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Sensory signaling and ontogeny. as related to molecular mechanisms that regulate auditory functionOne 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. Neuronal codingThe 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. Tissue morphogenesisTo 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. Selected PublicationsFlores-Otero J, Xue HZ, Davis RL. (2007) Reciprocal regulation of presynaptic and postsynaptic proteins in bipolar spiral ganglion neurons by neurotrophins. J Neurosci. 27(51):14023-34. Liu Q, Davis RL. (2007) Regional specification of threshold sensitivity and response time in CBA/CaJ mouse spiral ganglion neurons. J Neurophysiol. 98(4):2215-22. Beisel KW, Rocha-Sanchez SM, Ziegenbein SJ, Morris KA, Kai C, Kawai J, Carninci P, Hayashizaki Y, Davis RL. (2007) Diversity of Ca2+-activated K+ channel transcripts in inner ear hair cells. Gene. 386(1-2):11-23. Chen WC, Davis RL. (2006) Voltage-gated and two-pore-domain potassium channels in murine spiral ganglion neurons. Hear Res. 222(1-2):89-99. Zhou Z. Liu Q. Davis RL. (2005) Complex regulation of spiral ganglion neuron firing patterns by neurotrophin-3. J Neurosci. 25(33):7558-66. Reid MA. Flores-Otero J. Davis RL. (2004) Firing patterns of type II spiral ganglion neurons in vitro. J Neurosci. 24(3):733-42. Davis RL. (2003) Gradients of neurotrophins. ion channels. and tuning in the cochlea. Neuroscientist. 9(5):311-6. Review. Mo ZL. Adamson CL. Davis RL. (2002) Dendrotoxin-sensitive K(+) currents contribute to accommodation in murine spiral ganglion neurons. J Physiol. 542 (Pt 3):763-78. Adamson CL. Reid MA. Mo ZL. Bowne-English J. Davis RL. (2002) Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location. J Comp Neurol. 447(4):331-50. Adamson CL. Reid MA. Davis RL. (2002) Opposite actions of brain-derived neurotrophic factor and neurotrophin-3 on firing features and ion channel composition of murine spiral ganglion neurons. J Neurosci. 22(4):1385-96. |
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