Age-related hearing loss (presbycusis) is the major communication disorder of industrialized society and is second only to arthritic diseases in its impact on the quality of life for people over 65. Disproportionately poor speech discrimination, particularly in the presence of background noise is one characteristic of age-related hearing loss and is thought to reflect, in part, changes in the central auditory system. The inferior colliculus (IC) is comprised of three major subdivisions, the dorsal cortex, the external cortex, and the external cortex, and the central nucleus, and is a critical auditory midbrain processing center for both ascending and descending auditory pathways. Neurons in the IC perform spatial and temporal coding of complex signals, sound localization, and are probably involved in the extraction of acoustic signals embedded in noise. The neurotransmitter gamma-aminobutyric acid (GABA), along with glycine and the excitant amino acids (EAAs) have been shown to be essential for coding many of these important auditory tasks in the IC. Recently, a number of neurochemical and immunocytochemical studies, as well as the preliminary studies for this grant suggest an age-related decline in GABA-mediated inhibition, alterations in the levels of EAA receptors, and loss of """"""""excitatory-type"""""""" presynaptic terminals similar to those that use an EAA neurotransmitter. A significant but smaller loss of glycine has also been reported. These losses or imbalances are likely to impair IC function, degrading the ability to detect signals in noise and localize sounds. The objective of the present study is to further define age-related changes in the synaptic organization underlying inhibitory and excitatory coding in two different frequency areas in the IC. Age-related synaptic changes will also be assessed in the cochlear nucleus (CN) and compared to those described in the IC, the principal target of its projections. For each IC and CN subdivision, pre- and postsynaptic age-related changes will be examined using quantitative immunogold electron microscopy, quantitative receptor autoradiography and in situ hybridization to address the following questions; 1) Are there age-related reductions of GABA- and/or glycine- immunoreactive terminals? 2) Are there age-related changes in the number of GABA and glycine terminals contacting specific neuronal areas (i.e., somata and dendrites of various calibers) that would reflect a corresponding change in the distribution of GABAergic synaptic input? 3) Are there similar changes with """"""""excitatory type"""""""" terminals"""""""" 4) Are there age-related changes in the morphology of the three terminal types? 5) Are age-related changes in number and distribution of GABA, glycine, and EAA receptors? 6) Are there age-related changes in the patterns of GABAA and glutamate receptor subunit expression? Knowledge of the pre-and postsynaptic substrates of age-related changes in inhibition and excitation in the IC and CN will enhance our understanding of central presbycusis and will allow us to subsequently explore the mechanisms underlying these changes in an effort to achieve our long range goal to develop pharmacotherapies for certain types of ag e-related communicative disorders.
