Research Summary
The Fuchs laboratory uses cellular electrophysiology, immunolabeling and electron microscopy to study synaptic connections between sensory hair cells and neurons in the cochlea. One effort focuses on an unusual cholinergic receptor that mediates efferent inhibition of hair cells, driving discovery of the molecular mechanisms, and offering a target for protection against acoustic trauma. A second topic concerns the small number of unmyelinated ‘type II’ afferent neurons whose synaptic connectivity and response properties argue for a role as the pathway for noxious (too loud) sound. Our studies are motivated by curiosity about fundamental mechanisms, and to provide a foundation for understanding cochlear pathogenesis.
Selected Publications
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Fuchs, P.A., T. Nagai and M.G. Evans (1988). Electrical tuning in hair cells isolated from the chick cochlea. Journal of Neuroscience 8:2460-2467.
Fuchs, P.A. and B.W. Murrow (1992a). Cholinergic inhibition of short (outer) hair cells of the chick's cochlea. Journal of Neuroscience. 12(3):800-809.
Fuchs, P.A. and B.W. Murrow (1992b). A novel cholinergic receptor mediates inhibition of chick cochlear hair cells. Proceedings of the Royal Society, London, B 248:35-40.
Martinez-Dunst, C., R. Michaels and P.A. Fuchs (1997). Release sites and calcium channels in hair cells of the chick's cochlea. Journal of Neuroscience 17:9133-9144.
Ramanathan, K., T. Michael, G-J. Jiang, H. Hiel and P.A. Fuchs (1999). A molecular mechanism for the electrical tuning of cochlear hair cells. Science. 283:215-217.
Glowatzki E and PA Fuchs (2000). Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea. Science 288:2366-2368.
Lustig LL, Peng H, Hiel H, Yamamoto T and PA Fuchs (2001). Molecular cloning and mapping of the human nicotinic acetylcholine receptor α10 (CHRNA 10). Genomics 73(3):272-83.
Glowatzki E and PA Fuchs (2002) Transmitter release at the hair cell ribbon synapse. Nature Neuroscience 5(2):147-154.
Katz E, Glowatzki E, Vetter D, Knipper, ME, Gomez-Casati ME, Elgoyhen AB, Fuchs P (2004). Developmental regulation of nicotinic synapses on cochlear inner hair cells. Journal of Neuroscience 24(36):7814-20.
Juan Diego Goutman, Paul Albert Fuchs and Elisabeth Glowatzki (2005). Facilitating efferent inhibition of inner hair cells in the cochlea of the neonatal rat. Journal of Physiology 566: 49-59. PMCID: 1464729.
Philemon S. Yang, Badr A. Alseikhan, Hakim Hiel, Lisa Grant, Masayuki X. Mori, Wanjun Yang, Paul A. Fuchs, and David T. Yue (2006). Switching of Ca2+-Dependent Inactivation of CaV1.3 Channels by Calcium Binding Proteins of Auditory Hair Cells. Journal of Neuroscience 26:10677 – 10689.
Seunghwan Lee, Olga Briklin, Hakim Hiel and Paul A. Fuchs (2007). Calcium-dependent inactivation of calcium channels in cochlear hair cells of the chicken. Journal of Physiology 583 (3):909-922. PMCID: 2277178
Grant, L and Fuchs PA (2008). Calcium, calmodulin-dependent inactivation of calcium channels in inner hair cells of the rat cochlea. Journal of Neurophysiology 99(5):2183-93.
Jee-Hyun Kong, John P. Adelman and Paul A. Fuchs. (2008). Expression of the SK2 calcium-activated potassium channel is required for cholinergic function in cochlear hair cells. Journal of Physiology. 586:5471-85. PMCID: PMC2655383.
Taranda J, Maison SF, Ballestero JA, Katz E, Savino J, Vetter DE, Boulter J, Liberman MC, Fuchs PA, Elgoyhen AB (2009). A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection. PLoS Biol. 2009 Jan 20;7(1):e18. PMCID: 2628405
Weisz C., E. Glowatzki and P.A. Fuchs (2009). The postsynaptic function of type II cochlear afferents. Nature 461:1027-1162. PMID: 19847265; PMCID: PMC2785502. Cited in Faculty of 1000: Andy Groves: Faculty of 1000 Biology, 13 Nov 2009
Wersinger E, J. McLean, P.A. Fuchs and S. J. Pyott (2010) BK channels mediate cholinergic inhibition of high frequency cochlear hair cells. PLoS One. 5(11):e13836. PubMed Central PMCID: PMC2973960.
Jimena Ballestero, Javier Zorrilla de San Martín, Juan Goutman, Ana Belén Elgoyhen, Paul A. Fuchs and Eleonora Katz (2011). Short term synaptic plasticity regulates the level of olivocochlear inhibition to auditory hair cells. Journal of Neuroscience 31(41):14763-74.
Isabelle Roux, Eric Wersinger, J. Michael McIntosh, Paul Fuchs, and Elisabeth Glowatzki (2011). Onset of cholinergic efferent synaptic function in sensory hair cells of the rat cochlea. Journal of Neuroscience 31(42):15092-101. PMCID: PMC3213862.
Marcela Lipovsek, Gi Jung Im, Lucía F. Franchini, Francisco Pisciottano, Eleonora Katz, Paul A. Fuchs, A. Belén Elgoyhen. 2012. Phylogenetic Differences in Calcium Permeability of the α9α10 Cholinergic Nicotinic Receptor. PNAS. 109(11):4308-13. PMCID: PMC3306713
Amanda M. Lauer, Paul Fuchs, David K. Ryugo, Howard W. Francis. Efferent synapses return to aged inner hair cells. 2012 Neurobiology of Aging, 33(12):2892-902. PMCID:PMC3398161
Weisz CJ, Lehar M, Hiel H, Glowatzki E, Fuchs PA. Synaptic transfer from outer hair cells to type II afferent fibers in the rat cochlea. J Neurosci. 2012 Jul11;32(28):9528-36. PubMed PMID: 22787038; PubMed Central PMCID: PMC3433252.
Kong JH, Zachary S, Rohmann KN, Fuchs PA. Retrograde Facilitation of Efferent Synapses on Cochlear Hair Cells. J Assoc Res Otolaryngol. 2012 Nov 27. [Epubahead of print] PubMed PMID: 23183877.
Fuchs PA, Lehar M, Hiel H. Ultrastructure of cisternal synapses on outer hair cells of the mouse cochlea. J Comp Neurol. 2014 522(3):717-29. PubMed PMID: 24122766.
Weisz JC, Glowatzki E, Fuchs PA. (2014). Excitability of type II cochlear afferents. Journal of Neuroscience 34(6):2365-73. PubMed PMID: 24501375; PubMed Central PMCID: PMC3913877
