The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Charles C. Della Santina - One of the best experts on this subject based on the ideXlab platform.
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Virtual Rhesus Labyrinth Model Predicts Responses to Electrical Stimulation Delivered by a Vestibular Prosthesis
Journal of the Association for Research in Otolaryngology, 2019Co-Authors: Abderrahmane Hedjoudje, Russell Hayden, Susumu Mori, Chenkai Dai, Joongho Ahn, Mehdi Rahman, Frank Risi, Jiangyang Zhang, Charles C. Della SantinaAbstract:To better understand the spread of prosthetic current in the inner ear and to facilitate design of electrode arrays and stimulation protocols for a Vestibular implant system intended to restore sensation after loss of Vestibular Hair Cell function, we created a model of the primate labyrinth. Because the geometry of the implanted ear is complex, accurately modeling effects of prosthetic stimuli on Vestibular afferent activity required a detailed representation of labyrinthine anatomy. Model geometry was therefore generated from three-dimensional (3D) reconstructions of a normal rhesus temporal bone imaged using micro-MRI and micro-CT. For systematically varied combinations of active and return electrode location, the extraCellular potential field during a biphasic current pulse was computed using finite element methods. Potential field values served as inputs to stochastic, nonlinear dynamic models for each of 2415 Vestibular afferent axons, each with unique origin on the neuroepithelium and spiking dynamics based on a modified Smith and Goldberg model. We tested the model by comparing predicted and actual 3D vestibulo-ocular reflex (VOR) responses for eye rotation elicited by prosthetic stimuli. The model was individualized for each implanted animal by placing model electrodes in the standard labyrinth geometry based on CT localization of actual implanted electrodes. Eye rotation 3D axes were predicted from relative proportions of model axons excited within each of the three ampullary nerves, and predictions were compared to archival eye movement response data measured in three alert rhesus monkeys using 3D scleral coil oculography. Multiple empirically observed features emerged as properties of the model, including effects of changing active and return electrode position. The model predicts improved prosthesis performance when the reference electrode is in the labyrinth’s common crus (CC) rather than outside the temporal bone, especially if the reference electrode is inserted nearly to the junction of the CC with the vestibule. Extension of the model to human anatomy should facilitate optimal design of electrode arrays for clinical application.
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Virtual labyrinth model of Vestibular afferent excitation via implanted electrodes: validation and application to design of a multichannel Vestibular prosthesis
Experimental Brain Research, 2011Co-Authors: Russell Hayden, Stacia Sawyer, Eric Frey, Susumu Mori, Americo A. Migliaccio, Charles C. Della SantinaAbstract:To facilitate design of a multichannel Vestibular prosthesis that can restore sensation to individuals with bilateral loss of Vestibular Hair Cell function, we created a virtual labyrinth model. Model geometry was generated through 3-dimensional (3D) reconstruction of microMRI and microCT scans of normal chinchillas ( Chinchilla lanigera ) acquired with 30–48 μm and 12 μm voxels, respectively. Virtual electrodes were positioned based on anatomic landmarks, and the extraCellular potential field during a current pulse was computed using finite element methods. Potential fields then served as inputs to stochastic, nonlinear dynamic models for each of 2,415 Vestibular afferent axons with spiking dynamics based on a modified Smith and Goldberg model incorporating parameters that varied with fiber location in the neuroepithelium. Action potential propagation was implemented by a well validated model of myelinated fibers. We tested the model by comparing predicted and actual 3D angular vestibulo-ocular reflex (aVOR) axes of eye rotation elicited by prosthetic stimuli. Actual responses were measured using 3D video-oculography. The model was individualized for each animal by placing virtual electrodes based on microCT localization of real electrodes. 3D eye rotation axes were predicted from the relative proportion of model axons excited within each of the three ampullary nerves. Multiple features observed empirically were observed as emergent properties of the model, including effects of active and return electrode position, stimulus amplitude and pulse waveform shape on target fiber recruitment and stimulation selectivity. The modeling procedure is partially automated and can be readily adapted to other species, including humans.
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Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel Vestibular prosthesis
Experimental Brain Research, 2011Co-Authors: Chenkai Dai, Gene Y. Fridman, Bryce Chiang, Natan S. Davidovics, Thuy-anh Melvin, Kathleen E. Cullen, Charles C. Della SantinaAbstract:By sensing three-dimensional (3D) head rotation and electrically stimulating the three ampullary branches of a Vestibular nerve to encode head angular velocity, a multichannel Vestibular prosthesis (MVP) can restore Vestibular sensation to individuals disabled by loss of Vestibular Hair Cell function. However, current spread to afferent fibers innervating non-targeted canals and otolith end organs can distort the Vestibular nerve activation pattern, causing misalignment between the perceived and actual axis of head rotation. We hypothesized that over time, central neural mechanisms can adapt to correct this misalignment. To test this, we rendered five chinchillas Vestibular deficient via bilateral gentamicin treatment and unilaterally implanted them with a head-mounted MVP. Comparison of 3D angular vestibulo-ocular reflex (aVOR) responses during 2 Hz, 50°/s peak horizontal sinusoidal head rotations in darkness on the first, third, and seventh days of continual MVP use revealed that eye responses about the intended axis remained stable (at about 70% of the normal gain) while misalignment improved significantly by the end of 1 week of prosthetic stimulation. A comparable time course of improvement was also observed for head rotations about the other two semicircular canal axes and at every stimulus frequency examined (0.2–5 Hz). In addition, the extent of disconjugacy between the two eyes progressively improved during the same time window. These results indicate that the central nervous system rapidly adapts to multichannel prosthetic Vestibular stimulation to markedly improve 3D aVOR alignment within the first week after activation. Similar adaptive improvements are likely to occur in other species, including humans.
Junha Song - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1
2019Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Willy WriggersAbstract:Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run in parallel for long distances, 13 nm apart, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
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electron cryo tomography of Vestibular Hair Cell stereocilia
Journal of Structural Biology, 2019Co-Authors: Zoltan Metlagel, Junha Song, Jocelyn F. Krey, Mark F Swift, William J Tivol, Rachel A Dumont, Jasmine Thai, Alex Chang, Helia Seifikar, Niels VolkmannAbstract:High-resolution imaging of Hair-Cell stereocilia of the inner ear has contributed substantially to our understanding of auditory and Vestibular function. To provide three-dimensional views of the structure of stereocilia cytoskeleton and membranes, we developed a method for rapidly freezing unfixed stereocilia on electron microscopy grids, which allowed subsequent 3D imaging by electron cryo-tomography. Structures of stereocilia tips, shafts, and tapers were revealed, demonstrating that the actin paracrystal was not perfectly ordered. This sample-preparation and imaging procedure will allow for examination of structural features of stereocilia in a near-native state.
Willy Wriggers - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1
2019Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Willy WriggersAbstract:Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run in parallel for long distances, 13 nm apart, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
Jocelyn F. Krey - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1
2019Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Willy WriggersAbstract:Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run in parallel for long distances, 13 nm apart, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
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electron cryo tomography of Vestibular Hair Cell stereocilia
Journal of Structural Biology, 2019Co-Authors: Zoltan Metlagel, Junha Song, Jocelyn F. Krey, Mark F Swift, William J Tivol, Rachel A Dumont, Jasmine Thai, Alex Chang, Helia Seifikar, Niels VolkmannAbstract:High-resolution imaging of Hair-Cell stereocilia of the inner ear has contributed substantially to our understanding of auditory and Vestibular function. To provide three-dimensional views of the structure of stereocilia cytoskeleton and membranes, we developed a method for rapidly freezing unfixed stereocilia on electron microscopy grids, which allowed subsequent 3D imaging by electron cryo-tomography. Structures of stereocilia tips, shafts, and tapers were revealed, demonstrating that the actin paracrystal was not perfectly ordered. This sample-preparation and imaging procedure will allow for examination of structural features of stereocilia in a near-native state.
Zoltan Metlagel - One of the best experts on this subject based on the ideXlab platform.
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A cryo-tomography-based volumetric model of the actin core of mouse Vestibular Hair Cell stereocilia lacking plastin 1.
Journal of structural biology, 2020Co-Authors: Junha Song, Roma Patterson, Jocelyn F. Krey, Samantha Hao, Linshanshan Wang, Salim Sazzed, Julio A. Kovacs, Zoltan Metlagel, Willy WriggersAbstract:Abstract Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link is expected to anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm, and the apparent filament diameter decreased from 6.4 to 4.8 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
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electron cryo tomography of Vestibular Hair Cell stereocilia
Journal of Structural Biology, 2019Co-Authors: Zoltan Metlagel, Junha Song, Jocelyn F. Krey, Mark F Swift, William J Tivol, Rachel A Dumont, Jasmine Thai, Alex Chang, Helia Seifikar, Niels VolkmannAbstract:High-resolution imaging of Hair-Cell stereocilia of the inner ear has contributed substantially to our understanding of auditory and Vestibular function. To provide three-dimensional views of the structure of stereocilia cytoskeleton and membranes, we developed a method for rapidly freezing unfixed stereocilia on electron microscopy grids, which allowed subsequent 3D imaging by electron cryo-tomography. Structures of stereocilia tips, shafts, and tapers were revealed, demonstrating that the actin paracrystal was not perfectly ordered. This sample-preparation and imaging procedure will allow for examination of structural features of stereocilia in a near-native state.