Brief cochlear excitotoxicity produces temporary neural swelling and transient deficits in auditory sensitivity; however, the consequences of long-lasting excitotoxic insult have not been tested. Chronic intra-cochlear infusion of the glutamate agonist AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) resulted in functional deficits in the sound-evoked auditory brainstem response, as well as in behavioral measures of hearing. The electrophysiological deficits were similar to those observed following acute infusion of AMPA into the cochlea; however, the concentration-response curve was significantly shifted as a consequence of the slower infusion rate used with chronic cochlear administration. As observed following acute excitotoxic insult, complete functional recovery was evident within 7 days of discontinuing the AMPA infusion. Distortion product otoacoustic emissions were not affected by chronic AMPA infusion, suggesting that trauma to outer hair cells did not contribute to AMPA-induced deficits in acoustic sensitivity. Results from the current experiment address the permanence of deficits induced by chronic (14 day) excitotoxic insult as well as deficits in psychophysical detection of longer duration acoustic signals.
REFERENCES
1.
Altschuler, R. A., Raphael, Y., Prosen, C. A., Dolan, D. F., and Moody, D. B. (1992). “Acoustic stimulation and overstimulation in the cochlea: A comparison between basal and apical turns of the cochlea,” in Noise-Induced Hearing Loss, edited by A. L. Dancer, D. Henderson, R. J. Salvi, and R. P. Hamernik (Mosby Year Book, St. Louis), pp. 60–72.
2.
Billett
, T. E.
, Thorne
, P. R.
, and Gavin
, J. B.
(1989
). “The nature and progression of injury in the organ of Corti during ischemia
,” Hear. Res.
41
, 189
–197
.3.
Bledsoe
, Jr., S. C.
, Bobbin
, R. P.
, and Chihal
, D. M.
(1981
). “Kainic acid: an evaluation of its action on cochlear potentials
,” Hear. Res.
4
, 109
–120
.4.
Borg
, E.
, and Engstrom
, B.
(1983
). “Hearing thresholds in the rabbit. A behavioral and electrophysiological study
,” Acta Otorhinolaryngol. (Stockh)
95
, 19
–26
.5.
Brown
, J. N.
, Miller
, J. M.
, Altschuler
, R. A.
, and Nuttall
, A. L.
(1993
). “Osmotic pump implant for chronic infusion of drugs into the inner ear
,” Hear. Res.
70
, 167
–172
.6.
Canlon
, B.
, and Fransson
, A.
(1995
). “Morphological and functional preservation of the outer hair cells from noise trauma by sound conditioning
,” Hear. Res.
84
, 112
–124
.7.
Duan
, M. L.
, and Canlon
, B.
(2001
). “Short-term adaptation in the peripheral auditory system is related to the AMPA receptor
,” Acta Otorhinolaryngol. (Stockh)
121
, 21
–27
.8.
Eybalin
, M.
(1993
). “Neurotransmitters and neuromodulators of the mammalian cochlea
,” Physiol. Rev.
73
, 309
–373
.9.
Frolenkov
, G. I.
, Belyantseva
, I. A.
, Kurc
, M.
, Mastroianni
, M. A.
, and Kachar
, B.
(1998
). “Cochlear outer hair cell electromotility can provide force for both low and high intensity distortion product otoacoustic emissions
,” Hear. Res.
126
, 67
–74
.10.
Garbe, C. M., Prieskorn, D. M., Bledsoe, S. C., Jr., and Moody, D. B. (1997). “Behavioral and electrophysiological assessment of changes in hearing following chronic AMPA-induced excitotoxicity,” in 20th Midwinter Meeting of the Association for Research in Otolaryngology, edited by G. R. Popelka (Association for Research in Otolaryngology, St. Petersburg Beach, FL), p. 109.
11.
Gerken
, G. M.
, Bhat
, V. K.
, and Hutchison-Clutter
, M.
(1990
). “Auditory temporal integration and the power function model
,” J. Acoust. Soc. Am.
88
, 767
–778
.12.
Gil-Loyzaga
, P.
, Hernandez-Ortiz
, M. J.
, Rodriguez-Benito
, T.
, and Lasso de la Vega
, M. L.
(1993
). “Diltiazem protects against neurotoxicity induced by excitotoxic amino acids on cochlear afferent fibers
,” ORL. J. Otorhinolaryngol. Relat. Spec.
55
(4
), 211
–215
.13.
Gil-Loyzaga
, P.
, and Pujol
, R.
(1990
). “Neurotoxicity of kainic acid in the rat cochlea during early developmental stages
,” Eur. Arch. Otorhinolaryngol.
248
, 40
–48
.14.
Gorga
, M. P.
, Beauchaine
, K. A.
, Reiland
, J. K.
, Worthington
, D. W.
, and Javel
, E.
(1984
). “The effects of stimulus duration on ABR and behavioral thresholds
,” J. Acoust. Soc. Am.
76
, 616
–619
.15.
Green
, D. M.
, Birdsall
, T. G.
, and Tanner
, W. P. J.
(1957
). “Signal detection as a function of signal intensity and duration
,” J. Acoust. Soc. Am.
29
, 523
–531
.16.
Greenwood
, D. D.
(1961
). “Critical bandwidth and the frequency coordinates of the basilar membrane
,” J. Acoust. Soc. Am.
33
, 1344
–1356
.17.
Greenwood
, D. D.
(1990
). “A cochlear frequency-position function for several species—29 years later
,” J. Acoust. Soc. Am.
87
, 2592
–2605
.18.
Harrison
, R. V.
(1998
). “An animal model of auditory neuropathy
,” Ear Hear.
19
, 355
–361
.19.
Jakobsen
, B.
, and Zimmer
, J.
(2001
). “Chronic exposure of kainate and NBQX changes AMPA toxicity in hippocampal slice cultures
,” NeuroReport
12
, 3593
–3597
.20.
Janssen
, R.
, Schweitzer
, L.
, and Jensen
, K. F.
(1991
). “Glutamate neurotoxicity in the developing rat cochlea: physiological and morphological approaches
,” Brain Res.
552
, 255
–264
.21.
Jenison
, G. L.
, and Bobbin
, R. P.
(1985
). “Quisqualate excites spiral ganglion neurons of the guinea pig
,” Hear. Res.
20
, 261
–265
.22.
Jenison
, G. L.
, Winbery
, S.
, and Bobbin
, R. P.
(1986
). “Comparative actions of quisqualate and N-methyl-D-aspartate, excitatory amino acid agonists, on guinea-pig cochlear potentials
,” Comp. Biochem. Physiol. C
84
, 385
–389
.23.
Juiz
, J. M.
, Rueda
, J.
, Merchan
, J. A.
, and Sala
, M. L.
(1989
). “The effects of kainic acid on the cochlear ganglion of the rat
,” Hear. Res.
40
, 65
–74
.24.
Kraus
, N.
, Bradlow
, A. R.
, Cheatham
, M. A.
, Cunningham
, J.
, King
, C. D.
, Koch
, D. B.
, Nicol
, T. G.
, McGee
, T. J.
, Stein
, L. K.
, and Wright
, B. A.
(2000
). “Consequences of neural asynchrony: a case of auditory neuropathy
,” J. Assoc. Res. Otolaryngol.
1
, 33
–45
.25.
Lalwani
, A. K.
, Walsh
, B. J.
, Reilly
, P. G.
, Muzyczka
, N.
, and Mhatre
, A. N.
(1996
). “Development of in vivo gene therapy for hearing disorders: introduction of adeno-associated virus into the cochlea of the guinea pig
,” Gene Ther.
3
, 588
–592
.26.
Le Prell, C. G., Bledsoe, S. C., Jr., Bobbin, R. P., and Puel, J. L. (2001). “Neurotransmission in the inner ear: Functional and molecular analyses,” in Physiology of the Ear, edited by J. Santos-Sacchi (Singular Publishing, New York), pp. 575–611.
27.
Le Prell, C. G., Bledsoe, S. C., Jr., and Moody, D. B. (1999a). “Deficits in tone-evoked operant and electrophysiological responses during chronic AMPA-induced excitotoxicity,” in 22nd Midwinter Meeting of the Association for Research in Otolaryngology, edited by G. R. Popelka (Association for Research in Otolaryngology, St. Petersburg Beach, FL), p. 164.
28.
Le Prell, C. G., Yagi, M., Beyer, L. A., Bledsoe, S. C., Jr., Raphael, Y., and Moody, D. B. (1999b). “Morphological trauma accompanying ABR-assessed deficits in hearing following chronic AMPA-induced excitotoxicity,” in 22nd Midwinter Meeting of the Association for Research in Otolaryngology, edited by G. R. Popelka (Association for Research in Otolaryngology, St. Petersburg Beach, FL), p. 164.
29.
Li
, D.
, Henley
, C. M.
, and O’Malley
, Jr., B. W.
(1999
). “Distortion product otoacoustic emissions and outer hair cell defects in the hyt/hyt mutant mouse
,” Hear. Res.
138
, 65
–72
.30.
Liberman, M. C., and Mulroy, M. J. (1982). “Acute and chronic effects of acoustic trauma: Cochlear pathology and auditory nerve pathophysiology,” in New Perspectives on Noise-Induced Hearing Loss, edited by R. P. Hamernik, D. Henderson, and R. J. Salvi (Raven Press, New York).
31.
Luebke
, A. E.
, Steiger
, J. D.
, Hodges
, B. L.
, and Amalfitano
, A.
(2001
). “A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function
,” Gene Ther.
8
, 789
–794
.32.
Matute
, C.
(1998
). “Characteristics of acute and chronic kainate excitotoxic damage to the optic nerve
,” Proc. Natl. Acad. Sci. U.S.A.
95
, 10229
–10234
.33.
McFadden
, S. L.
, Henderson
, D.
, and Shen
, Y. H.
(1997
). “Low-frequency ‘conditioning’ provides long-term protection from noise-induced threshold shifts in chinchillas
,” Hear. Res.
103
, 142
–150
.34.
Miller
, C. A.
, Woodruff
, K. E.
, and Pfingst
, B. E.
(1995
). “Functional responses from guinea pigs with cochlear implants. I. Electrophysiological and psychophysical measures
,” Hear. Res.
92
, 85
–99
.35.
Mills
, D. M.
, Loos
, B. M.
, and Henley
, C. M.
(1999
). “Increased susceptibility of male rats to kanamycin-induced cochleotoxicity
,” Hear. Res.
128
, 75
–79
.36.
Minami
, T.
, Matsumura
, S.
, Okuda-Ashitaka
, E.
, Shimamoto
, K.
, Sakimura
, K.
, Mishina
, M.
, Mori
, H.
, and Ito
, S.
(2001
). “Characterization of the glutamatergic system for induction and maintenance of allodynia
,” Brain Res.
895
, 178
–185
.37.
Monaghan
, D. T.
, Bridges
, R. J.
, and Cotman
, C. W.
(1989
). “The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system
,” Annu. Rev. Pharmacol. Toxicol.
29
, 365
–402
.38.
Musiek
, F. E.
(1982
). “ABR in eighth-nerve and brain-stem disorders
,” Am. J. Otol.
3
, 243
–248
.39.
National Research Council (1996). Guide for the Care and Use of Laboratory Animals, National Academy Press, Washington, D.C.
40.
Nielsen
, E. O.
, Schousboe
, A.
, Hansen
, S. H.
, and Krogsgaard-Larsen
, P.
(1985
). “Excitatory amino acids: studies on the biochemical and chemical stability of ibotenic acid and related compounds
,” J. Neurochem.
45
, 725
–731
.41.
Niemiec, A. J., and Moody, D. B. (1995). “Constant Stimulus and Tracking Procedures for Measuring Sensitivity,” in Methods in Comparative Psychoacoustics, Vol. 6, edited by G. M. Klump, R. J. Dooling, R. R. Fay, and W. C. Stebbins (Birkhauser Verlag, Basel, Switzerland), pp. 65–77.
42.
O’Brien
, R. J.
, Kamboj
, S.
, Ehlers
, M. D.
, Rosen
, K. R.
, Fischbach
, G. D.
, and Huganir
, R. L.
(1998
). “Activity-dependent modulation of synaptic AMPA receptor accumulation.
” Neuron
21
, 1067
–1078
.43.
Ohyama
, K.
, Salt
, A. N.
, and Thalmann
, R.
(1988
). “Volume flow rate of perilymph in the guinea-pig cochlea
,” Hear. Res.
35
, 119
–129
.44.
Ozdamar
, O.
, and Stein
, L.
(1981
). “Auditory brain stem response (ABR) in unilateral hearing loss
,” Laryngoscope
91
, 565
–574
.45.
Parks
, T. N.
(2000
). “The AMPA receptors of auditory neurons
,” Hear. Res.
147
, 77
–91
.46.
Prieskorn
, D. M.
, and Miller
, J. M.
(2000
). “Technical report: chronic and acute intracochlear infusion in rodents
,” Hear. Res.
140
, 212
–215
.47.
Prosen
, C. A.
, Petersen
, M. R.
, Moody
, D. B.
, and Stebbins
, W. C.
(1978
). “Auditory thresholds and kanamycin-induced hearing loss in the guinea pig assessed by a positive reinforcement procedure
,” J. Acoust. Soc. Am.
63
, 559
–566
.48.
Puel
, J. L.
(1995
). “Chemical synaptic transmission in the cochlea
,” Prog. Neurobiol.
47
, 449
–476
.49.
Puel
, J. L.
, d’Aldin
, C.
, Ruel
, J.
, Ladrech
, S.
, and Pujol
, R.
(1997
). “Synaptic repair mechanisms responsible for functional recovery in various cochlear pathologies
,” Acta Otorhinolaryngol. Belg.
117
, 214
–218
.50.
Puel
, J. L.
, Pujol
, R.
, Ladrech
, S.
, and Eybalin
, M.
(1991
). “Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid electrophysiological and neurotoxic effects in the guinea-pig cochlea
,” Neuroscience
45
, 63
–72
.51.
Puel
, J. L.
, Pujol
, R.
, Tribillac
, F.
, Ladrech
, S.
, and Eybalin
, M.
(1994
). “Excitatory amino acid antagonists protect cochlear auditory neurons from excitotoxicity
,” J. Comp. Neurol.
341
, 241
–256
.52.
Puel
, J. L.
, Ruel
, J.
, Gervais d’Aldin
, C.
, and Pujol
, R.
(1998
). “Excitotoxicity and repair of cochlear synapses after noise-trauma induced hearing loss
,” NeuroReport
9
, 2109
–2114
.53.
Puel
, J. L.
, Saffiedine
, S.
, Gervais d’Aldin
, C.
, Eybalin
, M.
, and Pujol
, R.
(1995
). “Synaptic regeneration and functional recovery after excitotoxic injury in the guinea pig cochlea
,” C. R. Acad. Sci. III
318
, 67
–75
.54.
Pujol
, R.
, Lenoir
, M.
, Robertson
, D.
, Eybalin
, M.
, and Johnstone
, B. M.
(1985
). “Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells
,” Hear. Res.
18
, 145
–151
.55.
Pujol
, R.
, Rebillard
, G.
, Puel
, J. L.
, Lenoir
, M.
, Eybalin
, M.
, and Recasens
, M.
(1990
). “Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or anoxic conditions occurring in ageing
,” Acta Otorhinolaryngol. Belg.
476
, 32
–36
.56.
Robertson
, D.
(1983
). “Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea
,” Hear. Res.
9
, 263
–278
.57.
Rothman
, S.
(1984
). “Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death
,” J. Neurosci.
4
, 1884
–1891
.58.
Ruel
, J.
, Bobbin
, R. P.
, Vidal
, D.
, Pujol
, R.
, and Puel
, J. L.
(2000
). “The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea
,” Neuropharmacology
39
, 1959
–1973
.59.
Ruel
, J.
, Chen
, C.
, Pujol
, R.
, Bobbin
, R. P.
, and Puel
, J. L.
(1999
). “AMPA-preferring glutamate receptors in cochlear physiology of adult guinea-pig
,” J. Physiol. (Paris)
518
, 667
–680
.60.
Salt
, A. N.
, and Ma
, Y.
(2001
). “Quantification of solute entry into cochlear perilymph through the round window membrane
,” Hear. Res.
154
, 88
–97
.61.
Salvi
, R. J.
, Wang
, J.
, Ding
, D.
, Stecker
, N.
, and Arnold
, S.
(1999
). “Auditory deprivation of the central auditory system resulting from selective inner hair cell loss: animal model of auditory neuropathy
,” Scand. Audiol. Suppl.
51
, 1
–12
.62.
Skellett
, R. A.
, Cullen
, Jr., J. K.
, Fallon
, M.
, and Bobbin
, R. P.
(1998
). “Conditioning the auditory system with continuous vs. interrupted noise of equal acoustic energy: is either exposure more protective?
,” Hear. Res.
116
, 21
–32
.63.
Spoendlin
, H.
(1971
). “Primary structural changes in the organ of Corti after acoustic overstimulation
,” Acta Otorhinolaryngol. Belg.
71
, 166
–176
.64.
Starr
, A.
, Picton
, T. W.
, Sininger
, Y.
, Hood
, L. J.
, and Berlin
, C. I.
(1996
). “Auditory neuropathy
,” Brain
119
, 741
–753
.65.
Starr
, A.
, Sininger
, Y. S.
, and Pratt
, H.
(2000
). “The varieties of auditory neuropathy
,” J. Basic Clin. Physiol. Pharmacol.
11
, 215
–230
.66.
Sun
, H.
, Salvi
, R. J.
, Ding
, D. L.
, Hashino
, D. E.
, Shero
, M.
, and Zheng
, X. Y.
(2000
). “Excitotoxic effect of kainic acid on chicken otoacoustic emissions and cochlear potentials
,” J. Acoust. Soc. Am.
107
, 2136
–2142
.67.
Szymanski
, M. D.
, Bain
, D. E.
, Kiehl
, K.
, Pennington
, S.
, Wong
, S.
, and Henry
, K. R.
(1999
). “Killer whale (Orcinus orca) hearing: auditory brainstem response and behavioral audiograms
,” J. Acoust. Soc. Am.
106
, 1134
–1141
.68.
Turrigiano
, G. G.
(1999
). “Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same
,” Trends Neurosci.
22
, 221
–227
.69.
Turrigiano
, G. G.
, and Nelson
, S. B.
(1998
). “Thinking globally, acting locally: AMPA receptor turnover and synaptic strength [comment]
,” Neuron
21
, 933
–935
.70.
Wang
, Y.
, Hirose
, K.
, and Liberman
, M. C.
(2002
). “Dynamics of noise-induced cellular injury and repair in the mouse cochlea
,” J. Assoc. Res. Otolaryngol.
3
, 248
–268
.71.
Watkins
, J. C.
, Krogsgaard-Larsen
, P.
, and Honore
, T.
(1990
). “Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists
,” Trends Pharmacol. Sci.
11
, 25
–33
.72.
Watson
, C. S.
, and Gengel
, R. W.
(1969
). “Signal duration and signal frequency in relation to auditory sensitivity
,” J. Acoust. Soc. Am.
46
, 989
–997
.73.
Wolski
, L. F.
, Anderson
, R. C.
, Bowles
, A. E.
, and Yochem
, P. K.
(2003
). “Measuring hearing in the harbor seal (Phoca vitulina): Comparison of behavioral and auditory brainstem response techniques
,” J. Acoust. Soc. Am.
113
, 629
–637
.74.
Worthington
, D. W.
, and Peters
, J. F.
(1980
). “Quantifiable hearing and no ABR: paradox or error?
,” Ear Hear.
1
, 281
–285
.75.
Yoshida
, N.
, and Liberman
, M. C.
(2000
). “Sound conditioning reduces noise-induced permanent threshold shift in mice
,” Hear. Res.
148
, 213
–219
.76.
Zheng
, X. Y.
, Henderson
, D.
, Hu
, B. H.
, and McFadden
, S. L.
(1997
). “Recovery of structure and function of inner ear afferent synapses following kainic acid excitotoxicity
,” Hear. Res.
105
, 65
–76
.77.
Zheng
, X. Y.
, McFadden
, S. L.
, and Henderson
, D.
(1998
). “Faster recovery in central than in peripheral auditory system following a reversible cochlear deafferentation
,” Neuroscience
85
, 579
–586
.78.
Zheng
, X. Y.
, Salvi
, R. J.
, McFadden
, S. L.
, Ding
, D. L.
, and Henderson
, D.
(1999
). “Recovery of kainic acid excitotoxicity in chinchilla cochlea
,” Ann. N.Y. Acad. Sci.
884
, 255
–269
.79.
Zheng
, X. Y.
, Wang
, J.
, Salvi
, R. J.
, and Henderson
, D.
(1996
). “Effects of kainic acid on the cochlear potentials and distortion product otoacoustic emissions in chinchilla
,” Hear. Res.
95
, 161
–167
.
This content is only available via PDF.
© 2004 Acoustical Society of America.
2004
Acoustical Society of America
You do not currently have access to this content.
