Once thought to be relatively uniform, neurons of the spiral ganglion are now known to possess diverse electrophysiological phenotypes and ion channel composition. Importantly, these neuronal firing features are not distributed at random, but vary systematically along the frequency axis of the cochlea. Properties related to action potential timing and number, such as latency, duration, and accommodation, are distinctly different in apical and basal neurons. Conversely, properties that affect cell responsiveness, such as threshold level, vary locally within each frequency range. These novel findings were made more intriguing by the observation that firing patterns and the underlying ion channel density were regulated by two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). BDNF causes spiral ganglion neurons to fire with short latencies, abbreviated action potential durations, and rapid accommodation. NT-3, on the other hand, had the opposite effect. These results highlight the exquisite complexity of a seemingly simple collection of peripheral neurons, and have profound implications for therapeutic approaches being developed in the cochlear implant field. For example, should neurotrophins be used to enhance neuronal survival, our studies suggest that care must be taken with their administration in order to maintain neuronal firing patterns that are appropriate for a particular frequency region. However, before such conclusions can be drawn critical issues must be resolved. Firstly, it is imperative to understand the significance of the complex firing patterns that we have observed and place them in the appropriate functional context. Secondly, the precise combinations of voltage-dependent ion channels that regulate the electrophysiological features must be defined. Finally, regulation of physiological properties by extrinsic factors will be characterized fully in order to appreciate their role in establishing the firing patterns of postnatal spiral ganglion neurons. The combination of electrophysiological and immunocytochemical approaches proposed in the current application will provide new insights into the remarkable complexity of spiral ganglion neurons, cells that may hold the key to remediation of hearing loss following disease or injury.
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