DEGENERATION OF VESTIBULAR NEURONS IN LATE EMBRYOGENESIS OF BOTH HETEROZYGOUS AND HOMOZYGOUS BDNF NULL MUTANT MICE

The generation of mice lacking specific neurotrophins permits evaluati on of the trophic requirements of particular neuronal populations thro ughout development. In the present study, we examined the developing v estibulocochlear system to determine the time course of neurotrophin d ependence and to determine whether competition occurred among developi ng cochlear or vestibular neurons for available amounts of either brai n-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/5), Bot h cochlear and vestibular neurons were present in mice lacking NT-4/5, In contrast, vestibular neurons decreased in number beginning at mid- stages of inner ear development, in mice lacking BDNF. Early in develo pment (E12.5-13), the size of the vestibular ganglion was normal in bd nf(-/-) mice. Decreased innervation to vestibular sensory epithelia wa s detected at E13.5-15, when progressive loss of all afferent innervat ion to the semicircular canals and reduced innervation to the utricle and saccule were observed, At E16.5-17, there was a reduction in the n umber of vestibular neurons in bdnf(-/-) mice. A further decrease in v estibular neurons was observed at P1 and P15, Compared to bdnf(-/-) mi ce, mice heterozygous for the BDNF null mutation (bdnf(+/-)) showed an intermediate decrease in the number of vestibular neurons from E16.5- P15. These data indicate a late developmental requirement of vestibula r neurons for BDNF and suggest competition among these neurons for lim ited supplies of this factor.