THE ROLE OF NEUROTROPHIC FACTORS IN REGULATING THE DEVELOPMENT OF INNER-EAR INNERVATION

Several neurotrophins and their receptors regulate the survival of ves tibular and cochlear neurons and probably also the efferent and autono mic neurons that innervate the inner ear. Mice lacking either brain-de rived neurotrophic factor (BDNF) or its associated receptor, TrkB, los e all innervation to the semicircular canals and have reduced innervat ion of the outer hair cells in the apical and middle turns of the coch lea. Mice lacking neurotrophin-3 (NT-3) or its receptor, TrkC, lose ma ny spiral ganglion cells predominantly in the basal turn of the cochle a. Nerve fibers from spiral ganglion cells in the middle turn extend t o inner hair cells of the base. In mice lacking both BDNF and NT-3, or both TrkB and TrkC, there is a complete loss of innervation to the in ner ear. Thus, these two neurotrophins and their associated receptors have been shown to be absolutely necessary for the normal development of afferent innervation of the inner ear. Current research efforts are testing the therapeutic potential for neurotrophins to treat hearing loss.