**4.2.5 The inferior colliculus (IC)**

80 Hearing Loss

The neurons of the MNTB are glycinergic. They convert the excitatory input from the contra-lateral VCN to inhibitory glycinergic projections predominantly to MSO and LSO. A light microscopic analysis of glycine immunoreacted sections showed that spongiform lesions, like those previously described for the CN, were very prominent in the MNTB of 3 year old gerbils, but were almost absent in 1 year old gerbils (Gleich & Strutz, 2002). Thus, spongiform lesions in MNTB develop with a delay of approximately 1-2 years compared to the CN. Spongiform lesions in old gerbils showed a gradient along the MNTB, decreasing from caudal towards rostral. The volume of MNTB was independent of age, as there was no shrinkage of the MNTB in old gerbils. In addition, there was no significant loss of glycinergic neurons in old as compared to young gerbils. In young and old gerbils, there was a systematic gradient of MNTB neuron size: MNTB neurons were largest in the ventrolateral and smallest in the dorso-medial part of MNTB. According to the tonotopic organisation of MNTB, low-frequency neurons appeared larger on average than highfrequency neurons. Comparing soma size of young and old gerbils revealed a homogenous reduction of cross-sectional area by approximately 20% throughout the MNTB in old gerbils, without any indication that the shrinkage of neurons varied with the tonotopic organisation of MNTB. The reduced size of MNTB neurons in old gerbils may lead to a reduced glycinergic input into MSO and LSO (and other nuclei receiving input from MNTB) and

The light microscopic analysis of GABA and glycine immunostained sections through the LSO in gerbils revealed that this nucleus was rather resistant to age-dependent changes (Gleich et al., 2004). Although Ostapoff & Morest (1989) had reported the presence of microcysts in the LSO of 1-2 year old gerbils, we found no or only small lesions in the LSO of 7 gerbils over 3 years of age. Only 4 old gerbils showed more-prominent lesions that were mainly restricted to the medial (high frequency) limb of LSO, although all 11 old gerbils in this sample had prominent lesions in the MNTB. Thus, LSO appeared more resistant to the formation of spongiform lesions than the MNTB. Neither the rostro-caudal extension, nor the cross-sectional area of LSO varied with age, demonstrating that the LSO did not shrink in old gerbils. In addition, the number of neurons in Nissl stained sections, as well as the number of GABA- and glycine-immunoreactive neurons did not change with age: there was no loss of neurons in the LSO of old gerbils. The density of inhibitory neurons showed the same gradient along the tonotopic representation of the LSO in young and old gerbils: GABAergic and glycinergic neurons were more prominent in the low as compared to the high-frequency limb. The comparison of the size of inhibitory neurons revealed that the cross sectional area of GABAergic and glycinergic LSO neurons was not affected by age in the lateral low-frequency limb, while there was a significant reduction (≈ 30%) in the medial high-frequency limb. Overall, the LSO showed only limited age-related changes that were

The neurons of the MSO do not express GABA or glycine, but MSO was well recognised in sections through the gerbil brainstem that were immunostained with antibodies against

**4.2.2 The medial nucleus of the trapezoid body (MNTB)** 

consequently affect processing of binaural stimuli.

**4.2.3 The lateral superior olive (LSO)** 

restricted to the high-frequency limb.

**4.2.4 The medial superior olive (MSO)** 

The analysis of age-dependent changes of the gerbil IC (Gleich et al., 2011) revealed a significant shrinkage of the IC cross-sectional area (13%) in old as compared to young gerbils. Although the mean number and cross-sectional areas of GABAergic cells in the IC were slightly smaller in old as compared to young gerbils, the difference between both groups was not significant in the sample of 7 young and 18 old gerbils analysed. The agedependent changes in the GABAergic system of the gerbil IC appeared less pronounced than those previously described in rat (Caspary et al., 1995). This might be explained by differences in the degree of peripheral hearing loss of old rats and gerbils.

### **4.2.6 Variation of age-dependent structural changes between auditory nuclei and potential functional consequences**

The structural changes in the different auditory nuclei discussed above (loss of neurons, shrinkage of neurons and shrinkage of the whole nucleus due to loss of innervation) vary considerably. The effect of age appeared least in DCN and LSO and most for AVCN and MSO. Unfortunately, the functional consequences of the age-dependent structural changes in a specific nucleus on auditory processing are typically not well understood except for MSO and LSO, where it has been shown that they process two distinct aspects of binaural sound analysis: MSO analyses inter-aural time differences while LSO analyses inter-aural level differences (see review in Irvine, 1992), two separate cues that can be used for localisation or lateralisation of a sound source. The limited age-dependent pathology in LSO and the more pronounced pathology of MSO suggest that lateralisation of a sound source in old gerbils should be less affected when based on inter-aural level difference and more affected when based on inter-aural time difference. Unfortunately, behavioural data in gerbils addressing this question are not available. However, Babkoff et al. (2002) showed that for a sample of 78 human subjects aged 21-88 years, tested by the presentation of click trains via head phones, lateralisation based on inter-aural level difference did not change with age while the inter-aural time difference for correct lateralisation increased with age. The correlation of the degree of age-dependent structural changes in LSO and MSO of the gerbil and the effect of age on lateralisation based on inter aural level- and inter aural timedifference in humans is an example for a potential causal relationship of structural and functional age-dependent pathology.
