Our interest is in understanding the molecular substrates that promote the maintenance and survival vestibular and cochlear ganglion neurons in the normal adult mammal. The erbB family of receptor tyrosine kinases (RTKs) play a role in neuron and glial cell function in the nervous system and may be involved in the normal growth and maintenance of the afferent and efferent innervation in the mammalian inner ear. We have begun to analyze expression patterns of erbB subfamily RTKs in the postnatal rat auditory and vestibular periphery. All of the erbB subfamily RTKs were detected in the cell bodies of adult vestibular ganglion neurons (VGN) in situ and in the cell bodies and neurites of cultured postnatal day 5 (P5) rat VGN. Preliminary studies indicate that activation of erbB family signaling is involved in the survival of postnatal VGN. An antibody that blocks erbB2-mediated signaling was found to inhibit VGN viability in survival assays suggesting that erbB family signaling plays an active role in maintaining VGN viability. In this application, these phenomena will be evaluated in more detail in the VGN culture system and will begin to be analyzed in the cochlear ganglion neuron context. These studies may provide insight into molecular mechanisms through which vestibular and cochlear ganglion neuron viability in the degenerating (aging) and in the damaged/regenerating mammalian inner ear may be facilitated.
