Results now show a diversity in amino acid transmitters and receptor subunits that provide for the specialized shaping of neuronal responses and that their changes can underlie auditory brain stem plasticity. Our first Specific Aim is based on our finding decreased GABA release and correlated decreased inhibition in the inferior colliculus (IC) 3 weeks following deafness. It uses immunocytochemistry and tract tracing to test the hypotheses that decreased GABA release is a consequence of decreased GABA in terminals, with a specific GABA sub-circuit to the IC effected, rather than a """"""""global"""""""" decrease in all inputs. Caspary's group found GABA-A receptor subunit changes that correlated with age-related hearing loss, but couldn't differentiate """"""""pure aging"""""""" versus """"""""deafness"""""""". Our second specific aim uses quantitative in situ hybridization to test if there will be comparable subunit changes in our more """"""""pure deafness"""""""" model, as well as changes in glycine receptor subunits in the DCN where a glycine mediated decrease in inhibition is found. We further hypothesize correlation between changes in transmitter and receptor. We predict GABA but not glycine receptor subunit changes in the CIC and glycine but not GABA receptor subunit changes in fusiform cells. Studies will also uses receptor autoradiography to test a functional correlate, ligand binding. Our final specific aim uses gene micro arrays to screen for differential expression following deafness and test the hypothesis that deafness induces decreased expression of presynaptic neurotransmitter- related genes and compensatory expression of post-synaptic genes. It then uses quantitative in situ hybridization to test the hypothesis that changes will be specific to distinct neuron types. These studies will provide new information on the role of transmitters and receptors in central auditory plasticity. This will, in turn, increase our understanding of the molecular basis of central auditory system dysfunction and provide clues for interventions that might help improve the re-introduction of hearing following deafness, currently with cochlear prostheses and in the future after hair cell regeneration.
