One of the major challenges in auditory neuroscience is to elucidate the elementary events that underlie sensory transduction and the initial stages of neuronal encoding. My research program addresses this issue by focusing on spiral ganglion neuronal signaling. We utilize patch clamp electrophysiology and immunocytochemistry to characterize neural encoding and to evaluate the effects of neurotrophins on the distribution of voltage-gated ion channels.
The goal of this project is to determine how diverse groups of ion channels observed within the VIIIth cranial nerve regulate auditory signal processing. Our patch-clamp studies have shown that primary-auditory neurons possess potassium (K+) channels within the internodal membrane that are capable of rhythmically altering the membrane potential and responding to extra-synaptic modulation. The functional significance of this finding impacts not only on our knowledge of how peripheral myelinated neurons modify neuronal activity but also opens up the interesting possibility that these channels are regulated through second messenger systems to mediate long-term effects. The full implication of how K+ channel modulation contributes to coding in the auditory periphery is at the frontier of our scientific understanding of how sound is coded in the nervous system.
To evaluate the mechanisms that regulate tissue formation in the peripheral auditory system, we are concentrating our efforts exclusively on the role of cell-substratum events. We recently made the fortuitous observation that by culturing explants of the mouse neonatal stria vascularis, the process of tissue formation could be observed dynamically in vitro. These studies were possible because all three cell types that compose the tissue were recognizable, allowing observation of these identified cells in live cultures. We are evaluating the function of three molecules: Laminin, fibronectin and osteopontin and have found that they are distributed in temporally and spatially specific patterns and have characteristic effects upon being blocked with affinity-purified antibodies. This culture system represents a strong foundation upon which studies of extracellular matrix molecular expression and tissue ontogeny can be made.