MIT HST 722J - Elevated Fusiform Cell Activity in the Dorsal Cochlear Nucleus of Chinchillas

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Elevated Fusiform Cell Activity in the Dorsal Cochlear Nucleus ofChinchillas with Psychophysical Evidence of TinnitusT. J. Brozoski,1C. A. Bauer,1and D. M. Caspary21Division of Otolaryngology, Head and Neck Surgery and2Department of Pharmacology, Southern Illinois UniversitySchool of Medicine, Springfield, Illinois 62702Chinchillas with psychophysical evidence of chronic tinnituswere shown to have significantly elevated spontaneous activityand stimulus-evoked responses in putative fusiform cells of thedorsal cochlear nuclei (DCN). Chinchillas were psychophysi-cally trained and tested before and after exposure to a trau-matic unilateral 80 dB (sound pressure level) 4 kHz tone. Beforeexposure, two groups were matched in terms of auditory dis-crimination performance (noise, and 1, 4, 6, and 10 kHz tones).After exposure, a single psychophysical difference emergedbetween groups. The exposed group displayed enhanced dis-crimination of 1 kHz tones ( p ⫽ 0.00027). Postexposure dis-crimination of other stimuli was unaffected. It was hypothesizedthat exposed animals experienced a chronic subjective tone(i.e., tinnitus), resulting from their trauma, and that features ofthis subjective tone were similar enough to 1 kHz to affectdiscrimination of 1 kHz objective signals. After psychophysicaltesting, single-unit recordings were obtained from each ani-mal’s DCN fusiform cell layer. Putative fusiform cells of exposedanimals showed significantly ( p ⫽ 0.0136) elevated spontane-ous activity, compared with cells of unexposed animals. Puta-tive fusiform cells of exposed animals showed a greaterstimulus-evoked response to tones at 1 kHz ( p ⫽ 0.0000006)and at characteristic-frequency ( p ⫽ 0.0000009). This in-creased activity was more pronounced on the exposed side. Noincrease in stimulus-evoked responses was observed to otherfrequencies or noise. These parallel psychophysical and elec-trophysiological results are consistent with the hypothesis thatchronic tonal tinnitus is associated with, and may result from,trauma-induced elevation of activity of DCN fusiform cells.Key words: tinnitus; acoustic trauma; psychophysical animalmodel; dorsal cochlear nucleus; fusiform cells; neural plasticityThirty-five percent of the population of the United States expe-riences tinnitus, a subjective “ringing in the ears” (US, 1967);10% of these consider their symptoms to be severe and disabling(Cooper, 1994). The most common causes of tinnitus are age-related hearing loss and hearing loss secondary to noise trauma.Noise-induced hearing loss typically becomes evident in middleage, and the associated tinnitus is present for a significant portionof an individual’s life. Despite the prevalence and morbidity oftinnitus, the pathophysiology of the disorder is poorly under-stood, and there is no generally accepted cure or treatment. Thislack of understanding stems from the difficulty of studying aperceptual state with no objective stimulus correlate and thattinnitus may arise from diverse combinations of peripheral andcentral pathologies (Murai et al., 1992).Following the work of Jastreboff et al. (1988), we developed apsychophysical animal model of tinnitus to investigate the disor-der in controlled experiments, where the cause is known and thepopulation sample is homogeneous (Bauer and Brozoski, 2001).A conditioned-suppression method was used to quantify the sen-sation of tinnitus in rats (Jastreboff et al., 1988). Unilateral acous-tic trauma was used to induce tinnitus, and continuous free-operant lever pressing for food reinforcement was used tomeasure chronic tinnitus over weeks to months. Using this modelin rats, tinnitus can be psychophysically distinguished from simplehearing loss, and the tinnitus can be partially reversed using aGABA analog (Bauer and Brozoski, 2001). This model can alsobe used to measure qualitative aspects of tinnitus.Recent studies suggest that tinnitus may result from inappro-priate plastic changes in the auditory pathway in response toacoustic trauma (Potashner et al., 1997; Kaltenbach et al., 2000;Milbrandt et al., 2000). Consistent with this hypothesis is evi-dence that aberrant neural activity in the dorsal cochlear nucleus(DCN) might underlie the generation of tinnitus. In patientssuffering from somatic craniocervical tinnitus, Levine (1999) hy-pothesized the likely involvement of the DCN. Zhang and Kalt-enbach (1998) and Kaltenbach and Afman (2000) have measuredelevated multiunit activity in the DCN of rats and hamsters afteracoustic trauma. They observed that the spontaneous DCN hy-peractivity evoked by previous noise exposure was similar to theresponse to low-to-moderate-intensity tone stimuli. Melamed etal. (2000) reported that selective outer hair cell loss induced bycisplatin resulted in increased spontaneous DCN activity. Thepreceding studies established that abnormal DCN activity oc-curred in subjects after acoustic trauma but did not establish aconnection between tinnitus and abnormal activity in the DCN.The present controlled experiments were designed to investigatethis association using chinchillas, a widely studied animal modelof human auditory processing (Clark, 1991). Fusiform cells werestudied because there is evidence for plasticity in this cell typeafter noise exposure and in aging (Kaltenbach et al., 1998; Schat-teman et al., 2000). Fusiform cells form the primary output of theDCN projecting via the dorsal acoustic stria to the contralateralReceived Dec. 28, 2001; revised Dec. 28, 2001; accepted Jan. 2, 2002.This work was supported by National Institutes of Health Grants DC96-003 andDC00-151. We thank Andrew Feltovich for assistance in data analysis.Correspondence should be addressed to T. J. Brozoski, Department of Surgery,Division of Otolaryngology, Head and Neck Surgery, 801 North Rutledge, SouthernIllinois University School of Medicine, Springfield, IL 62702. E-mail:[email protected] © 2002 Society for Neuroscience 0270-6474/02/222383-08$15.00/0The Journal of Neuroscience, March 15, 2002, 22(6):2383–2390inferior colliculus (Osen, 1972; Romand and Avan, 1997; Ali-bardi, 2000).MATERIALS AND METHODSSubjects. Twelve, young adult male chinchillas (Moulton ChinchillaFarm, Rochester, MN), were individually housed and maintained at 25°Cwith a 12 hr reversed light/dark schedule. Complete data were obtainedfrom eight animals: two animals died before completion of the study, andtwo were eliminated from the study because of poor behavioral


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