1983 — 1987 |
Siegel, Jonathan [⬀] Dallos, Peter |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Studies of Cochlear Hair Cell Synaptic Mechanisms @ Northwestern University |
0.915 |
1985 — 2010 |
Dallos, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Studies in Cochlear Hair Cell Transduction @ Northwestern University
DESCRIPTION (Adapted from applicant's abstract): In mammals, outer hair cells provide local amplification in the cochlea that is responsible for the ear's remarkable sensitivity and frequency selectivity. While the reliance of the mammalian cochlea on local, outer hair cell based-based amplification is widely accepted, there is no agreement about the amplifying mechanism. One view is that, powered by the cell's receptor potential, somatic shape changes, called electromotility, provide mechanical feedback and thereby amplification. An alternative concept is that amplification arises as an adjunct to the cell's forward transducer process and thus resides in the sterocilia. We have now identified the gene that codes for the specialized motor protein (prestin) that produces electromotility. Thus, it is now possible to test these alternatives. We shall produce a mouse-model that lacks prestin (knockout mouse) and test its hearing. Normal hearing will imply that the second mechanism of amplification is operative, whereas significant hearing loss will show that due to the non-functional prestin, hearing has been degraded. In addition, extensive experiments are conducted on the molecular properties of prestin itself with aims of producing various antibodies against it, to determine its topology and its interaction with various agents that are known to influence outer hair cell motility.
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1 |
1990 — 2000 |
Dallos, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
In Vitro Studies of Cochlear Neurobiology @ Northwestern University
DESCRIPTION: (Adapted from the Applicant's Abstract.) This project is designed to describe some salient characteristics of mammalian cochlear hair cells. There are two types of such cells in our ears, inner hair cells and outer hair cells. The former are thought to be the true sensory receptors of the ear; they convey auditory information to the central nervous system. Outer hair cells, in contrast, may have primarily a mechanical effector (feedback) role in that they modify the mechanical input to the inner hair cells. To be studied in this project is the stimulus-response relations (electrical response versus hair deflection) for the two hair cell types in isolated organ of Corti segments. Also proposed is to study the mechanical motile response of outer hair cells to electrical stimulation and to hair deflection. These studies are conducted on single isolated outer hair cells for which a real life-like electrical-chemical-mechanical environment is provided. Hair cells are the key elements in the hearing process and their defects are the cause for the vast majority of hearing loss and deafness. Understanding their properties is a prerequisite for the eventual remediation of most hearing disorders.
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1 |
1992 — 2000 |
Dallos, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cochlear Hair Cell Transduction @ Northwestern University
A variety of experiments are designed to examine the operation of the two types of sensory receptor cells of the mammalian hearing organ: inner hair cells and outer hair cells. It is now known that inner hair cells communicate auditory information to the brain, whereas outer hair cells modify the mechanical environment in the cochlea thereby producing amplification. In this work electrical responses to sound are recorded intracellularly from hair cells and extracellularly for their immediate environment in the organ of Corti of anesthetized guinea pigs. A significant portion of the proposed work is aimed at an investigation of the connections between single outer hair cell receptor potentials (their electrical response to sound) and gross extracellular electrical responses. It is proposed that the latter may influence the amplification process at high frequencies. Further, contemporary descriptions are sought of cochlear electroanatomy (its electrical impedance pattern), particularly at high frequencies, and of the organ of Corti proper. Finally, we aim to continue studies designed to evaluate cochlear nonlinear processes (two-tone suppression, low-frequency biasing, combination tone and harmonic production) as reflected in receptor potentials and as influenced by longitudinal location along the cochlear spiral. Aside from its intrinsic interest in describing cochlear nonlinear processing, much of this work is also used diagnostically to evaluate inner versus outer hair cell function and the sources of extracellular responses. A subset of these studies is aimed at finally resolving the long-standing discrepancy in the production of intracellular tonic receptor potentials, generated by outer hair cells in the high versus low frequency regions of the cochlea.
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1 |
1994 — 1995 |
Dallos, Peter J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Cochlear Hair-Cell Transduction @ Northwestern University
There are two types of sensory receptor cell in the mammalian hearing organ (the cochlea), the so-called inner and outer hair cells. Inner hair cells convey most auditory information to the brain, whereas the role of the outer hair cells may be to amplify the input to the inner hair cells. Our work is designed to describe the operation and the role in hearing of these two cell types. Intracellular recordings are made from these cells in anesthetised guinea pigs. Our techniques allow recordings from both cell types and from different locations along the cochlea. This is important because different sound frequencies are processed at different cochlear locations. There is some evidence that the mode of operation of outer hair observations, however, are based on different techniques and, consequently, are not incontrovertible. We intend to use identical techniques in recording from all cochlear locations and thus to ascertain whether or not there are longitudinal differences in outer hair cell function. Without inner hair cells there is no hearing. Without hearing hair cells, hearing is severely deteriorated. There are over 20 million hearing impaired individuals in the U.S. The majority of them suffer their handicap due to hair cell, particularly outer hair cell, damage. An understanding of the neurobiology of hair cells is a key to prevention and eventual remediation of hearing loss. Our work has been and is designed to provide such fundamental understanding.
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1 |
2000 — 2004 |
Dallos, Peter Richter, Claus-Peter [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Micromechanics of the Mammalian Cochlea @ Northwestern University
The sense of hearing results from a series of complex events that transform acoustic pressure waves into the perception of sound. During normal hearing, sound energy is converted to mechanical energy by the middle ear, which then is converted to mechanical motion in the structures of the inner ear, or cochlea. Within the cochlea, the sensory cells-the inner and outer hair cells-are sensitive transducers that convert mechanical vibrations into electrical impulses in the auditory nerve. The resulting nerve impulses are sent to the central auditory nervous system, where they are interpreted and experienced as sound. The sensory hair cells play a critical role in the hearing process. Both inner and outer hair cells have stereocilia located on their apical membranes. Bending of these stereocilia results in a voltage change-or receptor potential-across the cell membrane. The receptor potential in an inner hair cell results in transmitter release from the basal end of the cell. In contrast, the receptor potential in an outer hair cell produces a somatic length change proportional to the membrane voltage change. These length changes in outer hair cells are thought to amplify the sound-induced movements of the cochlear partition. The macromechanics of the hair cell/basilar membrane/organ of Corti system are well described. What remains to be understood is the micromechanics, that is, the mechanical events that take place between displacement of the basilar membrane and deflection of the inner hair cell stereocilia. Using the recently developed hemicochlea preparation, it now is possible to study the micromechanics of the passive cochlea in a radial cross-section. The experiments proposed here are aimed at (1) clarifying the micromechanical processes that transform basilar membrane vibration into deflection of the inner hair cell stereocilia, (2) describing the micromechanical events that result solely from somatic length changes in outer hair cells, (3) investigating the effect of electrical stimulation on different cell types in the cochlea, (4) examining the interactions between somatic length changes of outer hair cells and the vibration of the basilar membrane known to occur in vivo, and (5) providing empirical data for finite-element models of the cochlea.
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0.915 |