Degeneration of spiral ganglion (cochlear) neurons is one of the most commonly observed changes in the aging inner ear. In humans and some animal species, neuronal degeneration occurs in the absence of sensory hair cell loss. One factor contributing to neuronal presbyacusis may be changes in the production of trophic molecules derived from sensory hair cells, ganglionic supporting cells or the neurons themselves. Several neurotrophic factors are expressed in the inner ear and members of the neurotrophin gene family are known to be critical for development of cochlear and vestibular neurons. To test the hypothesis that changes in neurotrophins and/or their associated receptors contribute to the age- related loss of neurons, a series of complementary experiments will be conducted using gerbil and human inner ear tissue. Aim 4.1 addresses the temporal and spatial expression of neurotrophins and their associated receptors using the reverse transcription polymerase chain reaction and in situ hybridization. Aim 4.2 evaluates the production of neurotrophin- like proteins using immunohistochemistry, in vitro assays of inner ear tissues and enzyme-linked immunoabsorbant assays. Aim 4.3 examines whether the survival or outgrowth of neuronal processes from young and aging cochlear neurons is influenced by exogenously applied neurotrophins or other inner ear-derived factors. Together, the proposed experiments will offer new sights into the role of neurotrophins in the aging inner ear as well as information regarding the therapeutic potential of neurotrophic molecules in preventing age-related hearing loss.