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Firing Properties of Spiral Ganglion Neurons: Functional Contribution of Hyper-Polarization-Activated, Cyclic Nucleotide-Gated Channels in Primary Auditory Neurons of the Mouse Inner Ear

Kim, Ye Hyun
Format
Thesis/Dissertation; Online
Author
Kim, Ye Hyun
Advisor
Holt, Jeffrey
Abstract
The hyperpolarization-activated current, Ih, is carried by members of the Hcn channel family and contributes to resting potential and firing properties in excitable cells of various systems, including the auditory system. Ih has been identified in spiral ganglion neurons (SGNs), however, its molecular correlates and their functional relevance have not been established. To examine the molecular composition of the channels that carry Ih in SGNs, we examined Hcn mRNA harvested from spiral ganglia of wild-type (WT) neonatal and adult mice using quantitative RT-PCR. We show expression of Hcn1, 2, and 4 subunits in SGNs, with Hcn1 being the most highly expressed at both stages. To determine the physiological expression of HCN subunits in SGN cell bodies, we used the whole-cell, tight-seal technique in voltage-clamp mode to record Ih from WT SGNs and those deficient in Hcn1, Hcn2 or both. We found that HCN1 is a major functional subunit contributing to Ih in SGNs. Deletion of Hcn1 resulted in significantly reduced conductance, slower activation kinetics, and hyperpolarized half-activation potentials. To investigate the contribution of Ih to SGN function, we recorded membrane responses in current-clamp mode. We demonstrate that Ih contributes to depolarized resting potentials, sag and rebound potentials, accelerates rebound spikes following hyperpolarization, and minimizes spike jitter for small depolarizing stimuli. Auditory brainstem responses of Hcn1-deficient mice showed longer latencies, suggesting that HCN1-mediated Ih is critical for synchronized action potential firing in SGNs. Together, our data indicate Ih contributes to SGN membrane properties and plays a role in temporal aspects of signal transmission between the cochlea and the brain, which are critical for normal auditory function. To further investigate how temporal auditory signal processing is achieved between SGNs and Inner hair cells (IHCs), we have developed a new intact preparation and recording paradigm, where mechanotransduction of the IHCs and recording of SGN responses are possible in simultaneous fashion. We demonstrate, for the first time, that SGNs are capable of transmitting signals in response to mechanical stimulation of IHC hair bundles as early as postnatal day one, at the base of the cochlea. In addition to processing mechanically driven IHC stimuli, we show that early postnatal SGNs fire spontaneous action potential in a position-dependent manner, similar to spontaneous Ca2+ spike patterns seen in immature IHCs before the onset of hearing.
Language
English
Published
University of Virginia, Department of Neuroscience, PHD (Doctor of Philosophy), 2014
Published Date
2014-04-30
Degree
PHD (Doctor of Philosophy)
Collection
Libra ETD Repository
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