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Neurons of the Auditory Pathways
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Neurons of the Auditory Pathways

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 20570

Special Issue Editor

Dr. Gabriela Pavlinkova

E-Mail Website
Guest Editor
Laboratory of Molecular Pathogenetics, Institute of Biotechnology CAS, BIOCEV, Center of Excellence, Prumyslova 595, 25250 Vestec, Prague-West District, Czech Republic
Interests: developmental biology inner ear; transcriptional regulation; congenital defects; genetic mutations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This research topic aims to provide deeper insights into neuronal development and the molecular requirements for maintenance and function of neurons in the auditory pathways. We encourage the submission of original research and review articles dissecting molecular aspects of auditory neuron development and auditory information processing, and designing new therapeutic strategies for possible future applications in this field.

Hearing loss is a growing problem in aged societies and is among the top 10 disabilities. Recent data suggest that the prevention of neuronal loss and enhancement of long-term maintenance of neurons are the most important targets for the immediate future. The critical step for understanding the pathophysiology of hearing disorders is to identify genes and molecular pathways that are crucial in generating auditory neurons and in processing auditory information in the brain. Despite recent scientific advances, including single cell transcriptome-based approaches, the molecular cues that specify the cellular phenotype of inner ear neurons, neurite guidance, and pathfinding are still unclear. Furthermore, how neuron dysfunction alters the central auditory pathways and overall transmission of auditory information is poorly understood.

Dr. Gabriela Pavlinkova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inner ear
  • transcription regulation
  • hearing disorders
  • gene therapy
  • profiling
  • brain plasticity

Published Papers (5 papers)

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Research

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17 pages, 3600 KiB  
Article
Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus
by Tetyana Chumak, Diana Tothova, Iva Filova, Zbynek Bures, Jiri Popelar, Gabriela Pavlinkova and Josef Syka
Int. J. Mol. Sci. 2021, 22(9), 4507; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094507 - 26 Apr 2021
Cited by 2 | Viewed by 1860
Abstract
The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter [...] Read more.
The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition. Full article
(This article belongs to the Special Issue Neurons of the Auditory Pathways)
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Review

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27 pages, 3976 KiB  
Review
Roles of Key Ion Channels and Transport Proteins in Age-Related Hearing Loss
by Parveen Bazard, Robert D. Frisina, Alejandro A. Acosta, Sneha Dasgupta, Mark A. Bauer, Xiaoxia Zhu and Bo Ding
Int. J. Mol. Sci. 2021, 22(11), 6158; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116158 - 07 Jun 2021
Cited by 12 | Viewed by 5910
Abstract
The auditory system is a fascinating sensory organ that overall, converts sound signals to electrical signals of the nervous system. Initially, sound energy is converted to mechanical energy via amplification processes in the middle ear, followed by transduction of mechanical movements of the [...] Read more.
The auditory system is a fascinating sensory organ that overall, converts sound signals to electrical signals of the nervous system. Initially, sound energy is converted to mechanical energy via amplification processes in the middle ear, followed by transduction of mechanical movements of the oval window into electrochemical signals in the cochlear hair cells, and finally, neural signals travel to the central auditory system, via the auditory division of the 8th cranial nerve. The majority of people above 60 years have some form of age-related hearing loss, also known as presbycusis. However, the biological mechanisms of presbycusis are complex and not yet fully delineated. In the present article, we highlight ion channels and transport proteins, which are integral for the proper functioning of the auditory system, facilitating the diffusion of various ions across auditory structures for signal transduction and processing. Like most other physiological systems, hearing abilities decline with age, hence, it is imperative to fully understand inner ear aging changes, so ion channel functions should be further investigated in the aging cochlea. In this review article, we discuss key various ion channels in the auditory system and how their functions change with age. Understanding the roles of ion channels in auditory processing could enhance the development of potential biotherapies for age-related hearing loss. Full article
(This article belongs to the Special Issue Neurons of the Auditory Pathways)
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21 pages, 3441 KiB  
Review
Development in the Mammalian Auditory System Depends on Transcription Factors
by Karen L. Elliott, Gabriela Pavlínková, Victor V. Chizhikov, Ebenezer N. Yamoah and Bernd Fritzsch
Int. J. Mol. Sci. 2021, 22(8), 4189; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084189 - 18 Apr 2021
Cited by 36 | Viewed by 4138
Abstract
We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear [...] Read more.
We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstream target Neurod1, to cross-regulate Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 expression for interactions with Atoh1. Upregulation of Atoh1 following Neurod1 loss changes some vestibular neurons’ fate into “hair cells”, highlighting the significant interplay between the bHLH genes. Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. The inhibition of Atoh1 by Neurod1 is essential for proper neuronal cell fate, and in the absence of Neurod1, Atoh1 is upregulated, resulting in the formation of “intraganglionic” HCs. Additional genes, such as Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b, play a role in the auditory system. Finally, both Lmx1a and Lmx1b genes are essential for the cochlear organ of Corti, spiral ganglion neuron, and cochlear nuclei formation. We integrate the mammalian auditory system development to provide comprehensive insights beyond the limited perception driven by singular investigations of cochlear neurons, cochlear hair cells, and cochlear nuclei. A detailed analysis of gene expression is needed to understand better how upstream regulators facilitate gene interactions and mammalian auditory system development. Full article
(This article belongs to the Special Issue Neurons of the Auditory Pathways)
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12 pages, 301 KiB  
Review
Growth Hormone and the Auditory Pathway: Neuromodulation and Neuroregeneration
by Joaquín Guerra Gómez and Jesús Devesa
Int. J. Mol. Sci. 2021, 22(6), 2829; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062829 - 11 Mar 2021
Cited by 1 | Viewed by 2408
Abstract
Growth hormone (GH) plays an important role in auditory development during the embryonic stage. Exogenous agents such as sound, noise, drugs or trauma, can induce the release of this hormone to perform a protective function and stimulate other mediators that protect the auditory [...] Read more.
Growth hormone (GH) plays an important role in auditory development during the embryonic stage. Exogenous agents such as sound, noise, drugs or trauma, can induce the release of this hormone to perform a protective function and stimulate other mediators that protect the auditory pathway. In addition, GH deficiency conditions hearing loss or central auditory processing disorders. There are promising animal studies that reflect a possible regenerative role when exogenous GH is used in hearing impairments, demonstrated in in vivo and in vitro studies, and also, even a few studies show beneficial effects in humans presented and substantiated in the main text, although they should not exaggerate the main conclusions. Full article
(This article belongs to the Special Issue Neurons of the Auditory Pathways)
13 pages, 2930 KiB  
Review
Molecular Aspects of the Development and Function of Auditory Neurons
by Gabriela Pavlinkova
Int. J. Mol. Sci. 2021, 22(1), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010131 - 24 Dec 2020
Cited by 8 | Viewed by 5430
Abstract
This review provides an up-to-date source of information on the primary auditory neurons or spiral ganglion neurons in the cochlea. These neurons transmit auditory information in the form of electric signals from sensory hair cells to the first auditory nuclei of the brain [...] Read more.
This review provides an up-to-date source of information on the primary auditory neurons or spiral ganglion neurons in the cochlea. These neurons transmit auditory information in the form of electric signals from sensory hair cells to the first auditory nuclei of the brain stem, the cochlear nuclei. Congenital and acquired neurosensory hearing loss affects millions of people worldwide. An increasing body of evidence suggest that the primary auditory neurons degenerate due to noise exposure and aging more readily than sensory cells, and thus, auditory neurons are a primary target for regenerative therapy. A better understanding of the development and function of these neurons is the ultimate goal for long-term maintenance, regeneration, and stem cell replacement therapy. In this review, we provide an overview of the key molecular factors responsible for the function and neurogenesis of the primary auditory neurons, as well as a brief introduction to stem cell research focused on the replacement and generation of auditory neurons. Full article
(This article belongs to the Special Issue Neurons of the Auditory Pathways)
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