scholarly journals Spontaneous and coordinated Ca2+ activity of cochlear sensory and non-sensory cells drives the maturation of OHC afferent innervation

2018 ◽  
Author(s):  
Federico Ceriani ◽  
Aenea Hendry ◽  
Jing-Yi Jeng ◽  
Stuart L. Johnson ◽  
Jennifer Olt ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Outer Hair Cells ◽  
Fine Tuning ◽  
Sensory Cells ◽  
Early Postnatal Development ◽  
Acoustic Stimuli ◽  
Ribbon Synapses ◽  
Immature Development ◽  
Afferent Innervation

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca2+ signalling in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca2+ signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca2+ spikes during a narrow period of immature development. Simultaneously, waves of Ca2+ activity in the non-sensory greater epithelial ridge act, via ATP-induced activation of P2X receptors, to synchronize OHC firing, resulting in the refinement of their afferent innervation. In the absence of connexin channels Ca2+ waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity in OHCs requires experience-independent Ca2+ signals from sensory and non-sensory cells.

scholarly journals Selective Removal of Lateral Olivocochlear Efferents Increases Vulnerability to Acute Acoustic Injury

2007 ◽  
Vol 97 (2) ◽  
pp. 1775-1785 ◽  
Author(s):  
Keith N. Darrow ◽  
Stéphane F. Maison ◽  
M. Charles Liberman
Keyword(s):  
Brain Stem ◽  
Otoacoustic Emissions ◽  
Outer Hair Cells ◽  
Cochlear Nerve ◽  
Sensory Cells ◽  
Neural Responses ◽  
Distortion Product ◽  
Auditory Brain Stem ◽  
Pharmacological Studies

Cochlear sensory cells and neurons receive efferent feedback from the olivocochlear (OC) system. The myelinated medial component of the OC system and its effects on outer hair cells (OHCs) have been implicated in protection from acoustic injury. The unmyelinated lateral (L)OC fibers target ipsilateral cochlear nerve dendrites and pharmacological studies suggest the LOC's dopaminergic component may protect these dendrites from excitotoxic effects of acoustic overexposure. Here, we explore LOC function in vivo by selective stereotaxic destruction of LOC cell bodies in mouse. Lesion success in removing the LOC, and sparing the medial (M)OC, was assessed by histological analysis of brain stem sections and cochlear whole mounts. Auditory brain stem responses (ABRs), a neural-based metric, and distortion product otoacoustic emissions (DPOAEs), an OHC-based metric, were measured in control and surgical mice. In cases where the LOC was at least partially destroyed, there were increases in suprathreshold neural responses that were frequency- and level-independent and not attributable to OHC-based effects. These interaural response asymmetries were not found in controls or in cases where the lesion missed the LOC. In LOC-lesion cases, after exposure to a traumatic stimulus, temporary threshold shifts were greater in the ipsilateral ear, but only when measured in the neural response; OHC-based measurements were always bilaterally symmetric, suggesting OHC vulnerability was unaffected. Interaural asymmetries in threshold shift were not found in either unlesioned controls or in cases that missed the LOC. These findings suggest that the LOC modulates cochlear nerve excitability and protects the cochlea from neural damage in acute acoustic injury.

Outer Hair Cells Provide Active Tuning in the Organ of Corti

Physiology ◽  
1998 ◽  
Vol 13 (3) ◽  
pp. 107-111 ◽  
Author(s):  
Mats Ulfendahl ◽  
Åke Flock
Keyword(s):  
Mechanical Behavior ◽  
Hair Cells ◽  
Organ Of Corti ◽  
High Sensitivity ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Effector Cells ◽  
Hearing Organ

The detection of sound by the mammalian hearing organ, the organ of Corti, is far from a passive process with the sensory cells acting as mere receptors. The high sensitivity and sharp tuning of the auditory apparatus are very much dependant on the active mechanical behavior of the outer hair cells, acting as effector cells.

Physiologically silent sodium channels in mammalian outer hair cells

1994 ◽  
Vol 72 (2) ◽  
pp. 1037-1040 ◽  
Author(s):  
C. M. Witt ◽  
H. Y. Hu ◽  
W. E. Brownell ◽  
D. Bertrand
Keyword(s):  
Sodium Channels ◽  
Hair Cells ◽  
Sodium Current ◽  
High Sensitivity ◽  
Outer Hair Cells ◽  
Inward Current ◽  
Cell Recording ◽  
Voltage Dependent

1. Voltage-dependent properties of isolated guinea pig outer hair cells (OHCs) were investigated using whole-cell recording. An inward current was detected in approximately 10% of the cells. This inward current was identified as belonging to the voltage-activated sodium current family on the basis of its high sensitivity to tetrodotoxin and the effect of substitution of impermeant ions. Although this is the first report of a sodium current in the mammalian cochlea, it differs from the classical neuronal sodium current by having a variable magnitude from cell to cell and an inactivation that is shifted to hyperpolarized potentials. The sensory processing role of hair cells in general and outer hair cells in particular could be disrupted by the presence of a regenerative voltage-dependent current. The functional role of the OHC sodium channels is puzzling, particularly as they may be silent in vivo.

scholarly journals Hair Cell Generation in Cochlear Culture Models Mediated by Novel γ-Secretase Inhibitors

2021 ◽  
Vol 9 ◽  
Author(s):  
Silvia T. Erni ◽  
John C. Gill ◽  
Carlotta Palaferri ◽  
Gabriella Fernandes ◽  
Michelle Buri ◽  
...  
Keyword(s):  
Hair Cell ◽  
Notch Signaling ◽  
Hair Cells ◽  
Round Window ◽  
Notch Pathway ◽  
Outer Hair Cells ◽  
Round Window Membrane ◽  
Sensory Cells ◽  
Supporting Cells

Sensorineural hearing loss is prevalent within society affecting the quality of life of 460 million worldwide. In the majority of cases, this is due to insult or degeneration of mechanosensory hair cells in the cochlea. In adult mammals, hair cell loss is irreversible as sensory cells are not replaced spontaneously. Genetic inhibition of Notch signaling had been shown to induce hair cell formation by transdifferentiation of supporting cells in young postnatal rodents and provided an impetus for targeting Notch pathway with small molecule inhibitors for hearing restoration. Here, the oto-regenerative potential of different γ-secretase inhibitors (GSIs) was evaluated in complementary assay models, including cell lines, organotypic cultures of the organ of Corti and cochlear organoids to characterize two novel GSIs (CPD3 and CPD8). GSI-treatment induced hair cell gene expression in all these models and was effective in increasing hair cell numbers, in particular outer hair cells, both in baseline conditions and in response to ototoxic damage. Hair cells were generated from transdifferentiation of supporting cells. Similar findings were obtained in cochlear organoid cultures, used for the first time to probe regeneration following sisomicin-induced damage. Finally, effective absorption of a novel GSI through the round window membrane and hair cell induction was attained in a whole cochlea culture model and in vivo pharmacokinetic comparisons of transtympanic delivery of GSIs and different vehicle formulations were successfully conducted in guinea pigs. This preclinical evaluation of targeting Notch signaling with novel GSIs illustrates methods of characterization for hearing restoration molecules, enabling translation to more complex animal studies and clinical research.

scholarly journals Coordinated calcium signalling in cochlear sensory and non‐sensory cells refines afferent innervation of outer hair cells

2019 ◽  
Vol 38 (9) ◽  
Author(s):  
Federico Ceriani ◽  
Aenea Hendry ◽  
Jing‐Yi Jeng ◽  
Stuart L Johnson ◽  
Friederike Stephani ◽  
...  
Keyword(s):  
Hair Cells ◽  
Calcium Signalling ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Afferent Innervation

A Novel Effect of Cochlear Efferents: In Vivo Response Enhancement Does Not Require α9 Cholinergic Receptors

2007 ◽  
Vol 97 (5) ◽  
pp. 3269-3278 ◽  
Author(s):  
Stéphane F. Maison ◽  
Douglas E. Vetter ◽  
M. Charles Liberman
Keyword(s):  
Otoacoustic Emissions ◽  
Feedback Loop ◽  
Outer Hair Cells ◽  
Neural Responses ◽  
Targeted Deletion ◽  
Acoustic Stimuli ◽  
Response Enhancement ◽  
Post Shock ◽  
Cholinergic Effects

Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by α9/α10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of ∼100 s. In mice with targeted deletion of the α9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported.

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

scholarly journals Optimization of spectral-domain optical coherence tomography with a supercontinuum source for in vivo motion detection of low reflective outer hair cells in guinea pig cochleae

2021 ◽  
Author(s):  
Fumiaki Nin ◽  
Samuel Choi ◽  
Takeru Ota ◽  
Zhang Qi ◽  
Hiroshi Hibino
Keyword(s):  
Optical Coherence Tomography ◽  
High Resolution ◽  
Guinea Pig ◽  
Hair Cells ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Acquisition Time ◽  
Total Acquisition Time ◽  
Sd Oct

AbstractSound evokes sub-nanoscale vibration within the sensory epithelium. The epithelium contains not only immotile cells but also contractile outer hair cells (OHCs) that actively shrink and elongate synchronously with the sound. However, the in vivo motion of OHCs has remained undetermined. The aim of this work is to perform high-resolution and -accuracy vibrometry in live guinea pigs with an SC-introduced spectral-domain optical coherence tomography system (SD-OCT). In this study, to reveal the effective contribution of SC source in the recording of the low reflective materials with the short total acquisition time, we compare the performances of the SC-introduced SD-OCT (SCSD-OCT) to that of the conventional SD-OCT. As inanimate comparison objects, we record a mirror, a piezo actuator, and glass windows. For the measurements in biological materials, we use in/ex vivo guinea pig cochleae. Our study achieved the optimization of a SD-OCT system for high-resolution in vivo vibrometry in the cochlear sensory epithelium, termed the organ of Corti, in mammalian cochlea. By introducing a supercontinuum (SC) light source and reducing the total acquisition time, we improve the axial resolution and overcome the difficulty in recording the low reflective material in the presence of biological noise. The high power of the SC source enables the system to achieve a spatial resolution of 1.72 ± 0.00 μm on a mirror and reducing the total acquisition time contributes to the high spatial accuracy of sub-nanoscale vibrometry. Our findings reveal the vibrations at the apical/basal region of OHCs and the extracellular matrix, basilar membrane.

scholarly journals Persistent luminescence nanoparticles for cancer theranostics application

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Nian Liu ◽  
Xiao Chen ◽  
Xia Sun ◽  
Xiaolian Sun ◽  
Junpeng Shi
Keyword(s):  
Uv Light ◽  
Combined Therapy ◽  
Tumor Therapy ◽  
High Sensitivity ◽  
Persistent Luminescence ◽  
Therapeutic Drugs ◽  
High Penetration ◽  
Recent Developments ◽  
Cancer Theranostics

AbstractPersistent luminescence nanoparticles (PLNPs) are unique optical materials that emit afterglow luminescence after ceasing excitation. They exhibit unexpected advantages for in vivo optical imaging of tumors, such as autofluorescence-free, high sensitivity, high penetration depth, and multiple excitation sources (UV light, LED, NIR laser, X-ray, and radiopharmaceuticals). Besides, by incorporating other functional molecules, such as photosensitizers, photothermal agents, or therapeutic drugs, PLNPs are also widely used in persistent luminescence (PersL) imaging-guided tumor therapy. In this review, we first summarize the recent developments in the synthesis and surface functionalization of PLNPs, as well as their toxicity studies. We then discuss the in vivo PersL imaging and multimodal imaging from different excitation sources. Furthermore, we highlight PLNPs-based cancer theranostics applications, such as fluorescence-guided surgery, photothermal therapy, photodynamic therapy, drug/gene delivery and combined therapy. Finally, future prospects and challenges of PLNPs in the research of translational medicine are also discussed.

scholarly journals Ubiquitylome Analysis Reveals a Central Role for the Ubiquitin-Proteasome System in Plant Innate Immunity

2021 ◽  
Author(s):  
Xiyu Ma ◽  
Chao Zhang ◽  
Do Young Kim ◽  
Yanyan Huang ◽  
Elizabeth Chatt ◽  
...  
Keyword(s):  
Plant Immunity ◽  
High Sensitivity ◽  
Ubiquitin Proteasome System ◽  
Immune Recognition ◽  
Atpase Subunit ◽  
Ample Evidence ◽  
Network Analyses ◽  
Affinity Enrichment ◽  
Regulatory Loop

Abstract Protein ubiquitylation profoundly expands proteome functionality and diversifies cellular signaling processes, with recent studies providing ample evidence for its importance to plant immunity. To gain a proteome-wide appreciation of ubiquitylome dynamics during immune recognition, we employed a two-step affinity enrichment protocol based on a 6His-tagged ubiquitin (Ub) variant coupled with high sensitivity mass spectrometry to identify Arabidopsis proteins rapidly ubiquitylated upon plant perception of the microbe-associated molecular pattern (MAMP) peptide flg22. The catalog from 2-week-old seedlings treated for 30 minutes with flg22 contained 690 conjugates, 64 Ub footprints, and all seven types of Ub linkages, and included previously uncharacterized conjugates of immune components. In vivo ubiquitylation assays confirmed modification of several candidates upon immune elicitation, and revealed distinct modification patterns and dynamics for key immune components, including poly- and monoubiquitylation, as well as induced or reduced levels of ubiquitylation. Gene ontology and network analyses of the collection also uncovered rapid modification of the Ub-proteasome system itself, suggesting a critical auto-regulatory loop necessary for an effective MAMP-triggered immune response and subsequent disease resistance. Included targets were UBIQUITIN-CONJUGATING ENZYME 13 (UBC13) and proteasome component REGULATORY PARTICLE NON-ATPASE SUBUNIT 8b (RPN8b), whose subsequent biochemical and genetic analyses implied negative roles in immune elicitation. Collectively, our proteomic analyses further strengthened the connection between ubiquitylation and flg22-based immune signaling, identified components and pathways regulating plant immunity, and increased the database of ubiquitylated substrates in plants.

Sign in / Sign up

Export Citation Format

Share Document