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Volume 17, Number 16, Issue of August 15, 1997 pp. 6213-6225
Copyright ©1997 Society for Neuroscience

Lack of Neurotrophin 3 Causes Losses of Both Classes of Spiral Ganglion Neurons in the Cochlea in a Region-Specific Fashion

Received Jan. 13, 1997; revised May 29, 1997; accepted June 3, 1997.

Bernd Fritzsch¹, Isabel Fariñas², and Louis F. Reichardt²

¹ Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, and ² Program in Neuroscience, Department of Physiology and Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0724

Essential functions of neurotrophin 3 (NT-3) in regulating afferent and efferent innervation of the cochlea have been characterized by comparison of normal and NT-3 mutant mice. NT-3 deficiency has striking, region-specific effects, with complete loss of sensory neurons in the basal turn and dramatic but incomplete neuronal loss in the middle and apical turns. The sensory innervation of inner and outer hair cells was reorganized in mutant animals. Instead of a strictly radial pattern of innervation, the axons of remaining sensory neurons projected spirally 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 fibers extending to both inner and outer hair cells suggests that subsets of types I and II sensory neurons survive in the absence of NT-3. Likewise, projections of the cochlea to auditory nuclei of the brainstem were attenuated but otherwise present. Equally striking changes in efferent innervation were observed in mutant animals that closely mimicked the abnormal sensory innervation pattern. Despite these impressive innervation deficiencies, the morphology of the organ of Corti and the development of inner and outer hair cells appeared comparatively normal.

Key words: NT-3 mutants; inner ear; cochlea; spiral ganglion; innervation; ear development

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