Minimal Effects of Age and Exposure to a Noisy Environment on Hearing in Alpha9 Nicotinic Receptor Knockout Mice

Abstract

Studies have suggested a role of weakened medial olivocochlear (OC) efferent feedback in accelerated hearing loss and increased susceptibility to noise. The present study investigated the progression of hearing loss with age and exposure to a noisy environment in medial OC-deficient mice. Alpha9 nicotinic acetylcholine receptor knockout (α9KO) and wild types were screened for hearing loss using auditory brainstem responses. α9KO mice housed in a quiet environment did not show increased hearing loss compared to wild types in young adulthood and middle age. Challenging the medial OC system by housing in a noisy environment did not increase hearing loss in α9KO mice compared to wild types. ABR wave 1 amplitudes also did not show differences between α9KO mice and wild types. These data suggest that deficient medial OC feedback does not result in early onset of hearing loss.

Keywords: age; alpha9 nicotinic acetylcholine receptor; auditory efferent; hearing loss; noise; olivocochlear.

Figure 1

Example of a click-evoked ABR recorded from a wild type mouse housed in quiet. Thresholds were estimated by recording responses to a descending level series of stimuli, calculating the maximum peak-to-peak amplitude (any peak) within a 10-ms window starting at 2-ms after the onset of the stimuli, and determining the sound level that produced a response that was 2 standard deviations about the average baseline noise recorded in a 5-ms window at the end of each recording epoch. The waveform latency is not corrected for the travel time between the speaker and the ear. The amplitude of the first positive (p1) to the first negative (n1) peaks were also calculated.

Figure 2

Distribution of ABR click and tone thresholds in four groups of 1–5 month old mice: wild type mice housed in quiet (WT-Q), wild type mice housed in noisy conditions (WT-N), olivocochlear-deficient alpha9 nicotinic acetylcholine receptor knockout mice housed in quiet (α9KO-Q), alpha9 nicotinic acetylcholine receptor knockout mice housed in noisy conditions (α9KO-N). Horizontal lines inside the boxplots represent the median. Dots represent the 5th and 95th percentiles. Thick black lines and asterisks indicate statistically significant differences identified with post-hoc analysis. Thresholds are shown for click (A), 8 kHz (B), 16 kHz (C), and 32 kHz (D).

Figure 3

Distribution of ABR click and tone thresholds in four groups of 6–10 month old mice: wild type mice housed in quiet (WT-Q), wild type mice housed in noisy conditions (WT-N), olivocochlear-deficient alpha9 nicotinic acetylcholine receptor knockout mice housed in quiet (α9KO-Q), alpha9 nicotinic acetylcholine receptor knockout mice housed in noisy conditions (α9KO-N). Horizontal lines inside the boxplots represent the median. Dots represent the 5th and 95th percentiles. Thresholds are shown for click (A), 8 kHz (B), 16 kHz (C), and 32 kHz (D).

Figure 4

Distribution of ABR click and tone thresholds in four groups of 11–15 month old mice: wild type mice housed in quiet (WT-Q), wild type mice housed in noisy conditions (WT-N), olivocochlear-deficient alpha9 nicotinic acetylcholine receptor knockout mice housed in quiet (α9KO-Q), alpha9 nicotinic acetylcholine receptor knockout mice housed in noisy conditions (α9KO-N). Horizontal lines inside the boxplots represent the median. Dots represent the 5th and 95th percentiles. Thresholds are shown for click (A), 8 kHz (B), 16 kHz (C), and 32 kHz (D).

Figure 5

Distribution of ABR wave 1 amplitudes for clicks and tones in four groups of 1–5 month old mice: wild type mice housed in quiet (WT-Q), wild type mice housed in noisy conditions (WT-N), olivocochlear-deficient alpha9 nicotinic acetylcholine receptor knockout mice housed in quiet (α9KO-Q), alpha9 nicotinic acetylcholine receptor knockout mice housed in noisy conditions (α9KO-N). Horizontal lines inside the boxplots represent the median. Dots represent the 5th and 95th percentiles. Wave amplitudes are shown for click (A), 8 kHz (B), 16 kHz (C), and 32 kHz (D).

Figure 6

Distribution of ABR wave 1 amplitudes for clicks and tones in four groups of 11–15 month old mice: wild type mice housed in quiet (WT-Q), wild type mice housed in noisy conditions (WT-N), olivocochlear-deficient alpha9 nicotinic acetylcholine receptor knockout mice housed in quiet (α9KO-Q), alpha9 nicotinic acetylcholine receptor knockout mice housed in noisy conditions (α9KO-N). Horizontal lines inside the boxplots represent the median. Dots represent the 5th and 95th percentiles. Thick black lines and asterisks indicate statistically significant differences identified with post-hoc analysis. Wave amplitudes are shown for click (A), 8 kHz (B), 16 kHz (C), and 32 kHz (D).