Spiral ganglion neurons transmit signals from peripheral receptors to central targets, thus serving as the gateway to the brain. While much is known regarding their responses to sound, we are just beginning to fully appreciate their sophisticated neurobiological and cell biological properties. By studying spiral ganglion neurons isolated from their synaptic targets in vitro, we discovered that their electrophysiological signature is associated with specific tonotopic specializations and is precisely regulated by neurotrophins, two key features that need to be reproduced when developing treatments to restore hearing. Our recent findings, however, show that there is more to be learned. Our first goal is to understand the contribution of voltage-gated calcium channels, which participate both electrically and chemically in their roles as modulators of action potential waveform, intracellula signaling, and transmitter release. Secondly, by opening a window through the myelin to examine the neuronal membrane properties in acute preparations, we expand our view to a system in which hair cell innervation is retained. And finally, we take our investigation to a newlevel by elucidating mechanisms that influence axonal outgrowth and soma size. In our unique co-culture system we observe de novo regeneration of axon domains expressing distinct PNS-like or CNS-like characteristics separated by a transition zone. Thus, rather than being limited toevaluating overall neurite outgrowth, we now have the ability to assess regulators of the tonotopically-relevant PNS/CNS axon ratio established under controlled conditions. Thus, we are poised to enrich our understanding of the properties of spiral ganglion neurons, which is needed for cells that may hold the key to remediation of hearing loss following disease or injury. It is clear that only with an accurate understanding of these elegantly-designed neurons, can approaches such as neurotrophin-enhanced cochlear implant technologies and cell replacement therapies be truly successful.
|Effective start/end date||12/1/92 → 11/30/19|
- National Institutes of Health (NIH)