Our studies have revealed that the spiral ganglion is more than just a collection of axon-like elements that act merely as a simple relay into the central nervous system. Instead, we and others have found that this relatively homogeneous group of neurons possesses a rich complexity that is only now beginning to be understood. In fact, the powerful regulation of spiral ganglion neurons by neurotrophins, in combination with their precise and frequency-specific organization, makes this an exemplary model system to study the molecular and cellular foundations that regulate the initial stages of parallel processing and sensory encoding. Not only do these neurons have a prominent functional role, they are also the targets of therapeutic remediation with cochlear implant technology. Understanding their endogenous firing properties and membrane characteristics will undoubtedly be helpful in tailoring electrical input for optimal stimulation. Furthermore, our studies suggest that should neurotrophins be used clinically to enhance neuronal survival, care must be taken with their administration in order to maintain firing patterns and thresholds that are appropriate for the particular frequency region of innervation. However, before such conclusions can be drawn, critical issues must first be resolved. It is important to understand the basic foundation upon which this organization is actually constructed, determine precisely how exogenously-applied neurotrophin regulation occurs, and examine whether the effects of neurotrophins can be reproduced by manipulation of hair cell-neuronal contact. With the push to move cochlear-infused neurotrophins into clinical trials, it is imperative now more than ever to examine the biophysical impact of neurotrophins on the spiral ganglion in model systems. The use of electrophysiological, molecular, and immunocytochemical methods combined with innovative tissue culture systems will provide new insights into the precise organization of spiral ganglion neurons, cells that may hold the key to remediation of hearing loss following disease or injury.

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. Although the hearing sciences have been on the forefront of delivering an ?artificial ear? or cochlear implant, there is much that needs to be learned to bring this device to its potential. Our studies provide the basic scientific foundation necessary to move the existing therapeutic innovations forward. By studying the neurons that are the targets of the cochlear implant, the precise signals that must be conveyed into the brain are being identified and the mechanisms critical for neuronal survival and specification are being revealed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
3R01DC001856-17S1
Application #
7844599
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2009-06-01
Project End
2009-10-31
Budget Start
2009-06-01
Budget End
2009-10-31
Support Year
17
Fiscal Year
2009
Total Cost
$13,905
Indirect Cost
Name
Rutgers University
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
001912864
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
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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