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J Neurophysiol 93: 643-655, 2005. First published September 29, 2004; doi:10.1152/jn.00160.2004
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TRANSLATIONAL PHYSIOLOGY

Effects of Intratympanic Gentamicin on Vestibular Afferents and Hair Cells in the Chinchilla

Timo P. Hirvonen1,4, Lloyd B. Minor1,2,3, Timothy E. Hullar1,5 and John P. Carey1

1Department of Otolaryngology-Head and Neck Surgery, 2Department of Biomedical Engineering, and 3Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland; 4Department of Otolaryngology, Helsinki University Central Hospital, Helsinki, Finland; and 5Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri

Submitted 20 February 2004; accepted in final form 22 September 2004

Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5–25 (early) or 90–115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P < 0.001) on the treated side (early: 44.3 ± 16.3; late: 33.9 ± 13.2 spikes·s–1) than on the untreated side (54.9 ± 16.8 spikes·s–1). Spontaneous rates of irregular and intermediate afferents did not change. The majority of treated afferents did not measurably respond to tilt or rotation (82% in the early group, 76% in the late group). Those that did respond had abnormally low sensitivities (P < 0.001). Treated canal units that responded to rotation had mean sensitivities only 5–7% of the values for untreated canal afferents. Treated otolith afferents had mean sensitivities 23–28% of the values for untreated otolith units. Sensitivity to externally applied galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.


Address for reprint requests and other correspondence: J. P. Carey, Dept. of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Univ. School of Medicine, 601 North Caroline St., 6th Floor, Baltimore, MD 21287-0910 (E-mail: jcarey{at}jhmi.edu)




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