The goal of this developmental project is to investigate how auditory neurons in the cochlear nucleus acquire their unique physiological properties. Clarification of how the diverse physiological responses observed in the adult CN are established will improve our understanding of the development of hearing, and increase our knowledge of auditory system function. As in other brain regions, neuronal activity in CN is partially determined by the nature of the K+ channels present in the cell membrane. In the proposed experiments the differentiation of CN neurons will be studied by investigating K+ channel expression in postnatal mice. There are three objectives. The first is to identify age-dependent changes in the biophysical properties of acutely isolated CN neurons. These experiments test the hypothesis that CN neurons differentiate from a homogenous population to one made up of dissimilar elements, and that these developmental changes are due in part, to alterations in the present and/or properties of K+ channels. The second goal is to assess the specificity of K+ channel expression among CN neurons and to determine the time course for acquisition of mature K+ channel complements through the use of in situ hybridization. This will test the hypothesis that there are age-dependent changes in the types of K+ channel mRNAs expressed among CN neurons.
The third aim i s to correlate the membrane properties of physiologically identified CN neurons with the expression of specific K+ channel mRNAs by combining whole-cell recording with polymerase chan reaction. These experiments will directly test the hypothesis that the physiological profiles is associated with the particular complement of K+ channels and provide information regarding mechanisms responsible for the development of response properties of CN neurons. These data will assist in the evolution of improved models of information processing in CN, and increase our knowledge of neuronal differentiation. Indentification of the mechanisms used by the brainto process acoustic signals is a necessary step in the progress toward rational treatments for conditions where the auditory system is malfunctioning due to genetic disorder, disease, or trauma.
