The effects of age and sex on the detection of pure tones by adult CBA/CaJ mice (Mus musculus)

Abstract

Age-related hearing loss (ARHL) is a neurodegenerative disorder characterized by a gradual decrease in hearing sensitivity. Previous electrophysiological and behavioral studies have demonstrated that the CBA/CaJ mouse strain is an appropriate model for the late-onset hearing loss found in humans. However, few studies have characterized hearing in these mice behaviorally using longitudinal methodologies. The goal of this research was to utilize a longitudinal design and operant conditioning procedures with positive reinforcement to construct audiograms and temporal integration functions in aging CBA/CaJ mice. In the first experiment, thresholds were collected for 8, 16, 24, 42, and 64 kHz pure tones in 30 male and 35 female CBA/CaJ mice. Similar to humans, mice had higher thresholds for high frequency tones than for low frequency pure tones across the lifespan. Female mice had better hearing acuity than males after 645 days of age. In the second experiment, temporal integration functions were constructed for 18 male and 18 female mice for 16 and 64 kHz tones varying in duration. Mice showed an increase in thresholds for tones shorter than 200 ms, reaching peak performance at shorter durations than other rodent species. Overall, CBA/CaJ mice experience ARHL for pure tones of different frequencies and durations, making them a good model for studies on hearing loss. These findings highlight the importance of using a wide range of stimuli and a longitudinal design when comparing presbycusis across different species.

Keywords: age-related hearing loss; audiogram; operant conditioning; psychoacoustics.

Figure 1.

Schematic of the experimental setup used in both experiments. Mice began a trial by nose poking to the observation hole. When they detected a stimulus presented from the speaker, they poked to the report hole. If correct, the mice received Ensure® from the dipper.

Figure 2.

Second order polynomial regression plots for 8, 16, 24, 42, and 64 kHz tones (a-e). Each plot depicts thresholds from multiple mice across their lifespans (males = filled blue symbols, females = open symbols). Lines represent the best data fits of hearing across the lifespan for 8–64 kHz (a-e). The amount of variability in the data explained by aging is expressed in the form of r² for males and females separately.

Figure 3.

Mean audiograms with standard error bars as predicted by the model for male (a) and female (b) subjects under 300 d.o. (300 = grey circles), 301–450 d.o. (450 = red squares), and 451–645 d.o. (645 = pink stars), 645–750 d.o. (750 = green hexagons), 751–900 d.o. (900 = blue diamonds), and 901–1000 d.o. (1000 = black circles). Hearing between male and female mice significantly diverged around 645 d.o..

Figure 4.

Second order polynomial regression plots for 20, 50, 200, 400, and 800 ms, 16 and 64 kHz tones (a-e). Each plot depicts thresholds from multiple mice across their lifespans (males = filled blue symbols, females = open symbols). Lines represent the best data fit of hearing across the lifespan for 16 kHz (solid lines, blue = males, black = females) and 64 kHz (dashed lines, blue = male, black = females). The amount of variability in the data explained by aging is expressed in the form of r² for each frequency and for males and females separately.

Figure 5.

Mean temporal summation functions with standard deviation error bars (a) and average threshold shifts relative to the longest duration signal (dashed line) as a function of signal duration (b) for male (blue symbols, blue line) and female (open symbols, black lines) mice. These data are potted in comparison to mean temporal summation functions and threshold shifts for 15 kHz (green triangles, green line) and 60 kHz (purple triangles, purple line) for young male NMRI mice retrieved from Ehret (1976b). In CBA/CaJ mice, the greatest change in threshold shifts occurs between 20 and 200 ms (dotted line).