Molecular Basis of a Critical Period in Cochlear Nucleus

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DESCRIPTION (provided by applicant): The goal of the present study is to identify the molecular mechanisms that could define a period of dramatic susceptibility to loss of peripheral input in the mouse brainstem cochlear nucleus (CN). The basis of this period and the switch during development to CN neuron survival independent of input is essentially unknown. These studies will use microarrays to identify candidate genes that change in level of expression during and after this critical period as well as to identify genes that are transcriptionally regulated (induced or repressed) following removal of input by cochlear ablation. Genetically altered mice, possibly in combination with other gene manipulation technologies, will be used to study the functional roles of selected candidate genes in death and survival of CN neurons following cochlear ablation. These studies will also examine the role of 8th nerve activity in promoting survival of CN neurons during the critical period, a time before the onset of hearing in mice. With recent advances in cochlear implant technologies, it is of great importance to understand the effects of sensory deprivation and the return of stimulation on central auditory neurons both during development and in adulthood in order to improve rehabilitation of auditory function.