Multiple-unit threshold curves (MTCs) were obtained from inferior colliculus (IC) neurons across much of the (approximately 2-2.5 yr) life-span of two inbred mouse strains: the C57BL/6, which undergoes progressive age-related sensorineural hearing loss; and the CBA, which maintains good sensitivity until well into the second year of life. Tonotopic organization (the orderly dorsoventral arrangement of frequency sensitivity) is disrupted in the IC central nucleus (ICC) of aging C57 mice. Dorsal (low-frequency) MTCs change little during the first year of life, but in more ventral (high-frequency) regions high-frequency portions of MTCs are eliminated, best frequencies become lower, and low-frequency thresholds are reduced. These changes make the curves more similar to one another along the dorsoventral axis. During the second year of life, all thresholds become greatly elevated with neurons throughout the IC responding only to middle frequencies at very high intensities. In C57 mice, Q10 ratios (a measure of MTC tip sharpness) decline after 7 mo. The decline of Q10 with aging is associated with the age-related lowering of best frequencies and elevation of thresholds, both of which are positively correlated with smaller Q10s. The frequency range of C57 MTCs begins to decrease at 14 mo of age, when hearing loss is quite severe at all frequencies. In CBA mice, the above changes are minimal or do not occur even in 22 mo olds, which have moderate loss of sensitivity across all frequencies. Even in young mice (prior to demonstrable cochlear pathology in C57 mice), there are differences in MTCs between the two strains employed, with sensitivity of CBA mice being "shifted" toward higher frequencies. Age-related changes in MTC properties depend on the pattern of hearing loss (e.g., high frequency vs. flat) and the dorsoventral location of neurons within the ICC.
Genetics of Peripheral Vestibular Dysfunction: Lessons from Mutant Mouse Strains