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Peter Dallos
John Evans Professor
PhD, Northwestern
  Biophysics and Neurobiology of the Cochlea
e-mail Dr. Dallos
ph: 847.491.3175
fax: 847.467.4327

In our early work, using techniques ranging from behavioral studies to single-cell recordings, we have studied such topics as the relation between gross cochlear and neural potentials and their unit precursors, the properties and nature of cochlear summating potentials, nonlinear properties of the cochlea as reflected in electrical responses, analysis of the electrical network properties of the organ of Corti, and various aspects of neural coding at the single-fiber level. Subsequently, our primary aim was to delineate the physiological properties and functional roles of the two types of sensory receptors of the mammalian organ of Corti, inner and outer hair cells. These inquiries were first pursued by indirect means. Using ototoxic antibiotics, we destroyed portions of the outer hair cell population and studied the effects with behavioral and electrophysiological methods. This work yielded the now commonly accepted conclusion that outer hair cells provide local amplification in the cochlea. A later, more direct approach employed intracellular recordings from inner and outer hair cells in vivo. Using this technique, we produced the first recording from outer hair cells and have been able to describe numerous basic properties of hair-cell function. In vivo recordings continue and they have been supplemented during the past twenty years with a variety of in vitro approaches. Among these is a major experimental series on isolated outer hair cells using the microchamber and whole-cell patch-clamp methods. We have investigated various aspects of electromotility, such as the nature and distribution of the molecular motors responsible for changes in cell length, the ontogeny of electromotility, the process of modulation of electromotility by efferent neurotransmitters and a search for the cellular mechanisms of such modulation. We also demonstrated somatic shape changes upon mechanical deflection of the cells' hair bundle. Another discovery is that the somatic stiffness of outer hair cells is voltage dependent and highly correlated with electromotility. We had a major effort addressing cochlear micromechanics, that is, the motion pattern of cellular elements within the organ of Corti. We have developed a "hemicochlea" preparation and computer vision techniques that are ideally suited to describe dynamic behavior in the passive organ of Corti and provide quantitative depictions, for the first time, of the motion pattern of any component in given cochlear cross-sections. Our current work is fully engaged with the properties of prestin and on its role in cochlear mechanical feedback amplification.

Selected References:

• Oliver, D., D.Z.Z. He, N. Klöcker, J. Ludwig, U. Schulte, S. Waldegger, J.P. Ruppersberg, P. Dallos, and B. Fakler. Intracellular anions as the voltage-sensor of prestin, the outer hair cell motor protein. Science 292, 2340-2343 (2001). [full text]

• Santos-Sacchi, J., Shen, W., Zheng, J. and Dallos, P. Effects of membrane potential and tension on prestin, the outer hair cell membrane protein. J. Physiol. (London) 531, 661-666 (2001). [full text]

• Zheng, J., W. Shen, D.Z.Z. He, K. Long, L.D. Madison and P. Dallos. Prestin is the motor protein of cochlear outer hair cells. Nature 405, 149-155 (2000). [full text]

• He, D.Z.Z. and P. Dallos. Somatic stiffness of cochlear outer hair cells is voltage dependent. Proc.Natl.Acad.Sci.USA 96: 8223-8228 (1999). [full text]

• Richter, C.P., B.N. Evans, R. Edge and P. Dallos. Basilar membrane vibration in the gerbil hemicochlea. J. Neurophysiol. 59: 2255-2264 (1998). [full text]

• Dallos, P., D.Z.Z. He, I. Sziklai, X. Lin, S. Mehta and B.N. Evans. Acetylcholine, outer hair cell electromotility, and the cochlear amplifier. J. Neurosci. 15: 2212-2226 (1997). [full text]

• Dallos, P. and B. N. Evans. High-frequency motility of outer hair cells and the cochlear amplifier. Science 267: 2006-2009 (1995).

 

 
TSA201 cells Left: Examples of voltage-dependent motility expressed in TSA201 cells transiently transfected with Prestin. Top: Video image of a TSA201 cell partially drawn into a microchamber. Motility was measured electro-optically by monitoring light intensity through a slit placed at the farthest excluded membrane segment. Bottom: Top two traces: motile responses from two transfected cells. Third trace: lack of motile response from cell transfected with control plasmid only. Fourth trace: stimulus waveform. [after Zheng et al., Nature, 405: 149-155, 2000]