Effect of Selective Carboplatin-Induced Inner Hair Cell Loss on Temporal Integration in Chinchillas.

Abstract

Integration of acoustic information over time is essential for processing complex stimuli, such as speech, due to its continuous variability along the time domain. In both humans and animals, perception of acoustic stimuli is a function of both stimulus intensity and duration. For brief acoustic stimuli, as duration increases, thresholds decrease by approximately 3dB for every doubling in duration until stimulus duration reaches 500ms, a phenomenon known as temporal integration. Although hearing loss and damage to outer hair cells (OHC) have been shown to alter temporal integration in some studies, the role of cochlear inner hair cells (IHC) on temporal integration is unknown. Because IHC transmit nearly all acoustic information to the central auditory system and are believed to code both intensity and timing information, these sensory cells likely play a critical role in temporal integration. To test the hypothesis that selective IHC loss degrades the temporal integration function, behaviorally trained chinchillas were treated with carboplatin, a drug known to selectively destroy IHC with little to no effect on OHC in this species. Pure-tone thresholds were assessed across frequencies (1, 2, 4, 8, 12kHz) as a function of signal duration (500, 100, 50, 10, and 5ms). Baseline testing showed a significant effect of duration on thresholds. Threshold decreased as a function of increasing duration, as expected. Carboplatin treatment (75mg/kg) produced a moderate to severe loss of IHC (45-85%) with little-to-no loss of OHC. Contrary to our hypothesis, post-carboplatin temporal integration thresholds showed no significant differences from baseline regardless of stimulus duration or frequency. These data suggest that few IHC are necessary for temporal integration of simple stimuli. Temporal integration may be sensitive to loss of OHC and loss of cochlear non-linearities but does not appear to be sensitive to selective IHC loss.