[Truncated abstract] The cochlea presumably possesses a number of regulatory mechanisms to maintain cochlear sensitivity in the face of disturbances to its function. Evidence for such mechanisms can be found in the time-course of the recovery of CAP thresholds during experimental manipulations, and in observations of slow oscillations in cochlear micromechanics following exposure to low-frequency tones (the “bounce phenomenon”) and other perturbations. To increase our understanding of these oscillatory processes within the cochlea, and OHCs in particular, investigations into cochlear regulation were carried out using a combination of mathematical modelling of the ionic and mechanical interactions likely to exist within the OHCs, and electrophysiological experiments conducted in guinea pigs. The electrophysiological experiments consisted of electrocochleographic recordings and, in some cases, measurement of otoacoustic emissions, during a variety of experimental perturbations, including the application of force to the cochlear wall, exposure to very-low-frequency tones, injection of direct current into scala tympani, and intracochlear perfusions of artificial perilymph containing altered concentrations of potassium, sodium, and sucrose. To obtain a panoramic view of cochlear regulation under these conditions, software was written to enable the interleaved and near-simultaneous measurement of multiple indicators of cochlear function, including the compound action potential (CAP) threshold, amplitude and waveshape at multiple frequencies, the OHC transfer curves derived from low-frequency cochlear microphonic (CM) waveforms, distortion-product otoacoustic emissions (DPOAEs), the spectrum of the round-window neural noise (SNN), and the endocochlear potential (EP). ... The mathematical model we have developed provided a physiologically-plausible and internally-consistent explanation for the time-courses of the cochlear changes observed during a number of different perturbations. We show that much of the oscillatory behaviour within the cochlea is consistent with underlying oscillations in cytosolic calcium concentration. We conclude that a number of the discrepancies between the simulation results and the experimental data can be resolved if the cytosolic calcium functions as two distinct pools: one which controls basolateral permeability and one which controls slow motility. This two-calcium-pool model is discussed.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2005|