John J Guinan
Massachusetts Eye And Ear Infirmary
Project start date: 1984-06-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
OLIVOCOCHLEAR EFFERENT SYSTEMS
John J Guinan, Principal Research Scientist
Massachusetts Eye And Ear Infirmary
243 Charles St
boston, Ma 021143096
Grant 5R01DC000235-14 from National Institute On Deafness And Other Communication Disorders IRG: HAR
Abstract: The medial olivocochlear efferent system is almost universally present in mammalian auditory systems, yet the mechanisms by which it acts and its functional significance are still unclear. Our previous work suggests that efferent inhibition observed at low and high sound levels may have entirely different physiological bases, the former through the outer-hair- cell (OHC) synaptic conductance shunting OHC receptor currents, the latter through electrical effects on inner hair cells and afferent neurons. An analysis of the implications of these low and high sound level mechanisms, and our preliminary results, indicate that current views about the pattern of efferent effects with changes in sound frequency, sound level, efferent firing rate, and the number of efferents firing are fundamentally incorrect. The proposed experimental work will test specific hypotheses, formulated from our past work, about the mechanisms of efferent inhibition both at low sound levels and at high sound levels. The data obtained will generate a new and more complex picture of how discharge patterns in auditory nerve fibers are affected by various levels of efferent activity. These data will enable us to predict how sensory input from the ear is modified under many different conditions so that functional consequences can be deduced. This knowledge should aid in understanding both normal and pathological hearing and add to the growing understanding of feedback control systems in neurobiology
Keywords: acoustic nerve (VIII), auditory pathway, cochlea, efferent nerve, neural inhibition, olivocochlear bundle action potential, auditory stimulus, biological model, brain stem, cochlear microphonic potential, ear hair cell, electrophysiology, electrostimulus, sound, stimulus /response cat, histochemistry /cytochemistry, single cell analysis
Project start date: 1984-06-01
Project end date: 2000-09-29
5R01DC000235-14 (1999): $286107
5R01DC000235-13 (1998): $273426
5R01DC000235-12 (1997): $276880
Olivocochlear Efferent Systems And Cochlear Physiology
John J Guinan, Principal Research Scientist
Massachusetts Eye And Ear Infirmary 243 Charles St Boston, Ma 021143096
Grant 5R01DC000235-20 from National Institute On Deafness And Other Communication Disorders IRG: AUD
Abstract: Our goal is to understand how outer hair cells (OHCs) produce the high sensitivity of mammalian hearing. Great progress has been made in understanding the properties of isolated OHCs, but there are fundamental unanswered questions about how OHCs work in intact cochleas. Medial olivocochlear (MOC) efferent neurons innervate OHCs and provide an important tool for understanding OHC-based mechanisms. To study the mechanical effects of OHCs in vivo, we will measure basilar-membrane (BM) motion and auditory-nerve (AN) firing patterns and the changes produced in these responses by electrical stimulation of MOC efferents. Our recent work provides strong evidence for the existence of a second traveling wave along the cochlea, a wave that may couple OHC motility to BM motion. The proposed work will characterize the properties of this second wave and its relationship to the classic transverse traveling wave. This wil be done (1) at frequencies well below the local characteristic frequency (CF), where stiffness dominates the mechanical response and the effects of the two traveling waves can be studied without the complications produced by cochlear amplification, and (2) at frequencies near CF where the cochlear amplifier has its primary effects. Our work, and that of others, has shown that the "slow effect" of MOC stimulation is due to a decrease in OHC stiffness. This stiffness change will be exploited to determine how OHC stiffness affects cochlear properties such as CF, and to test the OHC piezoelectric theory, a theory that may account for how OHC somatic motility can be effective at frequencies above the OHC membrane cut-off frequency. The results of the proposed work will help to flesh out a new picture of cochlear mechanics. Mechanics is a key area of cochlear function that is disrupted by many of the pathologies that affect hearing. Understanding cochlear mechanics, and the role of OHCs in cochlear mechanics, is essential for progress in almost all aspects of hearing.
Keywords: acoustic nerve, auditory pathway, cochlea, efferent nerve, neural information processing, olivocochlear bundle, action potential, auditory stimulus, auditory threshold, biomechanics, cochlear microphonic potential, ear hair cell, sound frequency, cat, guinea pig
Project start date: 1984-06-01
Project end date: 2007-12-31
5R01DC000235-20 (2007): $220490
5R01DC000235-19 (2006): $227075
OLIVOCOCHLEAR EFFERENT SYSTEMS
John J Guinan, Principal Research Scientist
Electrical Engineering And Computer Sciencemassachusetts Institute Of Technology
77 Massachusetts Ave
cambridge, Ma 02139
Grant 5R01DC000235-10 from National Institute On Deafness And Other Communication Disorders IRG: CMS
Abstract: Investigator´s ) The investigators propose a series of measurements to address many theoretically important issues at the level of cellular interactions in the intact cochlea using the action of medial olivocochlear efferents as a tool. A subsidiary goal is to understand the changes produced by efferents in stimulus coding in the auditory nerve. The data obtained should provide significant new insights relevant to such questions as What events control the firing of auditory-nerve fibers? Does efferent activity act in part through a change in endocochlear potential? What factors make responses of auditory-nerve fibers with high spontaneous firing rates different from those with low spontaneous rates? What changes in firings of auditory-nerve fibers are produced by efferent activity when sounds are well above threshold and not at the fiber characteristic frequency (CF)? How is two-tone suppression produced, and how is it influenced by efferent activity? How are otacoustic emissions generated, and how does efferent activity affect them? How do the time courses of various efferent effects relate to one another and to the underlying efferent actions which give rise to these effects? How large are the effects of a single efferent fiber on auditory-nerve responses, and how do these effects summate? The investigators will address these questions by 1 comparing efferent-evoked effects on auditory-nerve fibers with different Sirs but the same CF from the same cat, 2 measuring both mechanical and neural effect of two-tone suppression and comparing these effects with those efferent stimulation. 3 measuring the time courses of medial-efferent effects (mechanical, electrical and neural) in response to trains of shock, and 4. determining the correspondence between the number of medial efferents that fire and the effects produced. Changes in cochlear mechanics will be monitored by measuring changes in stimulus frequency emissions and efferent-evoked electrical changes will be monitored by measuring changes in endocochlear potential
Keywords: acoustic nerve (VIII), auditory pathway, cochlea, efferent nerve, olivocochlear bundle auditory stimulus, biological model, cochlear microphonic potential, electrophysiology, electrostimulus, sound, stimulus /response cat, histochemistry /cytochemistry, single cell analysis
Project start date: 1984-06-01
Project end date: 1996-03-31
5R01DC000235-10 (1994): $159481
5R01DC000235-09 (1993): $313768
OLIVOCOCHLEAR EFFERENT SYSTEMS AND COCHLEAR PHYSIOLOGY
John J Guinan, Principal Research Scientist
Massachusetts Eye And Ear Infirmary
243 Charles St
boston, Ma 021143096
Grant 5R01DC000235-16 from National Institute On Deafness And Other Communication Disorders IRG: ZRG1
Abstract: Adapted from applicant´s ) Despite great progress in understanding many aspects of cochlear function, knowledge in the key area of cochlear micromechanics is rudimentary and knowledge of apical macromechanics is almost absent. In the conventional view, basilar-membrane motion bends inner-hair-cell (IHC) stereocilia by a single vibrational pattern and there is a single traveling wave along the basilar-membrane. However, this view does not fit with our recent work which shows there are multiple excitation drives or with mechanical and neural data showing multiple group delays in the apex. Several lines of evidence point to a new conception of cochlear micromechanics in which the organ of Corti vibrates in modes, each with its own resonant frequency and each providing an excitation drive to IHC stereocilia. With the cochlear partition allowed to move in multiple, overlapping motions, there can be multiple traveling waves. Recordings from single auditory-nerve fibers reveal the multiple resonances and are ideally suited for tracking these resonances along the cochlea. The proposed work will (1) distinguish the excitation drives that affects the responses of individual auditory-nerve fibers, map them along the cochlea, and determine their traveling wave velocities, (2) determine how these resonances are affected by efferent stimulation and low-frequency "bias" tones, and (3) test the hypothesis that a profound cochlear nonlinearity control the transition between certain modes. The proposed experiments will test the hypothesis suggested by our preliminary results that there ate two overlapping traveling waves. Our results will provide data that will flesh out a new picture of cochlear mechanics and provide a rich source of data for the formation of new experiments, and new models for the biophysical and cell-biological basis of the cochlear resonances. Since auditory-nerve-fiber experiment do not invade the cochlea, our characterization of the resonant modes present in an intact, normally-functioning cochlea will provide a gold standard that can be used to determine the normally of the modes seen and any invasive experiment. Obtaining an overall functional characterization at this pivotal mechanical level is essential for understanding how outer -hair-cell motility and other cellular and structure properties of the cochlea produce the cochlear amplifier and lead to output of the cochlea
Keywords: acoustic nerve, auditory pathway, cochlea, efferent nerve, olivocochlear bundle action potential, auditory stimulus, auditory threshold, biomechanics, cochlear microphonic potential, ear hair cell, sound frequency cat
Project start date: 1984-06-01
Project end date: 2003-08-31
5R01DC000235-16 (2001): $278240
5R01DC000235-23 (2010): $254133
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to John J Guinan
Olivocochlear Efferent Systems And Cochlear Physiology
John J Guinan, Principal Research Scientist
Massachusetts Eye And Ear Infirmary 243 Charles St Boston, Ma 021143096
Grant 2R01DC000235-18 from National Institute On Deafness And Other Communication Disorders IRG: AUD
Abstract: Our goal is to understand how outer hair cells (OHCs) produce the high sensitivity of mammalian hearing. Great progress has been made in understanding the properties of isolated OHCs, but there are fundamental unanswered questions about how OHCs work in intact cochleas. Medial olivocochlear (MOC) efferent neurons innervate OHCs and provide an important tool for understanding OHC-based mechanisms. To study the mechanical effects of OHCs in vivo, we will measure basilar-membrane (BM) motion and auditory-nerve (AN) firing patterns and the changes produced in these responses by electrical stimulation of MOC efferents. Our recent work provides strong evidence for the existence of a second traveling wave along the cochlea, a wave that may couple OHC motility to BM motion. The proposed work will characterize the properties of this second wave and its relationship to the classic transverse traveling wave. This wil be done (1) at frequencies well below the local characteristic frequency (CF), where stiffness dominates the mechanical response and the effects of the two traveling waves can be studied without the complications produced by cochlear amplification, and (2) at frequencies near CF where the cochlear amplifier has its primary effects. Our work, and that of others, has shown that the "slow effect" of MOC stimulation is due to a decrease in OHC stiffness. This stiffness change will be exploited to determine how OHC stiffness affects cochlear properties such as CF, and to test the OHC piezoelectric theory, a theory that may account for how OHC somatic motility can be effective at frequencies above the OHC membrane cut-off frequency. The results of the proposed work will help to flesh out a new picture of cochlear mechanics. Mechanics is a key area of cochlear function that is disrupted by many of the pathologies that affect hearing. Understanding cochlear mechanics, and the role of OHCs in cochlear mechanics, is essential for progress in almost all aspects of hearing.
Keywords: acoustic nerve, auditory pathway, cochlea, efferent nerve, neural information processing, olivocochlear bundle, action potential, auditory stimulus, auditory threshold, biomechanics, cochlear microphonic potential, ear hair cell, sound frequency, cat, guinea pig
Project start date: 1984-06-01
Project end date: 2007-12-31
2R01DC000235-18 (2005): $232540
OLIVOCOCHLEAR EFFERENT SYSTEMS
John J Guinan, Principal Research Scientist
Massachusetts Institute Of Technology 77 Massachusetts Ave Cambridge, Ma 02139
Grant 2R01DC000235-07A2 from National Institute On Deafness And Other Communication Disorders IRG: CMS
Abstract: Investigator s ) The investigators propose a series of measurements to address many theoretically important issues at the level of cellular interactions in the intact cochlea using the action of medial olivocochlear efferents as a tool. A subsidiary goal is to understand the changes produced by efferents in stimulus coding in the auditory nerve. The data obtained should provide significant new insights relevant to such questions as What events control the firing of auditory-nerve fibers? Does efferent activity act in part through a change in endocochlear potential? What factors make responses of auditory-nerve fibers with high spontaneous firing rates different from those with low spontaneous rates? What changes in firings of auditory-nerve fibers are produced by efferent activity when sounds are well above threshold and not at the fiber characteristic frequency (CF)? How is two-tone suppression produced, and how is it influenced by efferent activity? How are otacoustic emissions generated, and how does efferent activity affect them? How do the time courses of various efferent effects relate to one another and to the underlying efferent actions which give rise to these effects? How large are the effects of a single efferent fiber on auditory-nerve responses, and how do these effects summate? The investigators will address these questions by 1 comparing efferent-evoked effects on auditory-nerve fibers with different Sirs but the same CF from the same cat, 2 measuring both mechanical and neural effect of two-tone suppression and comparing these effects with those efferent stimulation. 3 measuring the time courses of medial-efferent effects (mechanical, electrical and neural) in response to trains of shock, and 4. determining the correspondence between the number of medial efferents that fire and the effects produced. Changes in cochlear mechanics will be monitored by measuring changes in stimulus frequency emissions and efferent-evoked electrical changes will be monitored by measuring changes in endocochlear potential.
Keywords: acoustic nerve (VIII), auditory pathway, cochlea, efferent nerve, olivocochlear bundle, auditory stimulus, biological model, cochlear microphonic potential, electrophysiology, electrostimulus, sound, stimulus /response, cat, histochemistry /cytochemistry, single cell analysis
Project start date: 1984-06-01
Project end date: 1995-06-30
OLIVOCOCHLEAR REFLEX IN HUMANS
John J Guinan, Principal Investigator
Massachusetts Eye And Ear Infirmary, 243 Charles St, Boston, Ma 02114-3096
Grant 5R01DC005977-07 from National Institute On Deafness And Other Communication Disorders
Abstract: Despite work by many investigators, we still do not know the functional role of medial olivocochlear (MOC) efferents. In previous attempts to correlate MOC strength with subject performance, the passive response of the MOC acoustic reflex was measured, not the MOC activation during the task. We are now able to measure MOC activation during a psychophysical task, a new paradigm that greatly increases our ability to test MOC function and descending control in the human auditory system. MOC tests based on otoacoustic emission (OAE) measurements are being used both scientifically and clinically, but the accuracy of such tests has never been ascertained. To maximize the scientific and clinical usefulness of OAE tests we will Aim (1A,B) Measure MOC effects using the three types of evoked OAEs and compare the resulting MOC-strength metrics in terms of signal/noise ratios and accuracy of subject ranking, using both contralateral and ipsilateral elicitors, and Aim (1C) determine, in humans, MOC reflex strength in terms of changes in cochlear sensitivity, as shown by MOC-induced changes in wave I of the auditory brainstem response. To address the functional significance of the MOC system, we will systematically measure MOC activation levels in psychophysical tasks (Aim 2A-C) in which MOC activation is expected to aid performance (discrimination of transient signals in noise) vs. those in which no benefit is anticipated, and (Aim 2D-E) to determine MOC frequency selectivity in an active task. The MOC strength tests developed in this work should be useful in clinical and scientific contexts to predict susceptibility to noise damage, in the diagnosis and tracking of diseases, in evaluating the toxicity of drugs and to show the role of MOC feedback in normal hearing. The proposed work will also help to indicate the extent to which such feedback should be put in hearing aids and prosthetic devices such as cochlear implants. The proposed work will develop and evaluate otoacoustic emission tests for the strength of medial olivocochlear (MOC) efferent feedback to the cochlea. MOC strength tests are useful in clinical and scientific contexts to predict susceptibility to noise damage, in the diagnosis and tracking of diseases, in evaluating the toxicity of drugs and to show the role of MOC feedback in normal hearing. The proposed work will also help to indicate the extent to which such feedback should be put in hearing aids and prosthetic devices such as cochlear implants. 1
Keywords: Acoustic Nerve; Address; Animals; Attention; Auditory Brainstem Responses; Auditory Prosthesis; Auditory system; C 2a; C2a; Cell Communication and Signaling; Cell Signaling; Clinical; Cochlea; Cochlear Implants; Cochlear Organ; Cochlear Prosthesis; Cochlear structure; Cognitive Discrimination; Contralateral; Cranial Nerve Eight; Cranial Nerve VIII; Diagnosis; Discrimination; Discrimination (Psychology); Disease; Disorder; Drug toxicity; Ear; Ear structure; Eighth Cranial Nerve; Feedback; Frequencies (time pattern); Frequency; Grant; Hearing; Hearing Aids; Human; Human, General; Individual; Intracellular Communication and Signaling; Investigators; Ipsilateral; Judgment; Learning; Man (Taxonomy); Man, Modern; Measurement; Measures; Medial; Methods; Metric; Nervous; Noise; Otoacoustic Emissions, Spontaneous; Pattern; Performance; Peripheral; Predisposition; Prosthesis; Prosthetic device; Prosthetics; Psychology, Physiologic; Psychology, Physiological; Psychophysiological; Psychophysiology; Public Health; Publishing; Reflex; Reflex action; Research; Research Personnel; Researchers; Role; Signal Transduction; Signal Transduction Systems; Signaling; Spontaneous Otoacoustic Emissions; Susceptibility; System; System, LOINC Axis 4; Testing; VIIIth Cranial Nerve; Vestibulocochlear Nerve; Work; acoustic reflex; auditory nerve; base; biological signal transduction; clinical applicability; clinical application; complement 2a; complement C2a; complement C2a fragment; design; designing; disease/disorder; hearing perception; indexing; neural; otoacoustic emission; psycho-physiological; public health medicine (field); public health relevance; relating to nervous system; response; social role; sound perception
Relevance: Olivocochlear Reflex in Humans PHS statement (Using no more than two or three sentences, describe the relevance of this research to public health.) The proposed work will develop and evaluate otoacoustic emission tests for the strength of medial olivocochlear (MOC) efferent feedback to the cochlea. MOC strength tests are useful in clinical and scientific contexts to predict susceptibility to noise damage, in the diagnosis and tracking of diseases, in evaluating the toxicity of drugs and to show the role of MOC feedback in normal hearing. The proposed work will also help to indicate the extent to which such feedback should be put in hearing aids and prosthetic devices such as cochlear implants. 1
Project start date: 2003-04-01
Project end date: 2014-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-07-070
5R01DC005977-07 (2010): $328711
2R01DC005977-06A1 (2009): $325657
5R01DC005977-05 (2007): $235936
5R01DC005977-04 (2006): $242983
5R01DC005977-03 (2005): $248830
5R01DC005977-02 (2004): $248830
1R01DC005977-01 (2003): $259750
OLIVOCOCHLEAR EFFERENT SYSTEMS AND COCHLEAR PHYSIOLOGY
John J Guinan, Principal Research Scientist
Massachusetts Eye And Ear Infirmary 243 Charles St Boston, Ma 021143096
Grant 2R01DC000235-15A1 from National Institute On Deafness And Other Communication Disorders IRG: ZRG1
Abstract: Adapted from applicant s ) Despite great progress in understanding many aspects of cochlear function, knowledge in the key area of cochlear micromechanics is rudimentary and knowledge of apical macromechanics is almost absent. In the conventional view, basilar-membrane motion bends inner-hair-cell (IHC) stereocilia by a single vibrational pattern and there is a single traveling wave along the basilar-membrane. However, this view does not fit with our recent work which shows there are multiple excitation drives or with mechanical and neural data showing multiple group delays in the apex. Several lines of evidence point to a new conception of cochlear micromechanics in which the organ of Corti vibrates in modes, each with its own resonant frequency and each providing an excitation drive to IHC stereocilia. With the cochlear partition allowed to move in multiple, overlapping motions, there can be multiple traveling waves. Recordings from single auditory-nerve fibers reveal the multiple resonances and are ideally suited for tracking these resonances along the cochlea. The proposed work will (1) distinguish the excitation drives that affects the responses of individual auditory-nerve fibers, map them along the cochlea, and determine their traveling wave velocities, (2) determine how these resonances are affected by efferent stimulation and low-frequency "bias" tones, and (3) test the hypothesis that a profound cochlear nonlinearity control the transition between certain modes. The proposed experiments will test the hypothesis suggested by our preliminary results that there ate two overlapping traveling waves. Our results will provide data that will flesh out a new picture of cochlear mechanics and provide a rich source of data for the formation of new experiments, and new models for the biophysical and cell-biological basis of the cochlear resonances. Since auditory-nerve-fiber experiment do not invade the cochlea, our characterization of the resonant modes present in an intact, normally-functioning cochlea will provide a gold standard that can be used to determine the normally of the modes seen and any invasive experiment. Obtaining an overall functional characterization at this pivotal mechanical level is essential for understanding how outer -hair-cell motility and other cellular and structure properties of the cochlea produce the cochlear amplifier and lead to output of the cochlea.
Keywords: acoustic nerve (VIII), auditory pathway, cochlea, efferent nerve, olivocochlear bundle, action potential, auditory stimulus, auditory threshold, biomechanics, cochlear microphonic potential, ear hair cell, sound frequency, cat
Project start date: 1984-06-01
Project end date: 2003-08-31
2R01DC000235-15A1 (2000): $278240
Sponsored Links Excellgen http://Excellgen.com
John J Guinan, Principal Investigator
Massachusetts Eye And Ear Infirmary, 243 Charles St, Boston, Ma 02114-3096
Keywords: Acoustic; Acoustics; Advertising; Artifacts; Auditory; Auditory Physiology; Communities; Complex; Computer Programs; Computer software; Computers; Custom; Deafness; Devices; Electrodes; Electronics; Engineering; Engineerings; Environment; Equipment; Funding; Generations; Hearing; Image; Individual; Internet; Investigators; Knowledge; Laboratories; Mechanics; Methods and Techniques; Methods, Other; Morphologic artifacts; NIH; National Institutes of Health; National Institutes of Health (U.S.); Output; Physiologic; Physiological; Publishing; R01 Mechanism; R01 Program; RPG; Research; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Researchers; Role; Science; Scientific Advances and Accomplishments; Software; Solutions; Stimulus; System; System, LOINC Axis 4; Techniques; Technology; United States National Institutes of Health; WWW; Work; Writing; computer program/software; data acquisition; design; designing; experiment; experimental research; experimental study; flexibility; hearing perception; imaging; instrument; interest; meetings; repair; repaired; research study; scientific accomplishments; scientific advances; social role; software systems; sound perception; web; web site; world wide web
Budget start date: 17-JUL-2009
Budget end date: 31-MAY-2011
3P30DC005209-08S1_9001 (2009): $247579
5P30DC005209-08_9001 (2009): $410267
OLIVOCOCHLEAR EFFERENT SYSTEMS
John J Guinan, Principal Research Scientist
Massachusetts Eye And Ear Infirmary 243 Charles St Boston, Ma 021143096
Grant 2R01DC000235-11A1 from National Institute On Deafness And Other Communication Disorders IRG: HAR
Project start date: 1984-06-01
Project end date: 2000-03-31
2R01DC000235-11A1 (1996): $215743