Morphological and neurochemical correlates of vestibular compensation

Morphometric analysis of the cat's superior vestibulo-ocular neurons (SVON) 8 weeks, and 1 and 2 years following vestibular neurectomy or labyrinthectomy revealed similar changes which indicate that an excitatory mode of input to the denervated SVON is responsible for the behavioral recovery. These changes include an increased proportion of strong asymmetric synapses, somal spines surrounding the SP, increased size of and number of SP at long (> 1 year) survival periods. There is a parallel decrease < 1 year and increase > 1 year of contralateral vestibular nerve SP on SVON which matches in timing and magnitude the number of ipsilateral vestibular nerve SP after surgical ablation. These unexpected SVON are consistent with the hypothesis that neurotrophins regulate symmetry in the adult vestibular system. This hypothesis was tested in a series of 13 heterozygous brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) knockout mice. Following unilateral surgical labyrinthectomy the BDNF and NT4 knockout mice demonstrated no delay in behavioral recovery compared to their normal littermate controls. However, the NT3 knockout mice required twice the time to recover from balance deficits as their littermate controls. These results indicate that NT3 protein is important for normal vestibular function.