Mark A. Rutherford, Ph.D.

Assistant Professor
Otolaryngology

Neurosciences Program

Research Abstract:

As auditory neurobiologists, our work focuses on cellular mechanisms that underlie our systems of sound and balance encoding in development, in maturity, and in conditions of hearing or vestibular loss/dysfunction. It is my hope that through a better understanding of what makes hearing and balance happen, we will better understand how to protect and restore it. Some short and long-term goals of the Rutherford Lab:
1) The molecular anatomy of synapses between mammalian hair cells and auditory nerve fibers is being elucidated. Using advanced microscopy techniques, with quantitative molecular specificity we are relating inner ear synaptic structures to the afferent and efferent functions of hearing.
2) Physiological mechanisms of synaptic transmission and action potential generation that underlie sensory encoding are being studied with state-of-the-art patch-clamp electrophysiology on sensory hair cells and auditory nerve fibers.
3) Primary neural degeneration in the auditory nerve that occurs in response to noise damage or with aging is being studied with experiments that aim to identify the mechanisms of glutamate-induced excitotoxicity in nerve fibers of the cochlea.
4) The roles of cochlear efferent neurotransmitters (e.g., dopamine, GABA) in membrane excitability and protection from noise-induced and age-related hearing loss will be investigated at the cellular and systems levels with structural and functional studies that utilize mammalian genetics.
5) Development of better cochlear prosthetics will be pursued using intracellular recording and cochlear implant-like stimulation of the auditory nerve.
6) Postsynaptic Ca2+ and Na+ imaging will be established for optical measurements of spiral ganglion neuron activity.

Collaborations within the excellent research environment at Washington University are helping to advance these aims.

Selected Publications:

Rutherford, M.A., Moser, T. “The Ribbon Synapse Between Type I Spiral Ganglion Neurons and Inner Hair Cells.” In: Springer Handbook of Auditory Research, Volume 52: The Primary Auditory Neurons of the Mammalian Cochlea. Springer-Verlag New York Eds. Dabdoub, A., Fritzsch, B., Popper, A.N., Fay, R.R. (2016) DOI: 10.1007/978-1-4939-3031-9

Lars Becker, Michael E. Schnee, Mamiko Niwa, Willy Sun, Stephan Maxeiner, Sara Talaei, Bechara Kachar, Mark A. Rutherford, Anthony J. Ricci. The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse. eLife, 7, e30241 (2018). PMID: 29328021

Sebe, J.Y., Cho, S., Sheets, L., Rutherford, M.A., von Gersdorff, H., and Raible, D.W. Ca2+-Permeable AMPARs Mediate Glutamatergic Transmission and Excitotoxic Damage at the Hair Cell Ribbon Synapse. J Neurosci 37.25 (2017): 6162-6175. PMID: 28539424

Hirose, K., Rutherford, M.A., and Warchol, M.E. Two cell populations participate in clearance of damaged hair cells from the sensory epithelia of the inner ear. Hearing Research 352: 70 (2017). PMID: 28526177

Ohn, T.L., Rutherford, M.A., Jing, Z., Jung, S., Duque-Afonso, C.J., Hoch, G., Picher, M.M., Scharinger, A., Strenzke, N., and Moser, T. Hair Cells Use Active Zones with Different Voltage Dependence of Ca2+ Influx to Decompose Sounds into Complementary Neural Codes. PNAS 113(32): E4716 (2016) PMID: 27462107

Kim, Kyunghee X., Rutherford, M.A. Maturation of NaV and KV Channel Topographies in the Auditory Nerve Spike Initiator before and after Developmental Onset of Hearing Function. J Neurosci 36(7): 2111 (2016) PMID: 26888923

Rutherford, M.A. Resolving the Structure of Inner Ear Ribbon Synapses with STED Microscopy. Synapse, 69(5):242 (2015) PMID: 25682928

Wong, A.B., Rutherford, M.A., Gabrielaitis, M., Pangršič, T., Göttfert, F., Frank, T., Michanski, F., Hell, S., Wolf, F., Wichman, C., Moser, T. Developmental Refinement of Hair Cell Synapses Tightens the Coupling of Ca2+ Influx to Exocytosis. EMBO J 33(3):247 (2014) PMID: 24442635

Wong, A.B., Jing, Z., Rutherford, M.A., Frank, T., Strenzke, N., Moser, T. Concurrent Maturation of Inner Hair Cell Synaptic Ca2+ Influx and Auditory Nerve Spontaneous Activity around Hearing Onset in Mice. J Neurosci 33(26):10661 (2013) PMID: 23804089

Jing, Z., Rutherford, M.A., Takago, H., Frank, T., Fejtova, A., Khimich, D., Moser, T., Strenzke, N. Disruption of the Presynaptic Cytomatrix Protein Bassoon Degrades Ribbon Anchorage, Multi-quantal Release, and Sound Encoding at the Hair Cell Afferent Synapse. J Neurosci 33(10):4456 (2013) PMID: 23467361

von Ameln, S., Wang, G., Boulouiz, R., Rutherford, M.A., Smith, G.M., Li, Y., Pogoda, H.M., Nürnberg, G., Volk, A.E., Stiller, B., Hong, J.S., Goodyear, R.J., Nürnberg, P., Richardson, G.P., Hammerschmidt, M., Moser, T., Wollnik, B., Koehler, C.M., Teitell, M.A., Barakat, A., Kubisch, C. A Mutation in PNPT1, Encoding Mitochondrial-RNA-Import Protein PNPase, Causes Hereditary Hearing Loss. The American Journal of Human Genetics 91(5):919 (2012) PMID: 23084290

Rutherford, M.A., Pangrsic, T. Molecular Anatomy and Physiology of Exocytosis in Sensory Hair Cells. Cell Calcium 52(3-4):327 (2012) PMID: 22682011

Rutherford, M.A., Chapochnikov, N.M., Moser, T. Spike Encoding of Neurotransmitter Release Timing by Spiral Ganglion Neurons of the Cochlea. J Neurosci 32(14):4773 (2012) PMID: 22492033

Last Updated: 7/31/2018 7:54:41 AM

Glutamate is required for hearing, but too much glutamate is toxic. Rutherford Lab is studying the different types of glutamate receptors that underlie hearing and excitotoxicity.
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