Review
Cell Biology
Christie Mitri, Himanshu Sharma, Harriet Corvol, Olivier Tabary
Summary: Cystic fibrosis is a common hereditary disease affecting Caucasians, with approximately 75,000 patients worldwide. Mutations in the CFTR gene cause dysfunction in the CFTR protein, and treatments include correctors and potentiators; however, alternative CFTR-independent strategies are still being explored.
Article
Multidisciplinary Sciences
Tessa R. Sanders, Matthew W. Kelley
Summary: Transcriptional analysis reveals that the afferent innervation of the cochlea goes through a process of splitting and differentiation to generate four transcriptionally distinct subtypes. The initial specification process is genetically controlled and may also be regulated by other transcription factors during subsequent development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Daniel Leon-Aparicio, Jorge Arreola, Patricia Perez-Cornejo, Alfredo Sanchez-Solano
Summary: The study shows that oleic acid irreversibly blocks the TMEM16A chloride channel in a dose- and voltage-dependent manner, possibly through an allosteric mechanism. This blockage is intensified by increasing the extracellular anion concentration and is independent of voltage for certain pore mutants.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Review
Pharmacology & Pharmacy
Yani Liu, Zongtao Liu, KeWei Wang
Summary: ANO1 gene encodes a Ca2+ activated Cl- channel critical for physiological functions, with abnormal expression or dysfunction linked to various diseases. The lack of specific modulators hinders the validation of ANO1 as a therapeutic target.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Pharmacology & Pharmacy
Luis J. Galietta
Summary: Cystic fibrosis is a genetic disease caused by the dysfunction of CFTR, a chloride channel expressed in epithelial cells. The loss of CFTR function leads to chronic bacterial infections and airway obstruction. Another chloride channel called TMEM16A may play a role in mucus hypersecretion, but further research is needed to confirm this relationship.
CURRENT OPINION IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Hui Hong, Douglas Zeppenfeld, Laurence O. Trussell
Summary: Efferent neurons, specifically the lateral olivocochlear (LOC) neurons, play vital roles in maintaining auditory function. Through in vitro experiments, it was discovered that LOC neurons in juvenile and young adult mice exhibited extremely slow waves of activity driven by an intrinsic oscillator dependent on L-type Ca2+ channels. Additionally, optogenetic approaches helped identify both ascending and descending sources of synaptic excitation, as well as the synaptic receptors involved. These findings provide important insights into the mechanisms of diverse transmitter release by LOC fibers in the cochlea.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Travis A. Babola, Sally Li, Zhirong Wang, Calvin J. Kersbergen, Ana Belen Elgoyhen, Thomas M. Coate, Dwight E. Bergles
Summary: Spontaneous bursts of electrical activity in the developing auditory system originate in the cochlea before hearing onset, with ATP release from inner supporting cells activating purinergic autoreceptors and promoting maturation of auditory neurons. Inhibition of P2Y1 purinergic receptors dramatically reduces spontaneous activity in inner hair cells, spiral ganglion neurons, and auditory neurons at all developmental ages. This consistent mechanism involving ATP release and P2Y1 activation elicits coordinated excitation of neurons processing similar frequencies of sound.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Pengmei Guo, Yu Liu, Xiaojia Xu, Guijin Ma, Xiaomin Hou, Yanying Fan, Mingsheng Zhang
Summary: The study showed that enhanced activity of CaCCs in arterial smooth muscle cells and increased Ca2+ mobilization play a pivotal role in the distinctive hypercontractility of rat coronary arteries to acidosis, which may lead to a new approach in understanding and treating cardiac complications in severe acidosis.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Neurosciences
Basile Tarchini
Summary: Sensory hair cells detect mechanical stimuli through their hair bundle structure, which determines their directional sensitivity. Coordinated orientation of same-side hair cells ensures the delivery of local group response, while the differential orientation of opposite-side hair cells provides bidirectional sensitivity at the organ level.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
German Nacher-Soler, Sebastien Lenglet, Marta Coelho, Aurelien Thomas, Francois Voruz, Karl-Heinz Krause, Pascal Senn, Francis Rousset
Summary: Cisplatin is an important chemotherapeutic drug with significant ototoxicity, leading to hearing loss in cancer-surviving patients. A local delivery model of cisplatin offers a reliable way to induce hearing loss with minimal morbidity in rodents, reducing the number of animals needed for ototoxicity studies while improving animal welfare compared to systemic models.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Karen L. Elliott, Gabriela Pavlinkova, Victor V. Chizhikov, Ebenezer N. Yamoah, Bernd Fritzsch
Summary: The article presents a molecular review of transcription factors involved in the development of spiral ganglia, cochlear nuclei, and cochlear hair cells, emphasizing the interactions between Neurog1, Neurod1, and Atoh1. It highlights the significant interplay between bHLH genes and their potential to partially replace one another. Additionally, other genes such as Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b play vital roles in the auditory system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell & Tissue Engineering
Hiroki Takeda, Anna Dondzillo, Jessica A. Randall, Samuel P. Gubbels
Summary: The study demonstrates the feasibility of human stem cell engraftment into an ablated mouse organ of Corti, showing increased engraftment and differentiation of transplanted cells into hair and supporting cell immunophenotypes after hair cell ablation prior to transplantation.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Neurosciences
Nicholas S. Andresen, Sarah Coreas, Dillan F. Villavisanis, Amanda M. Lauer
Summary: This research examined the pigmentation within temporal bones of mice and humans, revealing an increase in melanin within the stria vascularis with age, but not within the vestibular system. African-American individuals showed higher levels of pigment within the SV and vestibular system in both pediatric and adult populations.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Audiology & Speech-Language Pathology
Connie B. Paik, Michelle Pei, John S. Oghalai
Summary: The article comprehensively reviews blast-related auditory pathology and discusses mechanistic studies on molecular and microstructural events. Key findings include the association between endolymphatic hydrops and cochlear synaptic loss, as well as blast-induced neuroinflammatory markers in the peripheral and central auditory system. Blast causes cochlear damage similar to, but more severe than, standard noise exposure.
Article
Respiratory System
Hayley Pearson, Eleanor J. A. A. Todd, Mareike Ahrends, Samantha E. Hover, Adrian Whitehouse, Martin Stacey, Jonathan D. Lippiat, Ludwig Wilkens, Hans-Gerd Fieguth, Olga Danov, Christina Hesse, John N. Barr, Jamel Mankouri
Summary: HRSV is a common cause of respiratory infections globally, particularly fatal for infants. Research has identified the TMEM16A channel as crucial for HRSV infection, suggesting it as a potential target for future antiviral therapies.
Article
Chemistry, Multidisciplinary
Aida Garrido-Charles, Antoine Huet, Carlo Matera, Anupriya Thirumalai, Jordi Hernando, Amadeu Llebaria, Tobias Moser, Pau Gorostiza
Summary: Artificial control of neuronal activity is crucial for studying neural circuits and restoring neural functions. In this study, researchers developed fast photoswitchable ligands of glutamate receptors (GluRs) to enable direct and reversible control of intact neurons using visible light pulses. These new photoswitchable ligands successfully induced photocurrents in untransfected auditory neurons, offering a drug-based approach for optical stimulation without the need for genetic manipulation. This method shows potential for spatiotemporal control of neural activities in the brain.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
A. Calapai, J. Cabrera-Moreno, T. Moser, M. Jeschke
Summary: This study presents a cage-based standalone platform for cognitive and psychoacoustic assessment of common marmosets. Through a series of experiments, it is found that the marmosets can autonomously learn to associate sounds with images, discriminate sounds flexibly, and detect sounds of varying loudness. This training method does not require dietary restriction or social separation.
NATURE COMMUNICATIONS
(2022)
Review
Medicine, Research & Experimental
Bettina Julia Wolf, Kathrin Kusch, Victoria Hunniford, Barbara Vona, Robert Kuhler, Daniel Keppeler, Nicola Strenzke, Tobias Moser
Summary: Hearing impairment is a common sensory deficit affecting millions of people worldwide, and there is a lack of effective treatment. Collaboration with cochlear implant users and the development of new therapies offer potential solutions for improving hearing restoration. Gene therapy and major innovations in cochlear implants are likely to be clinically translated within this decade.
EMBO MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Chad P. Grabner, Isabelle Jansen, Jakob Neef, Tobias Weihs, Roman Schmidt, Dietmar Riedel, Christian A. Wurm, Tobias Moser
Summary: Cells assemble macromolecular complexes into scaffoldings that serve as substrates for catalytic processes, and neurotransmission depends on such optimization strategies. This study implemented MINFLUX optical nanoscopy to visualize the molecular topography of the presynaptic active zone in rod photoreceptors.
Article
Anatomy & Morphology
Homero L. Cantu-Guerra, Michael R. Papazian, Anna L. Gorsky, Nathalie S. Alekos, Adam Caccavano, Nare Karagulyan, Jakob Neef, Stefano Vicini, Tobias Moser, Thomas M. Coate
Summary: SEMA3A may regulate the excitability of SGNs in the cochlea, which could influence the morphology and synaptic arrangement of type I SGNs.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Clinical Neurology
Artur Mittring, Tobias Moser, Antoine Tarquin Huet
Summary: Optogenetic control allows for innovative approaches to restore function in diseased sensory and motor systems. Customization of channelrhodopsins, emitters, and coding strategies is necessary to achieve success in clinical translation. This study provides a framework for parametrizing optogenetic neural control and applies it to the auditory pathway.
Article
Chemistry, Physical
Christian Helke, Markus Reinhardt, Markus Arnold, Falk Schwenzer, Micha Haase, Matthias Wachs, Christian Gossler, Jonathan Goetz, Daniel Keppeler, Bettina Wolf, Jannis Schaeper, Tim Salditt, Tobias Moser, Ulrich Theodor Schwarz, Danny Reuter
Summary: Improved hearing restoration through optical cochlear implants, which excite optogenetically modified spiral ganglion neurons via an optical pulse, is achieved by using flexible polymer-based waveguide probes. These probes are fabricated using micromachining processes and are capable of guiding light with low intensity loss.
Article
Neurosciences
Victoria Hunniford, Robert Kuehler, Bettina Wolf, Daniel Keppeler, Nicola Strenzke, Tobias Moser
Summary: Hearing-impaired individuals using electrical cochlear implants (eCIs) expressed a desire for improved speech comprehension, music appreciation, and more natural sound impression. They showed willingness to engage with new technologies for improved hearing restoration. However, they had concerns about receiving an implant that had not been evaluated in a human clinical trial.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
H. Vitzthum, M. Koch, L. Eckermann, S. L. Svendsen, P. Berg, C. A. Huebner, C. A. Wagner, J. Leipziger, C. Meyer-Schwesinger, H. Ehmke
Summary: Maintaining acid-base balance is important for the kidneys, and the solute transporter AE4 in beta-intercalated cells is found to play a role in renal acid-base sensing mechanism.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Maria Zerche, Christian Wrobel, Kathrin Kusch, Tobias Moser, Thomas Mager
Summary: Optogenetic neurostimulation, using f-Chrimson-TSKir2.1 as a candidate, shows promise for sensory restoration and can be a potential alternative to electrical stimulation methods. Although removing the C-terminal fluorescent protein leads to a reduction in photocurrent amplitude, adjusting the dose of the adenoassociated virus vector and using the Kir2.1 trafficking sequence can restore optogenetic stimulation efficacy with minimal neural loss after a few months. This research holds significance for the clinical translation of optogenetic neurostimulation, particularly in the development of optical cochlear implants.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Review
Biochemistry & Molecular Biology
Tobias Moser, Nare Karagulyan, Jakob Neef, Lina Maria Jaime Tobon
Summary: This review discusses the mechanisms behind processing different sound pressures and intensities in the auditory system, as well as the neural decomposition and coding of sound intensity information.
Article
Biochemistry & Molecular Biology
Susann Michanski, Rohan Kapoor, Anna M. Steyer, Wiebke Moebius, Iris Frueholz, Frauke Ackermann, Mehmet Gueltas, Craig C. Garner, F. Kent Hamra, Jakob Neef, Nicola Strenzke, Tobias Moser, Carolin Wichmann
Summary: In this study, the role of piccolino in the structure and function of inner hair cell synapses was investigated using piccolo gene-trap mutant rats. The findings suggest that piccolino is essential for normal hearing and contributes to the organization of the active zone in inner hair cells.
Review
Multidisciplinary Sciences
Lakshay Khurana, Tamas Harczos, Tobias Moser, Lukasz Jablonski
Summary: Hearing loss is a common sensory deficit, and optical cochlear implants have the potential to overcome the limitations of electrical implants by using light stimulation.
