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 new level 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 to evaluating 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.

Public Health Relevance

Loss of hearing is a devastating sensory disorder that affects millions of Americans, but effective therapies to treat this communication impairment are still being developed. While existing technologies such as the cochlear implant are effective, and novel approaches, such as neurotrophin infusion and neuron replacement therapies, are promising, there is much that needs to be learned to bring these approaches to their full potential. By studying the neurons that are the targets of these approaches, our studies provide the foundation necessary to move all of these therapeutic innovations one step closer to the clinic.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001856-24
Application #
9380327
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1992-12-01
Project End
2019-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
24
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Rutgers University
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
001912864
City
Piscataway
State
NJ
Country
United States
Zip Code
Smith, Felicia L; Davis, Robin L (2016) Organ of Corti explants direct tonotopically graded morphology of spiral ganglion neurons in vitro. J Comp Neurol 524:2182-207
Nishimura, K; Weichert, R M; Liu, W et al. (2014) Generation of induced neurons by direct reprogramming in the mammalian cochlea. Neuroscience 275:125-35
Crozier, Robert A; Davis, Robin L (2014) Unmasking of spiral ganglion neuron firing dynamics by membrane potential and neurotrophin-3. J Neurosci 34:9688-702
Liu, Wenke; Davis, Robin L (2014) Calretinin and calbindin distribution patterns specify subpopulations of type I and type II spiral ganglion neurons in postnatal murine cochlea. J Comp Neurol 522:2299-318
Liu, Q; Lee, E; Davis, R L (2014) Heterogeneous intrinsic excitability of murine spiral ganglion neurons is determined by Kv1 and HCN channels. Neuroscience 257:96-110
Liu, Qing; Manis, Paul B; Davis, Robin L (2014) I h and HCN channels in murine spiral ganglion neurons: tonotopic variation, local heterogeneity, and kinetic model. J Assoc Res Otolaryngol 15:585-99
Green, Steven H; Bailey, Erin; Wang, Qiong et al. (2012) The Trk A, B, C's of neurotrophins in the cochlea. Anat Rec (Hoboken) 295:1877-95
Flores-Otero, Jacqueline; Davis, Robin L (2011) Synaptic proteins are tonotopically graded in postnatal and adult type I and type II spiral ganglion neurons. J Comp Neurol 519:1455-75
Chen, Wei Chun; Xue, Hui Zhong; Hsu, Yun Lucy et al. (2011) Complex distribution patterns of voltage-gated calcium channel ?-subunits in the spiral ganglion. Hear Res 278:52-68
Davis, Robin L; Liu, Qing (2011) Complex primary afferents: What the distribution of electrophysiologically-relevant phenotypes within the spiral ganglion tells us about peripheral neural coding. Hear Res 276:34-43

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