[F31] Molecular Mechanisms of Ribbon Synapse Formation in the Inner Ear
Ente: National Institute on Deafness and Other Communication Disorders
Scadenza: 2027-11-29
Importo max: 50.114 EUR
Paese: US
Descrizione
PROJECT SUMMARY
Type I spiral ganglion neurons (SGNs) are the sensory afferents of the inner ear that form ribbon synapses with
mechanosensory inner hair cells (IHCs). Each IHC is mono-synaptically innervated by up to 30 SGNs with ribbon
synapses on single IHCs forming highly stereotyped gradients of varying properties that correlate with the
position of these synapses along the basolateral surface of the cell. The mechanisms that regulate the formation
of synapses with different properties and localizations along the basolateral axis of single IHCs are not known.
Taking advantage of recent single cell RNA sequencing data sets generated by us and others, I am now able to
rigorously test the molecular mechanisms guiding the development, refinement, and function of IHC ribbon
synapses. Based on recent studies and my preliminary data, neurexin 3 (NRXN3) stands out as a potential
regulator of synapse formation between IHCs and SGNs. In this study I propose to investigate NRXN3 as a
potential contributor to IHC-SGN synapse formation using mutant mouse models conditionally lacking Nrxn3 with
established assays of in situ hybridization, immunostaining, electrophysiology, electron microscopy, and auditory
brainstem recordings. I anticipate that loss or mutation of NRXN3 contributes to the molecular pathogenesis of
hearing deficits in humans.
Istituzione: JOHNS HOPKINS UNIVERSITY
PI: Blake Creighton
Progetto: 5F31DC022167-02
Settori: National Institute on Deafness and Other Communication Disorders
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