Organization and regulation of neuronal intrinsic properties in the spiral ganglion

My dissertation projects were carried out to explore the functional significance of the first auditory neural element, the spiral ganglion neurons, in coding sound information. Through patch clamp recording and immunocytochemical approaches two distinct organizational patterns of neuronal firing properties were identified in a preparation that retains neuronal relative position in vitro. The first is a gradient of timing-related features that corresponds well with the tonotopic map across the cochlea. The second is non-monotonically distributed threshold levels that show the greatest sensitivity in the middle cochlea, thus overlapping with the range of best hearing. These findings suggest neuronal intrinsic membrane properties could potentially contribute to encoding distinct auditory features related to modalities such as frequency and intensity. We further investigated how diversified intrinsic excitability may help form neuronal population code with firing rate changes to represent different sound levels. Inner hair cells send discrete auditory signals to 20-25 auditory nerve fibers, each forming one synapse on a single receptor. Although these fibers convey identical frequency information, they display diverse thresholds and spontaneous rates. This is important because it extends the coding range of the neuronal population by shifting their rate level functions. Moreover, nerve fibers in the mid-cochlear display specialized sensitivity (Taberner and Liberman, 2005), which overlaps with animals’ best frequency range. We found intrinsic voltage thresholds were heterogeneous in each region, which, interestingly, are also most sensitive in the mid-cochlea. Characterization of neuronal resting potential revealed the enhanced mid-cochlea sensitivity might be contributed by dual parameters of intrinsic excitability that the most sensitive sub-threshold ranges were achievable with subtractive effects of decreased threshold and elevated resting potential in the middle ganglion. The pharmacological studies demonstrated α-dendrotoxin sensitive, shaker-related potassium channels could non-monotonically regulate neuronal threshold and resting potential, whereas Ih current contributes predominantly to resting potential regulation. The investigation of spiral ganglion neuron intrinsic excitability based on resting potential and voltage threshold measurements suggests that in addition to middle ear mechanics and synaptic mechanisms the neurons themselves are relevant to the auditory nerve fibers in vivo responses to different sound levels.Ph.D.Includes bibliographical referencesIncludes vitaby Qing Li