The effect of contralateral stimulation on cochlear resonance and damping in the mustached bat: the role of the medial efferent system

HBIRIIIG RESFAKH

ELSEVIER

Hearing Research 86/1,2 (1995) 111-124

The effect of contralateral stimulation on cochlear resonance and damping in the mustached bat: the role of the medial efferent system O.W. Henson, Jr. a,*, D.H. Xie a, A.W. Keating a, M.M. Henson b a Department of Cell Biology and Anatomy, 108 Taylor Hall, CB #7090, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA b Department of Surgery, Division of Otolaryngology / Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

Received 6 June 1994;revised 14 February 1995; accepted 3 March 1995

Abstract

In the unanesthetized mustached bat, stimulation of the ear with an acoustic transient produces damped oscillations which are evident in the cochlear microphonic potential. In this report we demonstrate how the decay time of these oscillations is affected by broadband noise presented to the contralateral ear (CLN). In the absence of CLN, the mean decay time was 1.94 + 0.23 ms, but during the presentation of CLN the decay time consistently decreased. The changes were finely graded, the higher the CLN, the greater the change. The effect could be maintained at a constant level for extended periods of time and this was evident when the CLN exceeded 40 dB SPL. The latency of the reflex for 64 dB noise was about 11 ms and near maximum changes occurred within 15 ms of CLN onset. Sectioning medial efferent nerve fibers in the floor of the fourth ventricle or the administration of a single dose of gentamicin eliminated changes produced by CLN. The prominence of CM responses to damped oscillations and the robust changes in response to CLN make the mustached bat an excellent model for studying the influence of the medial efferent system on cochlear mechanics. Keywords: Cochlear microphonic; Resonance; Efferent; Olivocochlear; Mustached bat

I. I n t r o d u c t i o n

It is well known that stimulation of one ear with broadband noise significantly affects the response properties of the contralateral ear. This has been shown in studies of cochlear microphonic and neural potentials, otoacoustic emissions, and distortion products (see for example Buno, 1978; Mott et al., 1989; Warren and Liberman, 1989a,b; Brown and Norton, 1990; Puel and Rebillard, 1990; Veuillet et al., 1991; Hildesheimer et al., 1990; Collet et al., 1990a, Collet et al., 1990b; Collet et al., 1992; ChEry-Croze et al., 1993; Kujawa et al., 1993). Studies have also shown that sectioning or blocking the efferent nerve fibers to the outer hair cells (OHCs), or tumors that affect the fibers, eliminate the suppres-

* Corresponding author. Fax: +1 (919) 966-1856. e-mail: [email protected]. 0378-5955/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDI 0378-5955(95)00061-5

sive effect of contralateral noise (CLN) (Siegel and Kim, 1982; Maurer et al., 1992; Williams et al., 1993; Kirk and Johnstone, 1993). This is especially evident from studies involving reversible blocking of the medial efferents which innervate the OHCs (Kujawa et al., 1993; Smith et al., 1994). On the basis of these and other studies it is now clear that efferent nerve fibers cause the OHCs to change their length and modulate the mechanical properties of the inner ear (see Zenner, 1993). Evidence suggests that the net effect of O H C efferent excitation is a damping of the oscillatory motion normally produced by sound waves. Although changes in damping have been implied by suppression of neural potentials, otoacoustic emissions and distortion products there have been no measurements of the actual changes in damping. The ear of the mustached bat seems well-suited for such measurements. Electrodes can be chronically implanted near the cochlear aqueduct and cochlear microphonic (CM) potentials can be

O. 14d Henson, Jr. et al. / Hearing Research 8 6 / 1 , 2 (1995) 111-124

112

recorded for a period of months in animals fully recovered from the effects of anesthesia and surgery (Henson and Pollak, 1972). In the mustached bat transients associated with the offset of electronically generated tones near 61 kHz cause the ear to ring for relatively long periods and the damping characteristics of the cochlear partition can be studied by measuring the decay time of the CM potential produced by the damped oscillations. The purpose of this report is to illustrate the changes in damping that occur during the presentation of CLN and to show that these changes are the result of activity of the medial efferent nerve fibers. Preliminary reports dealing with this subject have been published in abstract form (Henson et al., 1993, Henson et al., 1994).

2. Methods

2.1. Animals used The animals used in this study were mustached bats,

Pteronotus parnellii parnellii from Jamaica, West Indies. Permission to collect the animals for research was approved by Natural Resources Conservation Authority and Ministry of Agriculture, Division of Veterinary Services of Jamaica. The results are based primarily on six chronic preparations; their care and use was approved by the Institutional Animal Care and Use Committee at The University of North Carolina at Chapel Hill, Animal Assurance N u m b e r A3410-01.

2.2. Implantation of chronic electrodes In all cases a recording electrode was placed near the cochlear aqueduct of the left ear to record CM potentials. The preparation, surgery and electrode implantations were carried out in sterile facilities in the Division of Laboratory and Animal Medicine at the University of North Carolina; the method of implantation has been described in previous publications from our laboratory (Henson and Pollak, 1972; H u f f m a n and Henson, 1993a,b). The technique involves surgical exposure and cleaning of the posterior, dorsal part of the skull, drilling a small hole near the edge of the lambdoid ridge and the stereotactic placement of a sharpened, epoxy insulated, tungsten electrode near the intracranial opening of the cochlear aqueduct. A ground electrode was implanted in the region of the occipital cortex. The electrodes were glued in place with cyanoacrylic glue when the amplitude of CM potentials elicited by key jingles was high. After electrode implantation, the animals were wrapped in a cloth and placed in a recovery area. Experiments were carried out on animals that appeared to be fully recovered from the effects of anes-

thesia and surgery as judged by vigorous flight and their ability to echolocate and avoid obstacles. Experiments were begun several days after surgery and were continued at regular intervals for a period of several months.

2.3. Electrophysiology All experiments were carried out in a recording chamber lined with acoustic foam. The body temperature of the animals was monitored at regular intervals and was typically in the normal 39-41 ° C range. Monitoring the body t e m p e r a t u r e was important because small changes are known to change the resonance frequency and response properties of the mustached bat's ear (Huffman and Henson, 1993a,b). During recording sessions the animal's body was placed in a lined, styrofoam sandwich that was suspended from a rod with a rubber band. The animal's head was stabilized by a clamp that attached to the connector pin of the ground electrode in the skull. With this arrangement, the head was fixed relative to the loudspeakers but the body was free to move. The animals appeared comfortable and no tranquilizers or drugs were used for sedation. Recording periods typically lasted two hours.

2.4. Acoustic stimulation Acoustic stimuli were produced by 1.5-inch electrostatic transducers (Polaroid Corp.). One free field loudspeaker was positioned about 45 degrees to the left of midline and 13 cm from the ear; its position was adjusted until the maximum CM was obtained for a low level stimulus near 61 kHz. An accurate (50 ppM) 12 MHz synthesized function generator (Wavetec Model 23) was used to generate the tone pulses. The physical characteristics of the pulses (frequency, duration, rise-decay time, SPL, interstimulus intervals) were computer controlled with custom designed hardware and software. For decay time measurements, the signal delivered to the implanted ear was set at or near the resonance frequency of the ear, as determined by F F T analysis of the CM (see Henson et al., 1990a; Huffman and Henson, 1993a,b). Tone pip duration was 2 ms and the SPL was 60-65 dB, 5 - 1 0 dB lower than the reflex threshold of the middle ear muscles. Tone pips were delivered at a rate of 10 Hz. The rise and decay times were set at 0.1 ms so that a strong acoustic transient was present at the start of the decay time. This transient caused the cochlear partition to undergo free, d a m p e d oscillations (see Fig. 1). The second Polaroid transducer was mounted in a small metal box with a round opening for the speaker plate; the rim of this opening was sealed to the 46 m m diameter mouth of a small plastic funnel. The other

O. W. Henson, Jr. et aL / Hearing Research 8 6 / 1 , 2 (1995) 111-124

A

Transient CM to s t i m u l u |

Stimulus

CM to ringing

(damped oscillations)

/

2 msec

;lent

B /

/I

CM envelope

~ t . Supefimlx~ed computer '~ / estim,e of decay

iouvl

Dee~ I ~ time ~ ~

I

I msec Ringing time

[

Fig. 1. Characteristics of the CM potential evoked by the standard stimulus used to stimulate the ear of the mustached bat. In A, the lower trace shows the 2.0 ms pure tone pulse that matched the resonance frequency of the bat's ear (in this case 61.2 kHz). Note the decay of the CM amplitude following the acoustic transient (indicated by vertical line) at the onset of the 0.1 ms signal decay. The CM during the decay is produced by ringing (damped oscillations) of the cochlear partition and the frequency of the ringing is the resonance frequency of the bat's ear. B shows the envelope of CM in more detail and illustrates both the ringing time and a computer estimate of decay time within a selected part of the envelope (dark line); based on a 500 kHz sampling rate. Decay time was calculated as the time required for the selected segment of the decaying CM to fall to 36% of its starting amplitude.

end of the funnel was positioned near, but not touching, the external acoustic meatus. This was used to deliver continuous broadband noise over a selected period of time. Spectral analysis of the noise at the opening of the funnel showed a broad p e a k output centered near 40 kHz; the signal was down 6 dB at 25 kHz and 62 kHz. The onset of the CLN and the tone pip could be independently controlled. The noise was generated by custom designed electronics. The SPL of the noise was adjusted in 3 dB steps by a custom made attenuator. Sound pressure levels were measured with a Briiel and Kjaer microphone (model 4135) which was calibrated with a Briiel and Kjaer pistophone (model 4220). The SPL of the CLN was usually set below the reflex threshold of the middle ear muscles (MEMs), ca 70 dB. The threshold of the reflex and the amount of attenuation produced by M E M contractions was determined by attenuations of the CM potential in the

113

implanted ear as a function of the CLN level (see Fig. 4A). With the ultrasonic frequencies used and the barrier effect of the contralateral pinna, there was no evidence of significant crosstalk between the two ears. When the CLN was 74 dB or less we saw no CM in the implanted ear in response to the noise. All effects attributed to CLN were eliminated when the contralateral pinna was folded over the external acoustic meatus to block the sound path (see Fig. 5A). CM potentials were amplified (10,000 × ) and filtered (10 k H z - 1 0 0 kHz) with a commercial preamplifier ( E G and G, Model 113). CM potentials were additionally filtered with a custom, computer controlled bandpass filter (Q = 4) which greatly improved the signal-noise ratio. The decay time of the ringing was measured with custom analysis software on an I B M A T computer. CM potentials were first sampled at a high rate (500 kHz) by the computer. These samples were then rectified and processed to obtain the envelope of the CM. Samples of the envelope were processed further to obtain an estimate of the decay time of the transient-induced resonance. This was done by linearizing the samples (multiplying by the natural log) and then performing linear regression analysis to determine the slope of the line that best fit the linearized samples. In this way, decay time was estimated as the reciprocal of the slope of the regression. A plot was obtained which closely matched the exponential decay of the CM (Fig. 1B). To show that the efferent nerve fibers to O H C s were responsible for changes in the decay time and resonance, the fibers were sectioned in the floor of the fourth ventricle. Transection was accomplished with a fine, etched, tungsten electrode, the tip of which was stereotactically placed in the floor of the fourth ventricle near the point where the crossed and uncrossed fibers course near the midline. The electrode was inserted through a small, midline hole in the dorsal surface of the skull; the diameter of the hole was just sufficient for passage of the electrode. With the electrode fixed to the drive unit, the animal's head was moved forward and backward. The movements were controlled with a micromanipulator and they extended over a distance of about 1.0 m m in each direction. The tip of the electrode produced a rostral-caudal, arcshaped lesion. The amount of movement of the electrode was greatest at the tip and minimal within the overlying cerebellum. The effect of contralateral noise on the cochlear potentials was tested over a period of several days after the lesion. Analysis of the success of the efferent fiber lesions was accomplished by reconstructing the arc-shaped lesion in serial sections of the brain stem. In this way the depth of the lesion and its proximity to known position of the fibers was established. In addition, surface preparations of the cochlea

114

O.W. Henson, Jr. et al. /Hearing Research 8 6 / 1 , 2 (1995) 111-124

were stained for A C h E according to the method outlined by Xie et al. (1993). The effectiveness of a lesion was assessed by determining the proportion of O H C s without efferent terminals 2 - 3 weeks after the lesion was made. In the mustached bat, each O H C normally has a single large efferent terminal (Bishop and Henson, 1988) and with successful lesions the majority (70% or more) of the terminals were missing.

SPL -

/

P

-

-

~

90 DB

-- - - 86

3. Results -~'--

~

--

7O

3.1. The shape of the CM enuelope Each tone pip matched to the resonance frequency of the cochlea evoked a CM response that had a slow rise time c o m p a r e d to the stimulus and following the transient at the onset of the signal decay, there was a ringing which produced a CM potential with an exponential decay (Fig. 1). We will disregard that part of the CM prior to the transient and concentrate on the ringing-evoked CM.

- ~ ' ~ " ~ ' ~

3.3. The decay time of the CM enuelope

,, ^ . . . .

58

46

@- i i

3.2. Ringing time As shown in Fig. 2, the ringing time is SPL and CM amplitude dependent. In general, the higher the SPL of the tone pip and larger the CM amplitude, the longer the ringing time. In our preparations the CM envelope showed a progressive decay when the tone pip SPL was kept at or below 60-70 dB. With sound pressure levels near 65 dB the ringing time was typically in the 4 - 6 ms range. At higher SPLs the ringing time was usually longer but was variable and aberrations in the envelope were often noted; in some cases the ringing was maintained at a constant amplitude before any decay began or it was greatly prolonged. In this study, SPLs that caused such aberrations were avoided. Because ringing time in the awake preparation was variable and so dependent on CM amplitude, it was of little or no value for assessing changes in the mechanical properties of the ear.

"

0

1.4 2.8 4.2 5.6 70 8.4 9.8 11.2 TIME, MSEC AFTER TRANSIENT (T)

Fig. 2. CM envelopes as a function of sound pressure levels. Note the dependence of the ringing time on the stimulus SPL. The position of the transient (T) that caused the subsequent ringing is indicated by a vertical line. The zero point on the time axis is aligned to this transient.

were alert animals that moved their pinnae at will and contracted their middle ear muscles. Experiments were performed to show that changes in the stimulus levels reaching the ear were not influencing the results. Fig. 3 illustrates the independent nature of the ringing-evoked CM amplitude (the highest amplitude of the CM following the acoustic transient) and the

3.5

40 0

°t

79 ~B

2.5

Decay time is the time required for the ringingevoked CM amplitude to decrease from a selected starting amplitude to a point 0.3678 (36%) of the value at the start point (see Fig. 1B). Decay time in a system with d a m p e d oscillations is not dependent on the energy in the resonance-evoking stimulus but on the amount of energy lost with each cycle. This depends on the mechanical properties of the vibrating structure(s). In other words, neither the SPL of the stimulus nor the amplitude of the CM should affect decay time. This is an important consideration because our preparations

0

(13

OJ

30

1.5

67 ,

~ 0.5

61

o4

pecay

20 ~

Time

.........*........ CM

100

Tone pip level, dB SPL Fig. 3. Data showing the independence of decay time on tone pip SPL and CM amplitude. Each data point represents a single measurement collected about every 4.3 s. After seven signal presentations at a given level, the tone pip SPL was increased 3 dB.

O. IV.. Henson, Jr. et aL / Hearing Research 8 6 / 1 , 2 (1995) 111-124

decay time. In these experiments m e a s u r e m e n t s were made approximately every 15 s and at regular intervals the tone pip SPL was increased in 3 dB steps. It can be seen that the decay time was relatively constant while the CM amplitude progressively increased as the SPL of the tone pip was changed over a range of 18 dB. In six preparations where many m e a s u r e m e n t s were made, the mean decay time in the absence of a contralateral stimulus was 1.94 _+ 0.23 ms (see Table 1).

A

115

12o ;> ::1 100

~" <

80

3.4. Middle ear muscle contractions

60 50

Middle ear muscle ( M E M ) contractions were sometimes observed during experiments and these were evident from changes in the CM amplitude and ringing time. In order to show that decay time m e a s u r e m e n t s were independent of M E M activity the decay time was studied while M E M contractions were absent or sustained by stimulating the contralateral ear with a pulsed (10 ms on, 10 ms off), 20 kHz tone of variable strength. As shown in Fig. 4A, the amplitude of the CM was constant when the contralateral tone was less than 70 dB. Above this reflex threshold level, M E M contractions attenuated the CM by progressively greater amounts but regardless of the amount of attenuation, the decay time remained constant (Fig. 4B).

I

I

I

I

I

go

70

80

90

100

110

C O N T R A L A T E R A L P U R E T O N E , dB SPL

B

3.0 r,,.3

2.5 2.0

~

1.5

< ~

1.0 0.5 50

I

I

!

!

I

60

70

80

90

100

110

C O N T R A L A T E R A L P U R E T O N E , dB SPL

3.5. The reflexive changes produced by contralateral noise While contralateral 20 kHz stimuli had no effect on decay times broadband contralateral noise produced a characteristic change in the slope of the decaying CM envelope and in decay time values. As shown in Fig. 5A, the slope of the decay was steeper in the presence of C L N than under control conditions (no CLN or when the contralateral pinna was folded over the external acoustic meatus during C L N presentation). Thus, the observed effects were entirely the result of a contralateral acoustic reflex. In Fig. 5, the superimposed traces with and without CLN show a slight change in CM amplitude during the presence of CLN. In our preparations we never saw an increase in CM amplitude during CLN; it either remained constant or decreased. Decreases in CM amplitude can be explained by resonance frequency shifts (see below).

Fig. 4. Data showing that middle ear muscle (MEM) contractions do not affect decay times of damped oscillations. A shows the maximum CM amplitude to the standard test stimulus (62 kHz, 2 ms, 70 dB) presented to the implanted ear as a function of the SPL of a 20 kHz pulsed tone (10 ms on, 10 ms off) in the contralateral ear. Note that the CM amplitude begins to diminish when the SPL of the 20 kHz tone exceeds about 70 dB, the MEM reflex threshold. With higher SPLs the CM amplitude was progressively more attenuated. Each data point is the average value for 32 stimuli. B shows decay time values determined for the same animal with the SPL values of the contralateral, pulse pure tone in the same SPL range shown in A. For each data point the standard deviations are based on 9 measurements. The decay time values are relatively constant regardless of whether the measurements were made in the absence of MEM contractions or during strong contractions.

The effect of C L N on decay time was finely graded. Stimuli as low as 40 dB were effective in producing noticeable changes and the louder the CLN the greater the effect (Figs. 5B and 6). It was not possible to obtain

Table 1 Batch No.

Without CLN

With CLN

Q (mean ± SD)

DT (mean + SD)

SPL, dB

Q (mean ± SD)

DT (mean ± SD)

% Change

PPP030394 PPP090193 PPP101393

420 + 21 395 + 32 468 ± 57

2.19 ± 0.11 2.00 + 0.16 2.40 ± 0.29

PPP031094 PPP011894a PPP011894b Mean

353 319 314 378

1.83 1.61 1.63 1.94

67 67 67 Mean 61 61 61 Mean

159 206 293 219 131 216 166 171

0.82 1.00 1.51 1.11 0.67 1.00 0.86 0.84

37.4 50.0 62.9 51.25 36.6 62.1 52.7 52.55

± ± ± +

29 90 42 45

+ ± ± ±

0.15 0.46 0.22 0.23

± ± ± ± ± ± ± ±

20 27 67 74 39 19 37 31

DT, decay time;. CLN, contralateral noise;, n = 14 for each mean; Tone pip SPL = 64 dB.

+ + ± ± ± + ± ±

0.10 0.14 0.34 0.38 0.20 0.09 0.19 0.16

O.W. Henson, Jr. et al. /Hearing Research 8 6 / 1 , 2 (1995) 111-124

116

d a t a on t h e m a x i m u m s u p p r e s s i v e effect of C L N b e c a u s e l o u d stimuli c a u s e d t h e M E M s to c o n t r a c t so strongly t h a t C M a m p l i t u d e s w e r e o f t e n r e d u c e d to such low levels t h a t d e c a y t i m e m e a s u r e m e n t s c o u l d n o t b e m a d e . A l s o , with l o u d C L N t h e i m p l a n t e d e a r was a d d i t i o n a l l y s t i m u l a t e d by t h e c o n t r a l a t e r a l noise and continuous resonance occurred. W i t h C L N in the 6 1 - 6 7 dB r a n g e t h e r e was typically a b o u t a 5 0 % r e d u c t i o n in t o t a l d e c a y t i m e ( T a b l e 1). This t a b l e also shows c h a n g e s in quality factor ( Q ) a s s o c i a t e d with C L N . Q is a s t a n d a r d m e a s u r e o f d a m p i n g . T h e h i g h e r the Q t h e m o r e lightly d a m p e d a n d s h a r p l y t u n e d a system is. It can b e e x p r e s s e d several ways: Q = 2 z r ( e n e r g y s t o r e d / e n e r g y loss p e r cycle)

A. CLN 40 dB 2. 1 CLN OFF

CLN ON

I

0.71 0

.

, 100

-

, 200

•

300

B. CLN 46 dB 2. 1

CLN ON

I

z~

0.71

-

0

or

,

CLN OFF

•

100

,

. 300

200

C. CLN 52 dB

Q = Decay time x w x Cochlear resonance frequency

<

2.1

I

CLNON

CLNOFF

•

.

!

A

~" O

T [-

L

PPP041792 F

CLN' 55 dB. pinna

0.71 0

nor'real.

, 100

, 200

300

D. CLN 58 dB 2. 1

"~'*~ U

o

A1so curve with no noise

J

rPl

• 0

2

4

6

8

;4 1'6

I0

Time, msec

B =-

, 100

•

, 200

• 300

TIME, SEC. Fig. 6. Changes in decay time as a function of the CLN level. These graphs illustrate the sustained nature of the suppression of damped oscillations caused by CLN.

PPP041792

C L N 52 dB

..

CLN OFF

1, -L%~.'~

0.7/

0

CLN ON

C L N 49 dB

~

normal

~"

C L N 40 dB

0

J

stimulus .

i

2

4

6

8

Time,

10

12

14

1'6

msec

Fig. 5. The effect of contralateral noise on CM potentials produced by d a m p e d oscillations (ringing) of the cochlear partition following

an acoustic transient (T). In A, note that the slope of the decay during the presentation of 55 dB CLN is much steeper than when no CLN was present, or when the pinna was folded over the contralateral external acoustic meatus during the presentation of noise. B illustrates the graded nature of changes in ringing time as a function of the noise level. Note that a change in ringing time is evident even when the CLN was 40 dB. Each envelope trace represents the average response to 32 stimuli.

Q v a l u e s will g e n e r a l l y n o t b e cited in this r e p o r t b e c a u s e g r a p h s of c h a n g e s in d e c a y t i m e a n d Q have the same shape and the percentage changes of decay t i m e a n d Q a r e essentially t h e same. Q values are, however, i n c l u d e d in T a b l e 1 since they r e p r e s e n t a s t a n d a r d way o f expressing d a m p i n g in m e c h a n i c a l systems. T h e s u s t a i n e d a n d g r a d e d n a t u r e of the c h a n g e s b r o u g h t a b o u t by C L N is well i l l u s t r a t e d in Fig. 6. H e r e t h e d e c a y t i m e e s t i m a t e s for e a c h s a m p l e a r e p l o t t e d as a function o f time b e f o r e , d u r i n g a n d after C L N p r e sentation. T h e d a t a shown in Fig. 6 a r e r e p r e s e n t a t i v e o f t h o s e o b t a i n e d for all of o u r p r e p a r a t i o n s in t e r m s of t h e s t e a d y state a n d a m o u n t of s u p p r e s s i o n with C L N o f low to m o d e r a t e levels. In s o m e cases, however, c h a n g e s in d e c a y t i m e d u r i n g t h e b e g i n n i n g o f t h e C L N p e r i o d w e r e g r e a t e r t h a n t h e s u s t a i n e d values ( p a n e l B, in Fig. 6).

O.W.. Henson, Jr. et al. /Hearing Research 86 /1,2 (1995) 111-124

117

3.6. The time course of the CLN-evoked reflex A. CLN 55 dB

By regulating the time of tone pip stimulation relative to the onset and offset of the contralateral noise, we were able to examine the latency of the CLN-evoked reflex, the time course to attain a maximum decrease in decay time and the time required to return to p r e - C L N levels (Fig. 7). In three animals where measurements were made with the CLN between 60 and 76 dB, the latency was typically in the 10-12 ms range. With fainter stimuli the latency a p p e a r e d to be longer, but the change in latency with SPL was not studied in detail. Marked reductions in decay time were seen within 15 ms of the beginning of the noise (i.e. 4 ms after the latency) and maximum or near maximum effects were evident within 15-25 ms. After the end of the CLN, the decay time recovered to near normal values in about 15 ms.

61700 CLNON 61600

61500

PPP031094

~ t~

~

61400 100

B. CLN6I dB 61700

CLNON 61600

CLNOFF

61500

61400

i

100

3. 7. Resonance frequency changes as a consequence of CLN When the resonance (ringing) frequency was plotted as a function of tone pip SPL, there was always a

61700 t

CL~c:N ~ CLNOFF

61400|

2.5

200

C. CLN 67 dB

:°:1

A

200

i

100

200

PPP030394 TIME, SEC. Fig. 8. The effect of CLN on the cochlear resonance frequency (CRF). Note that the greatest change tends to occur with the first several stimuli and that the amount of change is not sustained nor dependent on the SPL of the CLN. The test tone SPL was 67 dB.

1.5 O O E

1.0

= 10

d

i 2O

= 3O

= 40

60

Time, from start of CLN

B O O

2.5

121 2.0

1.5

PPP030394 1.0 0

i

i

10

20

= 30

i 40

50

Time, from end of CLN Fig. 7. The time course of changes in decay time produced by CLN with an SPL of 76 dB. The top graph (A) shows that significant changes do not begin to occur until about 11 ms after the beginning of the noise. Note the near maximum reduction in decay time at 15 ms. The lower graph (B) shows the recovery of decay time after the end of the CLN. Each point on the graph shows the mean and SD for 10 samples. See Methods for parameters of standard stimulus used.

decrease in frequency with an increase in SPL (ca 10 H z / d B ) , but the amount of change was variable. In the presence of C L N the resonance frequency always increased but, unlike decay time, the amount of change was not as dependent on the SPL of the noise (Fig. 8). Maximum shifts of about 125 Hz were recorded. A clear correlation between the magnitude of resonance frequency changes and changes in decay time could not be established. This, and the general variability of the frequency change may be explained by the dependence of the resonance frequency on CM amplitude but the independence of decay time on this factor. The maxim u m amount of resonance frequency shift during the presentation of CLN was often seen with the first few stimuli of a series (Fig. 8).

3.8. The effect of COCB transections Lesions placed in the floor of the fourth ventricle were designed to transect the COCB. This bundle

O.W. Henson, Jr. et al. /Hearing Research 86 / 1,2 (1995) 111-124

118

normally transmits about 70% of the MOC fibers projecting to the contralateral ear (Bishop and Henson, 1987). As previously mentioned, successful lesions placed in the vicinity of this bundle resulted in degeneration of 70% or more of the nerve terminals on OHCs. It is probable that fibers from both the ipsilateral and contralateral efferent nuclei (DMPO) were damaged since many ipsilateral fibers course close to the midline. In most cases lesions eliminated or greatly reduced the effect of CLN on changes in decay time (Fig. 9). In cases where the attempted lesion missed the COCB, there was no change in the effect of CLN. Although changes in decay time with CLN were eliminated or reduced by midline lesions, changes in resonance frequency were variably affected. Sometimes the resonance frequency shifts were almost totally abolished and at other times the effect was slightly reduced. Again, this may be explained by the CM amplitude dependent nature of the resonance frequency.

A

Before gentamicin 3.0

2.5

CLN ON

OFF

*,,v,4,,

~5 r,/3

1.0

PPP070894

0.5

>. < t3

B

,

,

,

50

100

150

200

5 Hours after gentamicin

3.0

t

2.5

CLN ON

OFF

a.o 0.5

l/

-PPP070894 •

,

50

-

,

•

100

,

150

-

200

TIME, SEC. Fig. 10. The effect of CLN before and after administration of a single dose of gentamicin.

3.9. The effect of gentamicin administration Recent studies by Smith et al. (1994) have shown that a single dose of gentamicin (an aminoglycoside antibiotic) will block the action of the cholinergic olivocochlear efferent nerves in the guinea pig. This drug was administered in four bats (90-120 m g / k g body wt.) and it completely eliminated the suppressive effect of contralateral noise on decay time. The effects of gen-

A. BEFORE COCB CUT

tamicin were usually more striking than those obtained with COCB transection (Fig. 10) in the sense that there was no suggestion of suppression during CLN; in the COCB lesioned animals the data points sometimes showed a wider, more variable range during CLN (compare Figs. 9B and 10B). The disruptions of the efferent reflex by gentamicin was temporary and full recovery occurred within 24-48 h. A more complete report on the effect of gentamicin on CM and neural potentials in the mustached bat is in preparation.

4

CLN off

CLN on

4. Discussion

1

03

E

01 090293.... /

0

50

100

150

200

250

.e >., t~

a

B. AFTER COCB CUT 4CLN on

3.°) 2"

CLN o f f

D

D ~

[] IB

m

m

ta m

'~ ~

~

~=EI

K!

0

IBM

lIB

--El

1"

PPP 0 9 0 2 9 3 o 50

i l O0

Time,

•

i 150

•

i 200

•

250

sec

Fig. 9. Comparison of effects of CLN on decay time before (A) and after (B) transection of the COCB. See Methods for parameters of standard stimulus used.

In this study we used an animal with one of the most sharply tuned auditory systems known to Nature. Much of the fine tuning appears to be dependent on the remarkable resonance properties of the cochlea and on associated specializations of basic structures common to the ears of all mammals, i.e. the basilar membrane, tectorial membrane, spiral ligament, fluid filled spaces and OHCs (Henson, 1978; Henson and Henson, 1988,1991; K6ssl and Vater, 1990; Vater, 1988). In other mammals resonance is also considered an important feature of the cochlea and one that is essential to sharp tuning. Although lightly damped oscillations indicative of a highly resonant system are not as pronounced in other mammals as they are in the mustached bat, they do occur (M¢ller, 1970 ; Rhode, 1974; LePage and Johnstone, 1980; Ruggero and Rich, 1991; Ruggero et al., 1992). Resonance along the mammalian cochlear partition was predicted by von Helmholtz in 1863 (c.f. Zwislocki, 1984); it has been demonstrated by

O.W. Henson, Jr. et al. /Hearing Research 8 6 / 1 , 2 (1995) 111-124

a number of techniques (Rhode, 1974; LePage and Johnstone, 1980; Ruggero and Rich, 1991; Ruggero et al., 1992) and it is now considered an essential component of most theories of hearing and sharp tuning (see de Boer, 1979,1990; Dancer, 1992; Davis, 1983; LePage, 1990; Dallos, 1992; Dallos et al., 1990,1991; Neely, 1993; Neely and Kim, 1983; K6ssl and Vater, 1985; Zwislocki, 1980,1983,1984,1986; Karlsson et al., 1991; Mountain and Hubbard, 1994). Thus, our findings concerning resonance and damped oscillations not only have implications in terms of auditory processes in mustached bats but also in terms of basic auditory mechanisms in other mammals as well. It is clear that the mustached bat provides an excellent model for studies of MOC efferent system. We have previously shown that the MOC system is represented throughout the cochlea (Bishop and Henson, 1988) and the present study demonstrates that a robust reflex with sustained effects occurs in response to CLN. Also important is the finding that the MOC system in the bat can be reversibly eliminated with a single injection of gentamicin. The present study shows that CLN produces a reflex that reduces the decay time of transient-evoked damped oscillations of the cochlear partition. We demonstrated that with moderate SPLs the changes in damping are produced by a reflex with a latency of about 11 ms and that a substantial reduction in decay time and Q, i.e. an increase in damping, can be achieved in less than 5 ms after this latency. The changes are finely graded in accordance with the SPL of the CLN. The lesion studies show that medial efferent fibers are an essential component of the reflex. It is known that these cholinergic fibers are distributed to the OHCs of the mustached bat (Bishop and Henson, 1988; Wilson et al., 1991; Xie et al., 1993) and other mammals (see Warr, 1992) and that the OHCs are contractile elements (see Zenner, 1993 for review) which change their size and shape when acetylcholine and other neurotransmitters are applied to them (Brownell et al., 1985; Housley and Ashmore, 1991; Plinkert et al., 1991; Slepecky et al., 1988; Sziklai and Dallos, 1993) or with COCB stimulation (Patuzzi and Rajan, 1990). There is clearly a feedback system which modulates the mechanical properties of the inner ear. As far as we are aware, the present study is the first to examine changes in the damping characteristics of the cochlear partition, although there have been numerous observations of suppression of cochlear emissions (Mott et al., 1989; Collet et al., 1990a;b,1992; Puel and Rebillard, 1990; Maurer et al., 1992; Plinkert and Lenarz, 1992; Harrison and Burns, 1993; Berlin et al., 1993; MorantVentura et al., 1993; Williams et al., 1993; Kujawa et al., 1993; Kashiwamura et al., 1993; Kirk and Johnstone, 1993; Ch6ry-Croze et aI., 1993; Norman and Thornton, 1993; Rossi et al., 1993) and distortion prod-

119

uct amplitudes (Mountain, 1980; Siegel and Kim, 1982; Brown and Norton, 1990; Kirk and Johnstone, 1993) and receptor potentials, single-multi unit responses and compound action potentials (Fex, 1962; Wiederhold, 1970,1986; Wiederhold and Kiang, 1970; Buno, 1978; Brown and Nuttall, 1984; Guinan, 1986; Gifford and Guinan, 1987; Winslow and Sachs, 1987; Rajan and Johnstone, 1988; Liberman, 1989; Warren and Liberman, 1989a,b; Smith et al., 1994) which can in part be explained by changes in damping (Siegel and Kim, 1982). Many theories have been advanced concerning the function of the medial efferent system. Most revolve around the fact that changes in efferent activity modulate cochlear mechanics and these in turn regulate the sensitivity and tuning of the system. Some of the major interrelated functions that have been assigned to the medial efferents include: (1) protection against acoustic overstimulation and reduction in associated threshold shifts (Cody and Johnstone, 1982; Puel et al., 1988; Rajan and Johnstone, 1983,1988; Rajan, 1988a,b; Rajan et al., 1990; Liberman, 1989,1991; Warren and Liberman, 1989a,b; Handrock and Zeisberg, 1982; Hildesheimer et al., 1990; Zenner and Ernst, 1993; Zenner and Plinkert, 1992; Patuzzi and Thompson, 1991; Takeyama et al., 1992); (2) regulating the gain that the OHCs provide to establish sharp tuning at the receptor level, i.e. regulation of the 'cochlear amplifier' and thus the responsiveness and tuning of the IHCs (Carlier and Pujol, 1982; Brown and Nuttall, 1984; Kim, 1984,1986; Hubbard and Mountain, 1990; Zenner and Plinkert, 1992); (3) regulating OHC motility such that the ears do not ring in an uncontrolled fashion (Wilson, 1987; Veuillet et al., 1992a,b; Ch6ry-Croze et al., 1993); (4) improving the ability to process and perceive signals in noise, i.e. antimasking (Dewson, 1967; Dewson, 1968; Pickles and Comis, 1973; Gifford and Guinan, 1983; Dolan and Nuttall, 1988; Winslow and Sachs, 1987; Kawase and Liberman, 1993; Kawase et al., 1993); (5) regulating the set point of the basilar membrane, i.e. applying an adjustable bias to optimize signal perception according to the existing acoustic environment (LePage, 1989). On the basis of present study on the mustached bat we would also add regulation of the stiffness and damping of the cochlear partition and thus the resonance frequency and tonotopy along the partition. We prefer to refer to the cochlear partition as a whole rather than the basilar membrane because the changes are within the partition and the properties of the partition as a whole must be important in determining the vibratory properties of the membrane as a whole. Our data seem particularly congruent with the ideas advanced by Siegel and Kim (1982) who hypothesized that the cochlear partition damping can be controlled by an active mechanism that can account for the high

120

O.W. Henson, Jr. et al. /Hearing Research 86/1,2 (1995) 111-124

degree of frequency selectivity, sensitivity and mechanical nonlinearity in the cochlea. They proposed that the O H C s influence the sensitivity and frequency selectivity of the inner hair cells and their nerve fibers by affecting the dynamic range of motion of the cochlear partition. Their data correlate well with the known importance of the O H C s in establishing the response properties of the auditory nerve (Dallos and Harris, 1978). For the mustached bat, it is also clear that changes in the resonance properties not only affect the response properties of the afferent nerve fibers but also the bioacoustic behavior of the animal (Huffman and Henson, 1993a,b). Mustached bats use biosonar to find their way in darkness and to hunt flying insects in cluttered environments (Henson et al., 1987). Any of the above functions assigned to the e f f e r e n t - O H C system could provide the bat's sensitive ears with an internal control with distinct advantages, but further studies are needed to establish if and when the efferent system is active during pulse emission a n d / o r echo perception. One function which seems especially likely is protection. Mustached bats live in large colonies in tropical caves. H e r e active bats emit ultrasonic biosonar signals almost continuously and each pulse contains a harmonic series of constant frequency components (ca. 30, 60, 90 and 120 kHz); a harmonic series of frequency modulated components precede and follow the CF components. The SPL of emitted pulses is often greater than 100 dB. In addition, the bat roosts are filled with communication sounds that contain a rich array of frequencies in the 8 to 100 kHz band (Kanwal et al., 1994). Thus, there can be no question but that the ears of these animals are almost continuously b o m b a r d e d by a broad spectrum of intense sounds when they are in caves. Both ears would be exposed to sounds that would be considerably richer and more intense than the CLN used in our experiments. Intuitively, a major role of the well-developed medial efferent system in the mustached bat would seemingly be to dampen the vibrations of the cochlear partition in these noisy environments. The marked resonance of the ear seen with sound stimulation suggests that damping may be needed to prevent self destruction, Pollak et al. (1979) observed that the ears of mustached bats recovering from anesthesia can easily be overdriven by ca 61 kHz tones of brief duration and large threshold shifts occur for sounds at or near the resonance frequency of the ear. It is not unusual to find sustained resonance or loud spontaneous cochlear emissions in mustached bats (see K6ssl and Vater, 1985,1990). While it seems likely that a lack of efferent control might be responsible for these internally generated oscillations, more experiments are needed to assess and quantify changes in resonance and damping under conditions of medial

efferent disruptions. The concept of increased ringing with decreased efferent control is congruent with data suggesting that the lack of efferent suppression may be a cause of tinnitus (Wilson, 1987; Veuillet et al., 1991,1992a,1992b; ChEry-Croze et al., 1993), It is important to note however, that when we have used gentamicin to block the medial efferent system we have not seen indications of sustained resonance. Anatomical observations suggest that the efferent system plays more than a protective role. Particularly interesting is the anatomical diversity in efferent innervation patterns among mammals. In the mustached bat the medial efferent system is well represented throughout the cochlea, with each O H C having a single large efferent terminal. There is no selective increase in efferent innervation in the 60 kHz region but the average size of the efferent terminals is significantly larger in the constant frequency regions (Xie et al., 1993). Each fiber that crosses the tunnel to reach the O H C s innervates only a few (1-3) hair cells (Wilson et al., 1991; Henson et al., 1990a) and thus a very fine degree of control is expected; the fine gradation of changes in damping that the present work demonstrates is therefore not surprising. In other mammals, the efferents are often more heavily concentrated in specific regions, the size of the O H C patches that a single fiber innervates is relatively large, the first row of O H C s is more heavily innervated than the 2nd and 3rd rows, and the apical region of the cochlea may be devoid of efferent fibers (see Warr, 1992). Of interest is the complete lack of a medial efferent system in rhinolophid and hipposiderid bats (Bruns and Schmieszek, 1980; Bishop and Henson, 1988; D a n n h o f and Bruns, 1991; Vater et al., 1992). It seems contradictory to say that the medial efferent system is very important to hearing in one species and yet describe other species whose sense of hearing is just as sensitive and sharply tuned as Pteronotus parnellii, but whose ears have no O H C efferent innervation. One major difference between the ears of rhinolophids and Pteronotus parnellii is that the former lack the pronounced resonance and cochlear emissions that are characteristic of the mustached bat (Henson et al., 1985; K6ssl and Vater, 1990; K6ssl, 1992,1994a,1994b). In addition, the inner ear has anatomical (mechanical) specializations that are very different from the mustached bat (see Vater, 1988; Vater et al., 1992). Observations on the changes in resonance frequency with efferent activity were less clear than the decay time changes because the resonance frequency was SPL dependent. In theory, one would expect that any change in the stiffness of the cochlear partition would change the resonance frequency and that there would be concomitant tonotopic shifts (Huffman and Henson, 1993a,b); it is difficult to envision any perceptual benefit to rapid shifts in a system that must continuously

O.W. Henson, Jr. et aL /Hearing Research 86/1,2 (1995) 111-124

monitor a very complex, constantly changing acoustic environment and again we suggest that the loss of medial efferents and the associated development of other specializations in other Doppler-shift compensating bats may add a beneficial stability to the system.

Acknowledgements This work was supported by NIH grant NS-12445. We are grateful to Roya Rouhani for her work in developing the computer software that allowed us to rapidly measure decay time in the CM potential. We also thank Dr. David Smith, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, for his suggestions and interest in the gentamicin experiments.

References Berlin, C.I., Hood, L.J., Wen, H., Szabo, P., Cecola, R.P., Rigby, P. and Jackson, D.F. (1993) Contralateral suppression of non-linear click-evoked otoacoustic emissions. Hear. Res. 71, 1-11. Bishop, A.L. and Henson, O.W., Jr. (1987) The efferent cochlear projections of the superior olivary complex in the mustached bat. Hear. Res. 31, 175-182. Bishop, A.L. and Henson, O.W., Jr. (1988) The efferent auditory system in Doppler-shift compensating bats. In: P.E. Nachtigall, P.W.B. Moore (Eds.), Animal Sonar, Plenum Publishing Corporation, New York, 307-310. Brown, M.C. and Nuttall, A.L. (1984) Efferent control of cochlear inner hair cell responses in the guinea-pig. J. Physiol. 354, 625626. Brown, S.E. and Norton, S.J. (1990) The effects of contralateral acoustic stimulation on the acoustic distortion product, 2 fl-f2. Abstr. Assoc. Res. Otolaryngol. 13, 230. Brownell, W.E., Bader, C.R., Bertrand, D. and Ribaupierre, Y. (1985) Evoked mechanical responses of isolated cochlear outer hair cells. Science 227, 194-196. Bruns, V. and Schmieszek, E. (1980) Cochlear innervation in the greater horseshoe bat: Demonstration of an acoustic fovea. Hear. Res. 3, 27-43. Buno, W. (1978) Auditory nerve fiber activity influenced by contralateral ear sound stimulation. Exp. Neurol. 59, 62-74. Carlier, E. and Pujol, R. (1982) Sectioning the efferent bundle decreases cochlear frequency selectivity. Neurosci. Lett. 28, 101106. Ch6ry-Croze, S., Moulin, A. and Collet, L. (1993) Effect of contralateral sound stimulation on the distortion product 2fl-f2 in humans: Evidence of a frequency specificity. Hear. Res. 68, 53-58. Cody, A.R. and Johnstone, B.M. (1982) Acoustically evoked activity of single efferent neurons in the guinea pig cochlea. J. Acoust. Soc. Am. 72, 280-282. Collet, L., Kemp, D.T., Veuillet, E., Duclaux, R., Moulin, A. and Morgon, A. (1990a) Effect of contralateral auditory stimuli on active cochlear micro-mechanical properties in human subjects. Hear. Res. 43, 251-262.

121

Collet, L., Veuillet, E., Duclaux, R. and Morgon, A. (1990b) Influence of a contralateral auditory stimulation on evoked auditory stimulation on evoked otoacoustic emissions. In: F. Grandori, D.T. Kemp, G. Cianfrone (Eds.), Advances in Audiology, Karger, Basel, pp. 164-170. Collet, L., Veuillet, E., Bene, J. and Morgon, A. (1992) Effects of contralateral white noise on click-evoked emissions in normal and sensorineural ears: Towards an exploration of the medial olivocochlear system. Audiology 31, 1-7. Dallos, P. (1992) The active cochlea. J. Neurosci. 12, 4575-4585. Dallos, P., Evans, B.N. and Hallworth, R. (1991) On the nature of the motor element in electrokinetic shape changes of cochlear outer hair cells. Nature 350, 155-157. Dallos, P., Geisler, C.D., Matthews, J.W., Ruggero, M.M. and Steele, C.R. (1990) The Mechanisms and Biophysics of Hearing. Springer-Verlag, New York, pp. 1-418. Dallos, P. and Harris, D. (1978) Properties of auditory nerve responses in the absence of outer hair cells. J. Neurophysiol. 41, 365-383. Dancer, A. (1992) Experimental look at cochlear mechanics. Audiology 31, 301-312. Dannhof, B.J. and Bruns, V. (1991) The organ of corti in the bat Hipposideros bicolor. Hear. Res. 53, 253-268: Davis, H. (1983) An active process in cochlear mechanics. Hear. Res. 9, 79-90. de Boer, E. (1979) Short-wave world revisited: Resonance in a two-dimensional cochlear model. Hear. Res. 1,253-281. de Boer, E. (1990) Wave propagation, activity and frequency selectivity in the cochlea. Advances in Audiology 7, 1-12. Dewson III, J.H. (1967) Efferent olivocochlear bundle: Some relationships to noise masking and to stimulus attenuation. J. Neurophysiol. 30, 817-832. Dewson, J.H. (1968) Efferent olivocochlear bundle: Some relationships to stimulus discrimnation in noise. J. Neurophysiol. 31, 122-130. Dolan, D.F. and Nuttall, A.L. (1988) Masked cochlear whole-nerve response intensity functions altered by electrical stimulation of the crossed olivocochlear bundle. J. Acoust. Soc. Amer. 83, 1081-1086. Fex, J. (1962) Auditory activity in centrifugal and centripetal cochlear fibers in cat. Acta Physiol. Scand. 55 Suppl. 189, 1-68. Gifford, M.L. and Guinan, J.J., Jr. (1983) Effects of crossed-olivocochlear-bundle stimulation on cat auditory nerve fiber responses to tones. J. Acoust. Soc. Am. 74, 115-123. Gifford, M.L. and Guinan, J.J., Jr. (1987) Effects of electrical stimulation of medial olivocochlear neurons on ipsilateral and contralateral cochlear responses. Hear. Res. 29, 179-194. Guinan, J. (1986) Effect of efferent neural activity on cochlear mechanics. Scand. Audiol. Suppl. 25, 53-62. Handrock, M. and Zeisberg, J. (1982) The influence of the efferent system on adaptation, temporary and permanent threshold shift. Arch. Otorhinolaryngol. 234, 191-195. Harrison, W.A. and Burns, E.M. (1993) Effects of contralateral acoustic stimulation on spontaneous otoacoustic emissions. J. Acoust. Soc. Am. 94, 2649-2658. Henson, M.M. (1978) The basilar membrane of the bat, Pteronotusp. parnellii. Am. J. Anat. 153, 143-157. Henson, M.M. and Henson, O.W., Jr. (1991) Specializations for sharp tuning in the mustached bat: The tectorial membrane and spiral limbus. Hear. Res. 56, 122-132. Henson, O.W., Jr. and Henson, M.M. (1988) Morphometric analysis of cochlear structures in the mustached bat, Pteronotus parnellii parnellii. In: P.E. Nachtigall and P.W.B. Moore (Eds.), Animal Sonar, Plenum Publishing Corporation, New York, pp. 301-305. Henson, O.W. Jr. and Pollak, G.D. (1972) A technique for chronic implantation of electrodes in the cochleae of bats. Physiol. Behav. 8, 1185-1187.

122

O.W. Henson, Jr. et aL / Hearing Research 86 / 1, 2 (1995) 111-124

Henson, O.W. Jr., Bishop, A., Keating, A., Kobler, J., Henson, M., Wilson, B. and Hansen, R. (1987) Biosonar imaging of insects by Pteronotus p. parnellii, the mustached bat. Natl. Geographic Res. 3, 82-101. Henson, O.W., Jr., Keating, A. and Xie, D.-H. (1993) The effect of contralateral acoustic stimulation on cochlear resonance and damping. Abstr. Assoc Res. Otolaryngol. 16, 79. Henson, O.W., Jr., Koplas, P.A., Keating, A.W., Huffman, R.F. and Henson, M.M. (1990b) Cochlear resonance in the mustached bat: Behavioral adaptations. Hear. Res. 50, 259-274. Henson, O.W., Jr., Schuller, G. and Vater, M. (1985) A comparative study of the physiological properties of the inner ear in Doppler shift compensating bats (Rhinolophus rouxi and Pteronotus parnellii). J. Comp. Physiol. A. 157, 587-597. Henson, M.M., Wynne, R.H., Wilson, J.L. and Henson, O.W., Jr. (1990a) Distribution of crossed and uncrossed medial efferent fibers in the mustached bat. Abstr. Assoc Res. Otolaryngol. 13, 366-367. Henson, O.W., Jr., Xie, D.-H. and Keating, A.W. (1994) The effect of contralateral stimulation on the quality factor (Q) of the cochlear resonator. Abstr. Assoc Res. Otolaryngol. 17, 94. Hildesheimer, M., Makai, E., Muchnik, C. and Rubinstein, M. (1990) The influence of the efferent system on acoustic overstimulation. Hear. Res. 43, 263-268. Housley, G.D. and Ashmore, J.F. (1991) Direct measurement of the action of acetylcholine on isolated outer hair cells of the guinea pig cochlea. Proc. Royal Soc. Lond. 244, 160-167. Hubbard, A.E. and Mountain, D.C. (1990) Hair cell forward and reverse transduction: Differential suppression and enhancement. Hear. Res. 43, 269-272. Huffman, R.F. and Henson, O.W., Jr. (1993a) Labile cochlear tuning in the mustached bat. I. Concomitant shifts in biosonar emission frequency. J. Comp. Physiol. A 171, 725-734. Huffman, R.F. and Henson, O.W., Jr. (1993b) Labile cochlear tuning in the mustached bat. II. Concomitant shifts in neural tuning. J. Comp. Physiol. A 171, 735-748. Kanwal, J.S., Matsumura, S., Ohlemiller, K. and Suga, N. (1994) Analysis of acoustic elements in syntax in communication sounds emitted by mustached bats. J. Acoust. Soc. Am. 96, 1229-1254. Karlsson, K.K., Ulfendahl, M., Khanna, S.M. and Flock, A. (1991) The effects of quinine on the cochlear mechanics in the isolated temporal bone preparation. Hear. Res. 53, 95-100. Kashiwamura, M., Satoh, N., Fukuda, S., Kawanami, M., Chida, E. and Inuyama, Y. (1993) (Changes in human spontaneous otoacoustic emissions with contralateral acoustic stimulation) (English translation). Nippon Jibiinkoka Gakkai Kaiho. 96, 922-930. Kawase, T. and Liberman, M.C. (1993) Antimasking effects of the olivocochlear reflex. 1. Enhancement of compound action potentials to masked tones. J. Neurophysiol. 70, 2519-2532. Kawase, T., Delgutte, B. and Liberman, M.C. (1993) Antimasking effects of the olivoeochlear reflex. 2. Enhancement of auditorynerve response to masked tones. J. Neurophysiol. 70, 2533-2549. Kim, D.O. (1984) Functional roles of the inner- and outer-hair-cell subsystems in the cochlea and brainstem. In: C.I. Berlin (Ed.), Hearing Science: Recent Advances, College-Hill Press, San Diego, pp. 241-262. Kim, D.O. (1986) Active and nonlinear cochlear biomechanics and the role of outer-hair-cell subsystem in the mammalian auditory system. Hear. Res. 22, 105-114. Kirk, D.L. and Johnstone, B.M. (1993) Modulation of f2-f1: Evidence for a GABA-ergic efferent system in apical cochlea of the guinea pig. Hear. Res. 67, 20-34. K6ssl, M. (1992) High-frequency two-tone distortions from the ear of the mustached bat, Pteronotus parnellii reflect enhanced cochlear tuning. Naturwissenschaften 79, 425-427.

K6ssl, M. (1994a) Otoacoustic emissions from the cochlea of the 'constant frequency' bats, Pteronotus parnellii and Rhinolophus rouxi. Hear. Res. 72, 59-72. K6ssl, M. (1994b) Evidence for a mechanical filter in the cochlea of the 'constant frequency' bats, Rhinolophus rouxi and Pteronotus parnellii. Hear. Res. 72, 73-80. K6ssl, M. and Vater, M. (1985) Evoked acoustic emissions and cochlear microphonics in the mustache bat, Pteronotus parnellii. Hear. Res. 19, 157-170. K6ssl, M. and Vater, M. (1990) Resonance phenomena in the cochlea of the mustache bat and their contribution to neuronal response characteristics in the cochlear nucleus. J. Comp. Physiol. A 166, 711-720. Kujawa, S.G., Glattke, T.J., Fallon, M. and Bobbin, R.P. (1993) Contralateral sound suppresses distortion product otoacoustic emissions through cholinergic mechanisms. Hear. Res. 68, 97-106. LePage, E.L. and Johnstone, B.M. (1980) Nonlinear mechanical behaviour of the basilar membrane in the basal turn of the guinea pig cochlea. Hear. Res. 2, 183-189. LePage, E.L. (1989) Functional role of the olivo-cochlear bundle: A motor unit control system in the mammalian cochlea. Hear. Res. 38, 177-198. LePage, Eric L. (1990) Helmholtz revisited: Direct mechanical data suggest a physical model for dynamic control of mapping frequency to place along the cochlear partition. In: P. Dallos, C.D. Geisler, J.W. Matthews, M.A. Ruggero, C.R. Steele (Eds.), The Mechanics and Biophysics of Hearing, Lecture Notes in Biomathematics, Springer-Verlag, New York, pp. 278-287. Liberman, M.C. (1989) Rapid assessment of sound-evoked olivocochlear feedback: suppression of compound action potentials by contralateral sound. Hear. Res. 38, 47-56. Liberman, M.C. (1991) The olivocochlear efferent bundle and the susceptibility of the inner ear to acoustic injury. J. Neurophysiol. 65, 123-132. Maurer, J., Beck, A,, Mann, W. and Mintert, R. (1992) Veranderungen otoakustischer Emissionen unter gleichzeitiger Beschallung des Gegenohres bei Normalpersonen und bei Patienten mit einseitigem Akustikusneurinom. Laryngorhinootologie 71, 69-73. Moiler, A.R. (1970) Studies of the damped oscillatory response of the auditory frequency analyzer. Acta Physiol. Scand. 78, 299-314. Morant-Ventura, A., Marco-Algarra, J., Caballero-Mallea, J., OrtsAlborch, M. and Perez-del-Valle, B. (1993) Utilidad de las otoemisiones ac'usticas provocadas en el estudio del reflejo olivo-coclear (The usefulness of provoked acoustic otoemissions in the study of olivo-cochlear reflex). An. Otorrinolaringol. Ibero Am. 20, 423-434. Mott, J.B., Norton, S.J., Neely, S.T. and Warr, W.B. (1989) Changes in spontaneous otoacoustic emissions produced by acoustic stimulation of the contralateral ear. Hear. Res. 38, 229-242. Mountain, D. (1980) Changes in endolymphatic potential and crossed olivocochlear bundle stimulation alter cochlear mechanics. Science 210, 71-72. Mountain, D.C. and Hubbard, A.E. (1994) A piezoelectric model of outer hair cell function. J. Acoust. Soc. Am. 95, 350-354. Neely, S.T. (1993) A model of cochlear mechanics with outer hair cell motility. J. Acoust. Soc. Am. 94, 137-146. Neely, S.T. and Kim, D.O. (1983) An active cochlear model showing sharp tuning and high sensitivity. Hear. Res. 9, 123-130. Norman, M. and Thornton, A.R.D. (1993) Frequency analysis of the contralateral suppression of evoked otoacousfic emissions by narrow-band noise. Brit. J. Audiol. 27, 281-289. Patuzzi, R. and Rajan, R. (1990) Does electrical stimulation of the crossed olivo-cochlear bundle produce movement of the organ of Corti? Hear. Res. 45, 15-32. Patuzzi, R.B. and Thompson, M.L. (1991) Cochlear efferent neu-

O.W. Henson, Jr. et al. /Hearing Research 86/1,2 (1995) 111-124 rones and protection against acoustic trauma: Protection of outer hair cell receptor current and interanimal variability. Hear. Res. 54, 45-58. Pickles, J.O. and Comis, S.D. (1973) Role of centrifugal pathways to cochlear nucleus in detection of signals in noise. J. Neurophysiol. 36, 1131-1137. Plinkert, P.K. and Lenarz, T. (1992) Evozierte otoakustische Emissionen und ihre Beeinflussung durch kontralaterale akustische Stimulation. Laryngorhinootologie 71, 74-78. Plinkert, P.K., Zenner, H.P. and Heilbronn, E. (1991) A nicotinic acetylcholine receptor-like alpha-bungarotoxin-binding site on outer hair cells. Hear. Res. 53, 123-130. Pollak, G., Henson, O.W., Jr. and Johnson, R. (1979) Multiple specializations in the peripheral auditory system of the CF-FM bat, Pteronotus parnellii. J. Comp. Physiol. A 131, 255-266. Puel, J.-L. and Rebillard, G. (1990) Effect of contralateral sound stimulation on the distortion product 2F1-F2: Evidence that the medial efferent system is involved. J. Acoust. Soc. Am. 87, 1630-1635. Puel, J.-L., Bobbin, R.P. and Fallon, M. (1988) An ipsilateral cochlear effferent loop protects the cochlea during intense sound exposure. Hear. Res. 37, 65-70. Rajan, R. (1988a) Effect of electrical stimulation of the crossed olivocochlear bundle on temporary threshold shifts in auditory sensitivity. I. Dependence on electrical stimulation parameters. J. Neurophysiol. 60, 549-568. Rajan, R. (1988b) Effect of electrical stimulation of the crossed olivocochlear bundle on temporary threshold shifts in auditory sensitivity. II. Dependence on the level of temporary threshold shifts. J. Neurophysiol. 60, 569-579. Rajan, R. and Johnstone, B.M. (1983) Efferent effects elicited by electrical stimulation at the round window of the guinea pig. Hear. Res. 12, 405-417. Rajan, R. and Johnstone, B.M. (1988) Electrical stimulation of cochlear efferents at the round window reduces auditory desensitization in guinea pigs. II. Dependence on level of temporary threshold shifts. Hear. Res. 36, 75-88. Rajan, R., Robertson, D. and Johnstone, B.M. (1990) Absence of tonic activity of the crossed olivocochlear bundle in determining compound action potential thresholds, amplitudes and masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities. Hear Res. 44, 195-208. Rhode, W.S. (1974) Measurement of vibration of the basilar membrane in the squirrel monkey. Ann. Otol. Rhinol. Laryngol. 83, 619-625. Rossi, T., Actis, R., Solero, P. Rolando, M. and Pejrone, M.D. (1993) Cochlear interdependence and micromechanics in man and their relations with the activity of the medial olivocochlear efferent system (MOES). J. Laryngol. Otol. 107, 883-891. Ruggero, M.A. and Rich, N.C. (1991) Application of a commercially-manufactured Doppler-shift laser velocimeter to the measurement of basilar-membrane vibration. Hear. Res. 51, 215-230. Ruggero, M.A., Robles, L., Rich, N.C. and Recio, A. (1992) Basilar membrane responses to two-tone and broadband stimuli. Philos. Trans. Roy. Soc. Lond. [B] 336, 307-315. Siegel, J.H. and Kim, D.O. (1982) Efferent neural control of cochlear mechanics? Olivocochlear bundle stimluation affects cochlear biomechanical nonlinearity. Hear. Res. 6, 171-182. Slepecky, N., Ulfendahl, M. and Flock, A. (1988) Shortening and elongation of isolated outer hair cells in response to application of potassium gluconate, acetylcholine and cationized ferritin. Hear. Res. 34, 119-126. Smith, D.W., Erre, J.-P. and Aran, J.-M. (1994) Rapid, reversible

123

elimination of medial olivocochlear efferent function following single injections of gentamicin in the guinea pig. Brain Res. 652, 243-248. Sziklai, I. and Dallos, P. (1993) Acetylcholine controls the gain of the voltage-to-movement converter in isolated outer hair cells. Acta Otolaryngol. (Stockh) 113, 326-329. Takeyama, M., Kusakari, J., Nishikawa, N. and Wada, T. (1992) The effect of crossed olivo-cochlear bundle stimulation on acoustic trauma. Acta Otolaryngol. (Stockh) 112, 205-209. Vater, M., Lenoir, M. and Pujol, R. (1992) Ultrastructure of the horseshoe bat's organ of Corti. II. Transmission electron microscopy. J. Comp. Neurol. 318, 380-391. Vater, M. (1988) Lightmicroscopic observations on cochlear development in horseshoe bats (Rhinolophus rouxi). In: P.E. Nachtigall, P.W.B. Moore (Eds.), Animal Sonar, Plenum Press, New York, pp. 341-345. Veuillet, E., Collet, L., Distant, F. and Morgon, A. (1992a) Tinnitus and medial cochlear efferent system. In: J.M. Arah, R. Dauman (Eds.), Tinnitus 91, Kugler, Amsterdam, pp. 205-209. Veuillet, E., Collet, L. and Morgon, A. (1992b) Differential effects of ear-canal pressure and contralateral acoustic stimulation on evoked otoacoustic emissions in humans. Hear. Res. 61, 47-55. Veuillet, E., Collet, L. and Duclaux, R. (1991) Effect of contralateral acoustic stimulation on active cochlear micromechanical properties in human subjects: Dependence on stimulus variables. J. Neurophysiol. 65, 724-735. Warr, W.B. (1992) Organization of olivocochlear efferent systems in mammals. In: D.B. Webster, A.N. Popper, R.R. Fay (Eds.), Mammalian Auditory Pathway: Neuroanatomy, Springer Handbook of Auditory Research, Springer-Verlag, New York, pp. 410-448. Warren, E.H. III and Liberman, M.C. (1989a) Effects of coutralateral sound on auditory-nerve responses. I. Contributions of cochlear efferents. Hear. Res. 37, 89-104. Warren, E.H. III and Liberman, M.C. (1989b) Effects of contralateral sound on auditory-nerve responses. II. Dependence on stimulus variables. Hear. Res. 37, 105-122. Wiederhold, M.L. (1970) Variations in the effects of electrical stimulation of the crossed olivocochlear bundle on cat single auditory nerve fiber responses to tone bursts. J. Acoust. Soc. Am. 48, 966-977. Wiederhold, M.L. (1986) Physiology of the olivocochlear system. In: R.A. Altschuler, R.P. Bobbin, D.W. Hoffman (Eds.), Neurobiology of Hearing: The Cochlea, Raven Press, New York, pp. 349-370. Wiederhold, M.L. and Kiang, N.Y.-S. (1970) Effects of electrical stimulation of the crossed olivocochlear bundle on single auditory nerve fibers in the cat. J. Acoust. Soc. Am. 48, 950-965. Williams, E.A., Brookes, G.B. and Prasher, D.K. (1993) Effects of contralateral acoustic stimulation on otoacoustic emissions following vestibular neurectomy. Scand. Audiol. 22, 197-203. Wilson, J.L., Henson, M.M. and Henson, O.W., Jr. (1991) Course and distribution of efferent fibers in the cochlea of the mouse. Hear. Res. 55, 98-108. Wilson, J.P. (1987) Theory of tinnitus generation. In: J.P. Hazell (Ed.), Tinnitus, Livingstone, Edinburgh, pp. 20-45. Winslow, R.L. and Sachs, M.B. (1987) Effect of electrical stimulation of the crossed olivocochlear bundle on auditory nerve response to tones in noise. J. Neurophysiol. 57, 1002-1021. Xie, D.H., Henson, M.M., Bishop, A.L. and Henson, O.W., Jr. (1993) Efferent terminals in the cochlea of the mustached bat: Quantitative data. Hear. Res. 66, 81-90. Zenner, H.-P. (1993) Possible roles of outer hair cell d.c. movements in the cochlea. Brit. J. Audiol. 27, 73-77.

124

O.W. Henson, Jr. et al. /Hearing Research 86 / 1,2 (1995) 111-124

Zenner, H.P. and Ernst, A. (1993) Sound preprocessing by ac and dc movements of cochlear outer hair cells. Prog. Brain Res. 97, 21-30. Zenner, H.P. and Plinkert, P.K. (1992) A.C. and D.C. motility of mammalian auditory sensory cells-a new concept in hearing physiology. Otolaryngol. Pol. 46, 333-349. Zwislocki, J.J. (1980) Five decades of research on cochlear mechanics. J. Acoust. Soc. Amer. 67, 1679-1685.

Zwislocki, J.J. (1983) Some current concepts of cochlear mechanics. Audiology 22, 517-529. Zwislocki, J.J. (1984) Biophysics of the mammalian ear. In: W.W. Dawson, J.M. Enoch (Eds.), Foundations of Sensory Science, Springer-Verlag, Berlin, pp. 109-150. Zwislocki, J.J. (1986) Analysis of cochlear mechanics. Hear. Res. 22, 155-169.