The development of hearing has been studied in several experimental animals and in humans. As a result, some of the morphological and physiological changes associated with the onset of auditory function have been defined, but little is known about the specific cellular and molecular events mediating this process. Such information is essential to understanding the molecular basis of normal hearing and the changes leading to hearing losses. The objective of the proposed research is to determine the contribution of certain enzymes and other regulatory and structural proteins and glycoproteins to the function of the highly specialized cells and membranes in the cochlea. This will be accomplished by applying specific histochemical methods to systematically trace their expression during the onset and maturation of hearing in neonatal animals. The research approach will be comprehensive. Microelectrode measurements of cochlear potentials and measures of whole nerve action potentials will be correlated with morphological and histochemical findings from the same ear. The research will focus on regions of the cochlea which have received little attention in developmental and functional studies. Experiments using ion-sensitive microelectrodes are planned to test the hypothesis that recently defined cell populations rich in either Na+, K+-ATPase or carbonic anhydrase are involved in generating and maintaining cochlear ion gradients and electrical potentials. This comprehensive and systematic study of the developing cochlea will contribute significantly to our understanding of the molecular and cellular events leading to the establishment of normal auditory function.