated about here.
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ACKNOWLEDGMENTS |
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This work was supported by National Health and Medical Research Council of Australia Grant 970505.
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FOOTNOTES |
---|
Author E-mail: ramesh.rajan{at}med.monash.edu.au
Received 14 August 2000; accepted in final form 20 November 2000.
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REFERENCES |
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