The proper development of auditory function requires a complex interaction of nerve cells within the central nervous system with sensory cells of the peripheral organ. The cochlea is the peripheral sensory organ in the inner ear which perceives mechanical vibratory impulses that are transferred as sound stimuli by cochlear neurons, the spiral ganglion cells. The auditory impulses reach the brainstem of the central nervous system via afferent fibers of the auditory nerve. The brain stem in turn sends the efferent innervation to the organ of Corti to provide the fine sound discrimination and to lower the noise background. It is believed that efferent innervation modulates the sensitivity of the sensory cells to sound by releasing the chemical, acetylcholine. Little is known about the development of these cholinergic (acetylcholine-releasing) efferents or their molecular properties. The P.I.s' research concerns the development of the enzymes choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) and its molecular forms, which respectively synthesize and breakdown acetylcholine. Their data suggest that in the mouse the cholinergic efferents are present throughout the organ of Corti at birth. Postnatal increases in the levels of AChE molecular forms correspond to the time of innervation of inner and outer hair cells. We propose to use biochemical, histochemical and immunochemical techniques to study the amount and distribution of cholinergic enzymes in the efferent fibers along the spiral and radial axes of the developing organ. The goal of this work is to determine the effect the normal developmental time course for the cholinergic innervation of the hair cells has on the expression of synaptic and non-synaptic AChE molecular forms. The research will determine the time when cholinergic efferents establish contacts with their targets, the morpological and molecular nature of these efferents along the cochlea, and indicate the cellular interactions necessary for morphological and molecular synaptic differentiation to occur. The research will help identify the causes and consequences of normal and abnormal auditory development.
