**4.1.1 Age-dependent changes of ABR thresholds**

Age-related hearing loss in gerbils was first reported by Henry et al. (1980), showing 15-20 dB threshold elevation for frequencies between 1 and 32 kHz in 2 year old as compared to 3 month old gerbils. Mills et al. (1990) derived ABR thresholds for gerbils between 8 and 36 months of age that were raised in a low-noise environment. Thresholds in 3 year old gerbils varied over a wide range; some old animals showed no or only small threshold elevation compared to young controls, while some old gerbils had more than 50 dB hearing loss. Hearing loss was less than 10 dB in a group of 19 month old gerbils, increased to 10-20 dB at 2 years and further progressed with age. Mean threshold shift at 3 years was approximately 20 dB for the 1-4 kHz range and 25-30 dB for higher frequencies. Threshold shift determined by ABR and CAP measurements in 3 year old gerbils showed a good correspondence.

## **4.1.2 Age-dependent changes of ABR growth functions**

Boettcher et al. (1993a) compared wave ii-iii and wave iv ABR input-output functions of young and old gerbils. The plots of wave ii-iii and iv amplitude as a function of the tone pip level showed a reduction in old as compared to young gerbils that was not directly related to threshold. This was seen through the response amplitude of the best old gerbils with near normal thresholds being greatly reduced at high stimulus levels, especially for the lower test

The Mongolian Gerbil as a Model for

around 20 dB in the 4-8 kHz region (Mills et al., 1997).

the Analysis of Peripheral and Central Age-Dependent Hearing Loss 77

gerbils were exposed monaurally to a 3.5 kHz tone with 113 dBSPL for 1 hour. Pilot experiments had shown that this exposure was associated with a permanent threshold shift

In the first study (Mills et al., 1997), pre-exposure thresholds for both ears were determined in 18 month old gerbils. Thresholds for the exposed and the non-exposed ears were reevaluated six weeks (age 19-20 months) after the exposure and at an age of 3 years. Preexposure thresholds at the age of 18 months were similar for both ears. Six weeks following the exposure, thresholds of the unexposed ears were similar to pre-exposure thresholds while thresholds of the exposed ears were clearly elevated at 4 and 8 kHz. Comparing the pre-exposure thresholds determined at an age of 18 months and thresholds at 3 years of age for the unexposed ears in this sample showed a relatively small age-dependent increase of 10-13 dB across the whole frequency range (this sample had excellent high frequency hearing compared to data previously presented in Mills et al., 1990). The threshold difference between exposed and unexposed ears was 15 and 12 dB for 4 kHz and 8 kHz 6 weeks following exposure and decreased to 11 and 6 dB in 3 year old gerbils. The additional age-dependent threshold loss in the exposed ear was smaller than in the unexposed ear.

In the second study (Boettcher, 2002b), ABR thresholds were determined for groups of 6-8 and 34-38 month old gerbils before and 30 days following sound exposure to evaluate the effect of age on the susceptibility to acoustic trauma. Pre-exposure thresholds of the 17 old gerbils in this study were exceptionally low, and were only 5-9 dB higher than pre-exposure thresholds of 17 young gerbils across the frequency range tested. Threshold shift (elevation above pre-exposure threshold) induced by the sound exposure was very similar for both age groups below 16 kHz. It was 6 dB or less at 1 and 2 kHz and 15-18 dB at 4 and 8 kHz. Only at 16 kHz was the threshold loss in old gerbils (17dB) higher than in young (9 dB) gerbils. Thus, except for the high frequency region, susceptibility to acoustic trauma in relatively

Boettcher et al. (1996) analysed the CAP and ABR responses to two successive 50 ms broadband noise pulses at 60 and 80 dBSPL as a function of the time interval (gap; 2, 4, 8, 16 and 32 ms) between the two noise pulses in young and old gerbils. This design corresponds to the gap detection paradigm in psychoacoustic studies, where the duration of the smallest detectable gap is used as a measure of auditory temporal resolution. The CAP and ABR analysis compared the onset responses to the first and second noise pulse as a function of gap duration. ABR thresholds for tone pips between 1 and 16 kHz were elevated by 10-15 dB in the group of 10 old (33-38 months) as compared to 9 young (4-8 months) gerbils, indicating only a moderate degree of peripheral hearing loss. Consistent with previous CAP (Hellstrom & Schmiedt, 1990) and ABR (Boettcher et al., 1993a) studies, the amplitudes of the potentials evoked by the noise bursts were reduced in old gerbils. In both age groups, the response amplitude to the onset of the second noise pulse decreased with decreasing gap duration, while the response amplitude to the first pulse was independent of gap duration. To compare the recovery of the response with increasing gap duration between the two age groups, despite the reduced response amplitude in old gerbils, the ratio of the response to the second burst divided by the response to the first burst was used. The ratio was smallest for the 2 ms gap duration. For the CAP, the response to the onset of the second

normal hearing old gerbils was not higher than in young gerbils.

**4.1.6 ABR and CAP for characterising auditory temporal resolution** 

frequencies. The reduction in response amplitude to high stimulus levels was more pronounced at lower test frequencies, while ABR threshold elevation was more pronounced at the higher test frequencies. As a consequence of the reduced ABR response amplitudes, the slopes of the ABR growth functions were also reduced in old gerbils. Boettcher et al. (1993a) discussed that a loss of spiral ganglion cells could lead to a similar reduction in CAP and ABR amplitudes. However, Keithley et al. (1989) reported a significant reduction in spiral ganglion cell density only for the most basal portion of the cochlea (20 kHz region), while the reduction of ABR response amplitude in old gerbils appeared more pronounced at frequencies ≤ 4 kHz. In addition to ganglion cell loss, ABR response amplitude may be affected by a reduction of the EP or a reduction in the degree of synchronisation of the response across the population of auditory neurons. The reduction of ABR amplitude was prominent in old gerbils and largely independent of threshold elevation (Boettcher, 2002a).

#### **4.1.3 Age-dependent changes of ABR response latencies**

Boettcher et al. (1993b) compared wave i, ii and iv response latency between young and old gerbils with different degrees of threshold shift. In the group of normal hearing old gerbils, they found no increase in response latency. Instead, response latency appeared reduced at 8 and 16 kHz for wave i and ii and at all frequencies for wave iv. The reduction was small for wave i and increased for wave iv, resulting in reduced i-iv intervals in normal hearing old as compared to young gerbils. In gerbils with hearing loss, ABR latencies were prolonged at low stimulus levels and normal at high stimulus levels for wave i and ii. Response latency for wave iv in old gerbils with hearing loss was increased for all stimulus levels at 1 and 2 kHz and appeared normal at higher frequencies. Boettcher et al. (1993b) suggested that the decreasing latency along the auditory pathway in normal hearing old gerbils does not reflect changes originating in the periphery, but could rather reflect age-dependent changes in the central auditory system (e.g. loss of inhibition).

#### **4.1.4 The effect of low- and high-pass maskers on ABR thresholds**

ABR measurements have also been used to characterise masking of the response to tone pips by continuous low-pass (< 1 kHz) and high-pass (> 8 kHz) noise-maskers presented at an overall level of 80 dBSPL in young and old gerbils (Boettcher et al. 1995). Threshold shifts for the high-pass masker were similar for young and old gerbils. The shift of the quiet threshold in old gerbils was correlated with the shift of the masked threshold (relative to the mean quiet and masked threshold of young gerbils respectively) for 2 kHz and 4 kHz. For the low-pass masker, old gerbils, especially those with low ABR thresholds in the quiet condition, showed excessive masking compared to young gerbils. Threshold shift in old gerbils in the quiet condition was not correlated with the shift in the presence of the lowpass masker. These data suggest excess upward spread of masking in old as compared to young gerbils: the low-pass masker affected or spread to more basal (higher frequency) cochlear regions in old gerbils, even when ABR thresholds in quiet were near normal.

#### **4.1.5 The interaction of age and acoustic trauma analysed by ABR thresholds**

The interaction of noise-induced and age-dependent hearing loss has been analysed by ABR threshold measurements in gerbils (Boettcher, 2002b; Mills et al., 1997). Anaesthetised

frequencies. The reduction in response amplitude to high stimulus levels was more pronounced at lower test frequencies, while ABR threshold elevation was more pronounced at the higher test frequencies. As a consequence of the reduced ABR response amplitudes, the slopes of the ABR growth functions were also reduced in old gerbils. Boettcher et al. (1993a) discussed that a loss of spiral ganglion cells could lead to a similar reduction in CAP and ABR amplitudes. However, Keithley et al. (1989) reported a significant reduction in spiral ganglion cell density only for the most basal portion of the cochlea (20 kHz region), while the reduction of ABR response amplitude in old gerbils appeared more pronounced at frequencies ≤ 4 kHz. In addition to ganglion cell loss, ABR response amplitude may be affected by a reduction of the EP or a reduction in the degree of synchronisation of the response across the population of auditory neurons. The reduction of ABR amplitude was prominent in old gerbils and largely independent of threshold elevation (Boettcher, 2002a).

Boettcher et al. (1993b) compared wave i, ii and iv response latency between young and old gerbils with different degrees of threshold shift. In the group of normal hearing old gerbils, they found no increase in response latency. Instead, response latency appeared reduced at 8 and 16 kHz for wave i and ii and at all frequencies for wave iv. The reduction was small for wave i and increased for wave iv, resulting in reduced i-iv intervals in normal hearing old as compared to young gerbils. In gerbils with hearing loss, ABR latencies were prolonged at low stimulus levels and normal at high stimulus levels for wave i and ii. Response latency for wave iv in old gerbils with hearing loss was increased for all stimulus levels at 1 and 2 kHz and appeared normal at higher frequencies. Boettcher et al. (1993b) suggested that the decreasing latency along the auditory pathway in normal hearing old gerbils does not reflect changes originating in the periphery, but could rather reflect age-dependent changes in the

ABR measurements have also been used to characterise masking of the response to tone pips by continuous low-pass (< 1 kHz) and high-pass (> 8 kHz) noise-maskers presented at an overall level of 80 dBSPL in young and old gerbils (Boettcher et al. 1995). Threshold shifts for the high-pass masker were similar for young and old gerbils. The shift of the quiet threshold in old gerbils was correlated with the shift of the masked threshold (relative to the mean quiet and masked threshold of young gerbils respectively) for 2 kHz and 4 kHz. For the low-pass masker, old gerbils, especially those with low ABR thresholds in the quiet condition, showed excessive masking compared to young gerbils. Threshold shift in old gerbils in the quiet condition was not correlated with the shift in the presence of the lowpass masker. These data suggest excess upward spread of masking in old as compared to young gerbils: the low-pass masker affected or spread to more basal (higher frequency) cochlear regions in old gerbils, even when ABR thresholds in quiet were near normal.

**4.1.5 The interaction of age and acoustic trauma analysed by ABR thresholds** 

The interaction of noise-induced and age-dependent hearing loss has been analysed by ABR threshold measurements in gerbils (Boettcher, 2002b; Mills et al., 1997). Anaesthetised

**4.1.3 Age-dependent changes of ABR response latencies** 

central auditory system (e.g. loss of inhibition).

**4.1.4 The effect of low- and high-pass maskers on ABR thresholds** 

gerbils were exposed monaurally to a 3.5 kHz tone with 113 dBSPL for 1 hour. Pilot experiments had shown that this exposure was associated with a permanent threshold shift around 20 dB in the 4-8 kHz region (Mills et al., 1997).

In the first study (Mills et al., 1997), pre-exposure thresholds for both ears were determined in 18 month old gerbils. Thresholds for the exposed and the non-exposed ears were reevaluated six weeks (age 19-20 months) after the exposure and at an age of 3 years. Preexposure thresholds at the age of 18 months were similar for both ears. Six weeks following the exposure, thresholds of the unexposed ears were similar to pre-exposure thresholds while thresholds of the exposed ears were clearly elevated at 4 and 8 kHz. Comparing the pre-exposure thresholds determined at an age of 18 months and thresholds at 3 years of age for the unexposed ears in this sample showed a relatively small age-dependent increase of 10-13 dB across the whole frequency range (this sample had excellent high frequency hearing compared to data previously presented in Mills et al., 1990). The threshold difference between exposed and unexposed ears was 15 and 12 dB for 4 kHz and 8 kHz 6 weeks following exposure and decreased to 11 and 6 dB in 3 year old gerbils. The additional age-dependent threshold loss in the exposed ear was smaller than in the unexposed ear.

In the second study (Boettcher, 2002b), ABR thresholds were determined for groups of 6-8 and 34-38 month old gerbils before and 30 days following sound exposure to evaluate the effect of age on the susceptibility to acoustic trauma. Pre-exposure thresholds of the 17 old gerbils in this study were exceptionally low, and were only 5-9 dB higher than pre-exposure thresholds of 17 young gerbils across the frequency range tested. Threshold shift (elevation above pre-exposure threshold) induced by the sound exposure was very similar for both age groups below 16 kHz. It was 6 dB or less at 1 and 2 kHz and 15-18 dB at 4 and 8 kHz. Only at 16 kHz was the threshold loss in old gerbils (17dB) higher than in young (9 dB) gerbils. Thus, except for the high frequency region, susceptibility to acoustic trauma in relatively normal hearing old gerbils was not higher than in young gerbils.
