CELLULAR PROCESSES OF CENTRAL AUDITORY NEURONAL DEATH

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DESCRIPTION: (Adapted from the Investigator's Abstract) Damage to the inner ear can occur from a variety of causes, including diseases, noise and ototoxic drugs. Prolonged damage to the cochlea can have lasting and often detrimental effects on auditory neurons in the CNS because these neurons rely on continuous afferent input for normal function. Interactions between the periphery; and the CNS have been studied extensively in the avian auditory system. Auditory neurons in the cochlear nucleus (n. magnocellularis, NM) receive their only excitatory input from the cochlea via the eighth nerve. Destruction of the cochlea in hatchling chickens sets in motion a series of rapid metabolic changes in postsynaptic NM neurons, including upregulation of oxidative function. Within several days, 30% of NM neurons will die and the remainder show long-lasting decreases in metabolic activity. When the cochlea is damaged in an adult chicken, the extent of the response in NM varies with the breed of animal. In mammals damage to the cochlea is permanent. However, birds have the remarkable capacity to replace damaged cochlear hair cells. Repair begins within several days of damage, and anatomical recovery s followed by the return of substantial auditory function. Although the mechanisms of cochlear recovery have been examined extensively, much less is known about how the CNS responds to hair cells loss and regeneration. In hatchling birds we will examine how NM neurons respond to reversible loss of cochlear function caused by gentamicin. We will evaluate how the number of NM neurons changes following gentamicin damage to the cochlea, and determine whether a reversible oxidative upregulation occurs. We will determine whether new neurons are generated in NM similar to the replacement of cochlear hair cells. In adult birds we will test the hypothesis that differences in cochlear function underlie the different CNS responses to cochlear ablation in birds of different breeds. We will evaluate whether adult birds differ in their response to environmental noise, and whether CNS responses can be predicted by cochlear integrity. Finally, we will evaluate the capacity for hair cell regeneration in adult birds. Our ability to repair damage to the cochlea is continuously improving, with advances in cochlear implant technology and the possibility for regeneration of mammalian cochlear hair cells. These advances in peripheral repair make it all the more crucial to assess the functional capacity of the auditory CNS.