Supporting Cells Regulate Synapse Formation in the Vestibular Epithelium

GÓMEZ-CASATI, ME; MURTIE J; RIO C; STANKOVIC, K; LIBERMAN MC; CORFAS G

Baltimore, MD, USA

Congreso; The Association for Research in Otolaryngology, midwinter meeting; 2009

Supporting cells of the vestibular epithelium are closely associated with hair cells and afferent nerve terminals, making them potential contributors to vestibular development and function, but this remains to be shown. Vestibular supporting cells express erbB receptors and sensory neurons express the erbB ligand neuregulin 1. We tested the potential roles of this pathway in the vestibular system using a transgenic mouse line in which erbB receptor signaling in vestibular supporting cells is blocked by expression of a dominant-negative erbB receptor (DN-erbB4). Adult DN-erbB4 mice display behaviors consistent with vestibular dysfunction (ataxia, spinning behavior, inability to swim). Evoked potential recordings showed that vestibular function is severely affected by P21, even though macular epithelia are normal in size and general structure. FM1-43 dye uptake and neurofilament staining are normal in mutant mice, indicating that hair cell mechano-transduction and afferent innervation are unaffected. In contrast, synaptic site numbers (defined as the colocalization of RIBEYE and GluR23 staining) are dramatically reduced, suggesting a synaptic defect. Analysis of synapse numbers at different postnatal ages showed that the number of synaptic puncta increases by 5 fold between birth and P21 in wild types, but this does not occur in the mutants. Molecular analysis showed that the synaptic alterations are accompanied by a dramatic reduction in BDNF and we found that over-expression of BDNF in vestibular supporting cells after birth using tamoxifen-induced transgene activation rescues the functional and anatomical phenotypes of DN-erbB4 mice. Together these results indicate that vestibular supporting cells contribute to the formation maturation of synapses in the postnatal vestibular maculae and that this is mediated by NRG1-erbB and BDNF-TrkB signaling.