LACK OF NEUROTROPHIN-3 CAUSES LOSSES OF BOTH CLASSES OF SPIRAL GANGLION NEURONS IN THE COCHLEA IN REGION-SPECIFIC FASHION

Essential functions of neurotrophin 3 (NT-3) in regulating afferent an d efferent innervation of the cochlea have been characterized by compa rison of normal and NT-3 mutant mice. NT-3 deficiency has striking, re gion-specific effects, with complete loss of sensory neurons in the ba sal turn and dramatic but incomplete neuronal loss in the middle and a pical turns, The sensory innervation of inner and outer hair cells was reorganized in mutant animals. Instead of a strictly radial pattern o f innervation, the axons of remaining sensory neurons projected spiral ly along the row of inner hair cells to innervate even the most basal inner hair cells, Innervation of outer hair cells was strongly reduced overall and was not detected in the basal turn. The presence of fiber s extending to both inner and outer hair cells suggests that subsets o f types I and II sensory neurons survive in the absence of NT-3. Likew ise, projections of the cochlea to auditory nuclei of the brainstem we re attenuated but otherwise present. Equally striking changes in effer ent innervation were observed in mutant animals that closely mimicked the abnormal sensory innervation pattern, Despite these impressive inn ervation deficiencies, the morphology of the organ of Corti and the de velopment of inner and outer hair cells appeared comparatively normal.