Development Of Auditory System Research Articles

8490 The mRNA for the Nonsyndromic Deafness Gene Atp2b2 Is Reduced Following Developmental Hypothyroidism

Abstract Disclosure: E.A. Gregersen: None. R.P. Peeters: None. D. Forrest: None. D.S. Sharlin: None. Thyroid hormone (TH) is essential for auditory system development. In rodent models, low levels of TH during the early postnatal period delay cochlear tissue remodeling and alter ion channel function required for normal auditory function. TH receptors are ligand-dependent transcription factors that regulate gene expression. Considering this, auditory deficits observed in hypothyroidism are thought to be largely the result of altered expression of specific TH target genes. However, few TH-regulated genes in the developing cochlea have been reported. TH is reported to impact calcium signaling in several tissues, but whether regulators of calcium signaling are altered following developmental hypothyroidism in the cochlea is largely unexplored. In this report, we investigated the spatial and temporal expression of the ATPase, Ca++ transporting, plasma membrane 2 (Atp2b2) gene in a mouse model of developmental hypothyroidism. Timed-pregnant dams were treated with thyroid gland inhibitors to induce developmental TH insufficiency from embryonic day 12.5 (E12.5) through post-natal day 15 (P15). Untreated timed-pregnant dams served as euthyroid controls. Control and experimental cochleae were collected over a developmental period ranging from embryonic day 18.5 (E18.5) through P15. Cochleae were then processed to detect Atp2b2 mRNA by in situ hybridization or quantitative real-time PCR. In situ hybridization showed that Atp2b2 localizes to inner and outer hair cells as expected, but Atp2b2 was also observed at lower levels in the greater epithelial ridge and spiral ganglion. Quantification of Atp2b2 mRNA revealed an effect of postnatal day and treatment on Atp2b2. In euthyroid animals, Atp2b2 expression gradually increased until P10, then decreased slightly by P15. In hypothyroid animals, Atp2b2 mRNA was consistently decreased (2-2.5 fold). Hypothyroidism similarly impacted expression regardless of sex. The reduction in Atp2b2 mRNA expression in the hypothyroid animals suggests that Atp2b2 is developmentally regulated in part by thyroid hormone signaling. This study characterizes the relationship between TH and Atp2b2 expression during early cochlear development while providing insight into abnormal cochlear development due to hypothyroidism. Presentation: 6/3/2024

CHD7 and SOX2 act in a common gene regulatory network during mammalian semicircular canal and cochlear development

Inner ear morphogenesis requires tightly regulated epigenetic and transcriptional control of gene expression. CHD7, an ATP-dependent chromodomain helicase DNA-binding protein, and SOX2, an SRY-related HMG box pioneer transcription factor, are known to contribute to vestibular and auditory system development, but their genetic interactions in the ear have not been explored. Here, we analyzed inner ear development and the transcriptional regulatory landscapes in mice with variable dosages of Chd7 and/or Sox2. We show that combined haploinsufficiency for Chd7 and Sox2 results in reduced otic cell proliferation, severe malformations of semicircular canals, and shortened cochleae with ectopic hair cells. Examination of mice with conditional, inducible Chd7 loss by Sox2CreER reveals a critical period (~E9.5) of susceptibility in the inner ear to combined Chd7 and Sox2 loss. Data from genome-wide RNA-sequencing and CUT&Tag studies in the otocyst show that CHD7 regulates Sox2 expression and acts early in a gene regulatory network to control expression of key otic patterning genes, including Pax2 and Otx2. CHD7 and SOX2 directly bind independently and cooperatively at transcription start sites and enhancers to regulate otic progenitor cell gene expression. Together, our findings reveal essential roles for Chd7 and Sox2 in early inner ear development and may be applicable for syndromic and other forms of hearing or balance disorders.

Harmony in the Molecular Orchestra of Hearing: Developmental Mechanisms from the Ear to the Brain.

Auditory processing in mammals begins in the peripheral inner ear and extends to the auditory cortex. Sound is transduced from mechanical stimuli into electrochemical signals of hair cells, which relay auditory information via the primary auditory neurons to cochlear nuclei. Information is subsequently processed in the superior olivary complex, lateral lemniscus, and inferior colliculus and projects to the auditory cortex via the medial geniculate body in the thalamus. Recent advances have provided valuable insights into the development and functioning of auditory structures, complementing our understanding of the physiological mechanisms underlying auditory processing. This comprehensive review explores the genetic mechanisms required for auditory system development from the peripheral cochlea to the auditory cortex. We highlight transcription factors and other genes with key recurring and interacting roles in guiding auditory system development and organization. Understanding these gene regulatory networks holds promise for developing novel therapeutic strategies for hearing disorders, benefiting millions globally.

Metabonomics and Transcriptomics Analyses Reveal the Development Process of the Auditory System in the Embryonic Development Period of the Small Yellow Croaker under Background Noise.

Underwater noise pollution has become a potential threat to aquatic animals in the natural environment. The main causes of such pollution are frequent human activities creating underwater environmental noise, including commercial shipping, offshore energy platforms, scientific exploration activities, etc. However, in aquaculture environments, underwater noise pollution has also become an unavoidable problem due to background noise created by aquaculture equipment. Some research has shown that certain fish show adaptability to noise over a period of time. This could be due to fish's special auditory organ, i.e., their "inner ear"; meanwhile, otoliths and sensory hair cells are the important components of the inner ear and are also essential for the function of the auditory system. Recently, research in respect of underwater noise pollution has mainly focused on adult fish, and there is a lack of the research on the effects of underwater noise pollution on the development process of the auditory system in the embryonic development period. Thus, in this study, we collected embryo-larval samples of the small yellow croaker (Larimichthys polyactis) in four important stages of otic vesicle development through artificial breeding. Then, we used metabonomics and transcriptomics analyses to reveal the development process of the auditory system in the embryonic development period under background noise (indoor and underwater environment sound). Finally, we identified 4026 differentially expressed genes (DEGs) and 672 differential metabolites (DMs), including 37 DEGs associated with the auditory system, and many differences mainly existed in the neurula stage (20 h of post-fertilization/20 HPF). We also inferred the regulatory mode and process of some important DEGs (Dnmt1, CPS1, and endothelin-1) in the early development of the auditory system. In conclusion, we suggest that the auditory system development of L. polyactis begins at least in the neurula stage or earlier; the other three stages (tail bud stage, caudal fin fold stage, and heart pulsation stage, 28-35 HPF) mark the rapid development period. We speculate that the effect of underwater noise pollution on the embryo-larval stage probably begins even earlier.

Development and Human Factors Evaluation of a Portable Auditory Localization Training System.

To design and develop a Portable Auditory Localization Acclimation Training (PALAT) system capable of producing psychoacoustically accurate localization cues; evaluate the training effect against a proven full-scale, laboratory-grade system under three listening conditions; and determine if the PALAT system is sensitive to differences among electronic level-dependent hearing protection devices (HPDs). In-laboratory auditory localization training has demonstrated the ability to improve localization performance with the open (natural) ear, that is, unoccluded, and while wearing HPDs. The military requires a portable system capable of imparting similar training benefits as those demonstrated in laboratory experiments. In a full-factorial repeated measures design experiment, 12 audiometrically normal participants completed localization training and testing using an identical, optimized training protocol on two training systems under three listening conditions (open ear, TEP-100, and ComTac™ III). Statistical tests were performed on mean absolute accuracy score and front-back reversal errors. No statistical difference existed between the PALAT and laboratory-grade DRILCOM systems on two dependent localization accuracy measurements at all stages of training. In addition, the PALAT system detected the same localization performance differences among the three listening conditions. The PALAT system imparted similar training benefits as the DRILCOM system and was sensitive to HPD localization performance differences. The user-operable PALAT system and optimized training protocol can be employed by the military, law enforcement, and various industries, to improve auditory localization performance in conditions where auditory situation awareness is critical to safety.

Impact of Prematurity on Auditory Processing in Children.

Prematurity is one of the most crucial risk factors negatively affecting the maturation of the auditory system. Children born preterm demonstrate high rates of hearing impairments. Auditory processing difficulties in preterm children might be a result of disturbances in the central auditory system development and/or sensory deprivation due to peripheral hearing loss. To investigate auditory processing in preterm children, we utilized a set of psychoacoustic tests to assess temporal processing and speech intelligibility. A total of 241 children aged 6-11 years old (136 born preterm and 105 healthy full-term children forming the control group) were assessed. The preterm children were divided into three groups based on their peripheral hearing status: 74 normal hearing (NH group); 30 children with bilateral permanent sensorineural hearing loss (SNHL group) and 32 children with bilateral auditory neuropathy spectrum disorder (ANSD group). The results showed significantly worse performance in all tests in premature children compared with full-term children. NH and SNHL groups showed significant age-related improvement in speech recognition thresholds in noise that might signify a "bottom-up" auditory processing maturation effect. Overall, all premature children had signs of auditory processing disorders of varying degrees. Analyzing and understanding the auditory processing specificity in preterm children can positively contribute to the more effective implementation of rehabilitation programs.

Рsychoacoustic testing to assess the functional maturation of the central audiotory system

The age-appropriate development of the central auditory system is crucial for a child’s normal auditory and speech development. If there are any issues with this development, it can lead to central auditory processing disorders (APD) and problems with psychoverbal and general development. Psychoacoustic testing is an informative and accessible diagnostic tool for identifying signs of APD. This testing can be performed on children as young as four years old, provided there are normative data available for different age groups. The purpose of this study was to assess the functional state of the central auditory system using psychoacoustic methods in healthy children of different ages. Materials Methods. We examined 125 healthy full-term children between the ages of 4 and 17 years who had normal peripheral hearing and no speech, language, cognitive, or academic problems. The children were divided into five age groups: 4–5 years 11 months, 6–7 years 11 months, 8–9 years 11 months, 10–11 years 11 months, and 12 years and older. In addition to traditional audiological examinations, all children underwent tests to assess the functional state of the central parts of the auditory system, including tests for the perception of rhythmic sequences of stimuli, Random Gap Detection Test, monaural low redundant speech testing in quiet and in noise, alternating binaural speech testing, dichotic digits test, and a simplified version of the Russian matrix sentence test in noise (RUMatrix). The results showed that the tests used were sensitive to the functional state of various structures of the central auditory system, and signs of maturation in the “bottom-up” direction were demonstrated as the children grew older. The rate of evolutionary processes varied depending on the age group of the subjects. It was also shown that the morphofunctional development of the central auditory system is not completed by adolescence. Conclusion. These findings can be used to differentiate between the immaturity of the central auditory system, APD, and speech-language disorders of different types in children of different ages. Overall, this study emphasizes the importance of early detection and intervention for any issues related to the central auditory system in children.

Neuroanatomical Disposition, Natural Development, and Training-Induced Plasticity of the Human Auditory System from Childhood to Adulthood: A 12-Year Study in Musicians and Nonmusicians.

Auditory perception is fundamental to human development and communication. However, no long-term studies have been performed on the plasticity of the auditory system as a function of musical training from childhood to adulthood. The long-term interplay between developmental and training-induced neuroplasticity of auditory processing is still unknown. We present results from AMseL (Audio and Neuroplasticity of Musical Learning), the first longitudinal study on the development of the human auditory system from primary school age until late adolescence. This 12-year project combined neurologic and behavioral methods including structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory tests. A cohort of 112 typically developing participants (51 male, 61 female), classified as "musicians" (n = 66) and "nonmusicians" (n = 46), was tested at five measurement timepoints. We found substantial, stable differences in the morphology of auditory cortex (AC) between musicians and nonmusicians even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. Maturational plasticity led to a continuous increase in white matter myelination and systematic changes of the auditory evoked P1-N1-P2 complex (decreasing latencies, synchronization effects between hemispheres, and amplitude changes) regardless of musical expertise. Musicians showed substantial training-related changes at the neurofunctional level, in particular more synchronized P1 responses and bilaterally larger P2 amplitudes. Musical training had a positive influence on elementary auditory perception (frequency, tone duration, onset ramp) and pattern recognition (rhythm, subjective pitch). The observed interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.Significance Statement We present results from AMseL (Audio and Neuroplasticity of Musical Learning), a 12-year longitudinal study on the development of the human auditory system from childhood to adulthood that combined structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory discrimination and pattern recognition tests. A total of 66 musicians and 46 nonmusicians were tested at five timepoints. Substantial, stable differences in the morphology of auditory cortex (AC) were found between the two groups even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. We also observed neuroplastic and perceptual changes with age and musical practice. This interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.

The Development of Speaking and Singing in Infants May Play a Role in Genomics and Dementia in Humans.

The development of the central auditory system, including the auditory cortex and other areas involved in processing sound, is shaped by genetic and environmental factors, enabling infants to learn how to speak. Before explaining hearing in humans, a short overview of auditory dysfunction is provided. Environmental factors such as exposure to sound and language can impact the development and function of the auditory system sound processing, including discerning in speech perception, singing, and language processing. Infants can hear before birth, and sound exposure sculpts their developing auditory system structure and functions. Exposing infants to singing and speaking can support their auditory and language development. In aging humans, the hippocampus and auditory nuclear centers are affected by neurodegenerative diseases such as Alzheimer's, resulting in memory and auditory processing difficulties. As the disease progresses, overt auditory nuclear center damage occurs, leading to problems in processing auditory information. In conclusion, combined memory and auditory processing difficulties significantly impact people's ability to communicate and engage with their societal essence.

Exposure to the persistent organic pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) disrupts development of the zebrafish inner ear

Dioxins are a class of highly toxic and persistent environmental pollutants that have been shown through epidemiological and laboratory-based studies to act as developmental teratogens. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxin congener, has a high affinity for the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. TCDD-induced AHR activation during development impairs nervous system, cardiac, and craniofacial development. Despite the robust phenotypes previously reported, the characterization of developmental malformations and our understanding of the molecular targets mediating TCDD-induced developmental toxicity remains limited. In zebrafish, TCDD-induced craniofacial malformations are produced, in part, by the downregulation of SRY-box transcription factor 9b (sox9b), a member of the SoxE gene family. sox9b, along with fellow SoxE gene family members sox9a and sox10, have important functions in the development of the otic placode, the otic vesicle, and, ultimately, the inner ear. Given that sox9b is a known target of TCDD and that transcriptional interactions exist among SoxE genes, we asked whether TCDD exposure impaired the development of the zebrafish auditory system, specifically the otic vesicle, which gives rise to the sensory components of the inner ear. Using immunohistochemistry, in vivo confocal imaging, and time-lapse microscopy, we assessed the impact of TCDD exposure on zebrafish otic vesicle development. We found exposure resulted in structural deficits, including incomplete pillar fusion and altered pillar topography, leading to defective semicircular canal development. The observed structural deficits were accompanied by reduced collagen type II expression in the ear. Together, our findings reveal the otic vesicle as a novel target of TCDD-induced toxicity, suggest that the function of multiple SoxE genes may be affected by TCDD exposure, and provide insight into how environmental contaminants contribute to congenital malformations.

Comparing Auditory Brain Stem Responses and Transient Otoacoustic Emissions in Premature Infants with Auditory Developmental Delay: Evidence of Temporary Auditory Neuropathy.

Premature birth causes some permanent or temporary abnormalities in the hearing system of the newborn. Inadequate development of the central auditory nervous system and balance, as well as the delay in the formation of the nerve myelin, can be the cause of many hearing disorders, including permanent or temporary auditory neuropathy spectrum disorder (ANSD). The present study aims to identify and understand developmental delay disorder in the hearing system of infants and investigate the possibility of temporary auditory neuropathy in infants. In this comparative analytical study, twenty premature infants were randomly selected for hearing tests using auditory brainstem response and transient otoacoustic emissions at the time of discharge and three months after the first evaluation. The different components of these tests were analyzed and compared before and after developing the auditory system. The OAEs test showed a signal-to-noise ratio above six dB with appropriate amplitudes in all infants. The grand average waveform of the ABR showed a significant difference between the amplitudes of waves III and V before and after maturation in both ears (p<0.05). In addition, the absolute latency of waves, specifically III and V, showed a significant difference between the two assessment times (0.05). The present study confirmed the occurrence of temporary ANSD or delayed maturation in premature infants following the lack of complete growth and myelination of auditory nerve fibers. There is a need to determine the hearing status of premature infants by frequent examinations and prevent any unnecessary prescription of amplifications.

Impact of unilateral hearing loss in early development.

The purpose of this review is to provide an update on current literature as it relates to the impact of unilateral hearing loss for the pediatric population. Current studies further corroborate past research findings which reveal the potential consequences of unilateral hearing loss on spatial hearing, language, and neurocognitive functioning. Deficits among children with unilateral hearing loss may parallel those seen in children with bilateral hearing loss, further challenging historic views that hearing in one ear in childhood is sufficient for normal development. The potential deficiencies seen in children with unilateral hearing loss can be subtler than those seen with bilateral hearing loss, but may nonetheless also impact school performance, patient fatigue, parental stress, and quality of life. Early interventions within a sensitive period of development of the central auditory system may circumvent potential barriers in cognitive, academic, and psychosocial development. This review synthesizes the latest research on the impact of unilateral hearing loss in childhood and the role for possible interventions. The summarized information may serve to support the development of new guidelines for the evaluation and treatment of children with unilateral hearing loss.

The distribution pattern of M2 and Adrenergicα2 receptors on inferior colliculi in male newborns of diabetic rats

AimsDespite the high prevalence of diabetes in the world, its possible effects throughut pregnancy on neonatal auditory nervous system development are still unknown. In the present research, maternal diabetes’ impact on the M2 and Adrenergicα2 receptors expression in the inferior colliculus (IC) of male newborn rats was investigated. Main MethodsFemale rats were grouped into three: sham, insulin-treated diabetic, and diabetic. Diabetes was induced through streptozotocin (STZ) injection as one dose intraperitoneally (65 mg/kg). After mating and delivery, male rats were euthanized on P0, P7, and P14. Immunohistochemistry (IHC) was used to study the distribution pattern of receptors. Key FindingsThe present study indicated that the expression of M2 receptors in the diabetic group was significantly increased in pairwise comparisons in the sham and diabetic treated with insulin groups (P < 0.001, each). The highest M2 expression was for the diabetic group on P14 and the lowest one was for the sham group on P0. The Adrenergicα2a receptors expression in the diabetic group was significantly reduced in pairwise comparisons in the sham and diabetic treated with insulin groups (P < 0.001, each). The highest Adrenergicα2a expression was for the sham group on P14 and the lowest one was for the diabetic group on P0. There was no significant difference between the sham and insulin groups regarding all receptors expression. SignificanceThis study demonstrated a time-dependent significant decrease in Adrenergicα2a but a time-dependent significant increase in M2 receptors expression.

Eph and ephrin signaling in the development of the central auditory system.

Acoustic communication relies crucially on accurate interpretation of information about the intensity, frequency, timing, and location of diverse sound stimuli in the environment. To meet this demand, neurons along different levels of the auditory system form precisely organized neural circuits. The assembly of these precise circuits requires tight regulation and coordination of multiple developmental processes. Several groups of axon guidance molecules have proven critical in controlling these processes. Among them, the family of Eph receptors and their ephrin ligands emerge as one group of key players. They mediate diverse functions at multiple levels of the auditory pathway, including axon guidance and targeting, topographic map formation, as well as cell migration and tissue pattern formation. Here, we review our current knowledge of how Eph and ephrin molecules regulate different processes in the development and maturation of central auditory circuits.

Dnmt1 is required for the development of auditory organs via cell cycle arrest and Fgf signalling.

ObjectivesTo explore the role of DNA methyltransferase 1 (DNMT1) in the development of auditory system using zebrafish as experimental model.MethodsMorpholino oligonucleotide was used to induce Dnmt1 deficiency. RNA sequencing, in situ hybridization (ISH), whole genomic bisulfide sequencing (WGBS) and immunostaining were used to investigate the morphologic alterations and mechanisms.ResultsWe found that downregulation of Dnmt1 induced decreased number of neuromasts and repressed cell proliferation of primordium in the developing posterior lateral line system of zebrafish. The ISH data uncovered that Fgf signalling pathway was inhibited and the expression of chemokine members cxcr4b, cxcr7b and cxcl12a were interfered, while lef1 expression was increased after inhibiting Dnmt1. Additionally, Dnmt1 downregulation led to malformed otoliths and deformed semicircular canals, and hair cell differentiation in utricle and saccule was inhibited severely. The in situ staining of otic placode markers pax2/5 and fgf 3/8/10 was decreased when Dnmt1 downregulated. The WGBS analysis demonstrated that the global methylation status was markedly downregulated, and cell cycle genes were among those most differently expressed between Dnmt1 morphants and the controls. Further ISH analysis confirmed the findings by RNA‐seq and WGBS assay that cdkn1a and tp53 were both upregulated after knockdown of Dnmt1.ConclusionOur results revealed that Dnmt1 is essential for the development of zebrafish auditory organ through regulating cell cycle genes together with Wnt and Fgf signalling pathways.

Kif15 Is Required in the Development of Auditory System Using Zebrafish as a Model.

Kif15, a kinesin family member, is powerful in the formation of bipolar spindles. There is emerging evidence indicating that Kif15 plays vital roles in influencing the growth of axons and interference with the progression of the tumor. However, the function of Kif15 in the auditory organs remains unknown. The Western blotting test was used to examine the effect of Kif15 downregulation by specific morpholino targeting Kif15 (Kif15-MO). The development of the inner ear and posterior lateral line (PLL) system in zebrafish was under continuous observation from spawns to 96 h postfertilization (hpf) to investigate the potential role of Kif15 in the auditory and vestibular system. We uncovered that Kif15 inhibition induced otic organ deformities in zebrafish, including malformed semicircular canals, abnormal number and location of otoliths, and reduced number of hair cells (HCs) both in utricle and saccule. Furthermore, a remarkable reduction in the number of PLL neuromasts was also explored in Kif15-MO morphants compared to the normal larvae. We also detected notably reduced activity in locomotion after Kif15 was knocked down. Additionally, we performed rescue experiments with co-injection of Kif15 mRNA and found that the Kif15 splicing MO-induced deformities in otic vesicle and PLL of zebrafish were successfully rescued, and the severely reduced locomotor activity caused by Kif15-MO was partially rescued compared to the control-MO (Con-MO) embryos. Our findings uncover that Kif15 is essential in the early development of auditory and vestibular organs using zebrafish as models.

Auditory temporal processinzg in children with history of recurrent otitis media with effusion

Objective Several studies report that a history of recurrent otitis media with effusion (OME) can affect the development of the central auditory system and its processing. The aim of the present study was to determine the effects of recurrent OME on the auditory temporal processing using the Gap-In-Noise (GIN) test in children with a positive history in their first five years. Materials and methods In this study, 12 children between 8 and 10 years old were selected. The control group was matched according to the age of study cohort. The GIN test was conducted to assess temporal processing and the approximate threshold and percentage of correct responses were calculated for all participants. Nonparametric test was used to analyze the data. Result Results of the GIN test showed significant differences between the OME and control group (p < .001). Children with recurrent OME performed worse than the control group in this test. No significant difference was observed between the right and left ear performance in both groups (p > .05). Conclusion The study results indicate that, children with recurrent OME suffer from auditory temporal processing to some degree.

GENETIC FOUNDATIONS OF THE INDIVIDUAL’S MUSICAL ABILITIES DEVELOPMENT

The article presents an overview of available foreign publications on the genetics of musicality, which is a new direction of modern science (see list of references). It is emphasized that national psychologists define the following components of musicality structure: emotional response to music as its center; the sense of rhythm; the sense of mode, and musical auditory perceptions. At the same time, foreign scholars consider musical pitch, the sense of rhythm, and the ability to experience the pleasure of music as the criteria of musicality. Foreign researchers have linked 36 genes and 7 chromosome regions with those traits. Thus, the genes AVPR1, GALM, GATA2, PCDH7, SLC6A4, and chromosome regions 4q22, 4q23, and 8q13-21 with still unidentified genes correlate most closely with musicality (Szyfter &amp; Witt, 2020). Among the above-mentioned genes, genes GATA2 and PCDH7 are involved in the auditory system development and functioning. Genes SLC6A4, and AVPR1 are responsible for getting pleasure from music, and GALM conducts carbohydrate metabolism. According to Tan, McPherson, Peretz, Berkovic &amp; Wilson, the standard expression of TRPA1 (8q21.11) provides absolute pitch and a sense of rhythm (2014). However, absolute pitch is typical only for 1-2% of professional musicians, which gives reason to doubt it is necessary to achieve a musical career (Jobling, 2014).&#x0D; The authors suggest that further research on the genetics of musicality should be based on the technology of broad genome associations research. Its value is not determined by the genes involved in musicality identification but by distinguishing the minor structural variations in the DNA molecule. These variations can alter the functioning of relevant genes in a wide range and, thus, vary the level of general musicality or special musical abilities. The identified set of genetic variations will serve as a marker for early diagnosis of musically-gifted children to ensure their successful education, upbringing, and development in the process of mandatory and regular musical and practical activities.

Encoding of fundamental frequency and fine structure of speech sounds: A comparison between adults and newborns

Encoding changes of voice pitch and formant structure plays an important role in speech comprehension since birth. Thus, proper functional assessment in perinatal hospital settings is of essence, but time constraints render the evaluation unfeasible. Here we present a novel two-vowel, rising-pitch-ending stimulus (/oa/; 250 ms) to analyze pitch tracking and low-frequency formant encoding accuracy simultaneously in approximately 30s, extracting measurements from the Frequency-Following Response (FFR) auditory evoked potential recorded with clinical hardware developed for audiology assessments. Thirty-four healthy newborns (mean gestational age = 40 week) and 18 normal-hearing adults were tested. Results showed significant differences across groups in neural lag and F0 spectral amplitude, but not in F0 signal-to-noise ratio, stimulus-to-response correlation or pitch measures, indicating that newborns and adults are able to track F0 changes accurately. FFR’s fine-structure analyses revealed that adults encode formant structure of vowels significantly better than newborns, with largest differences at high-frequency ranges. Here, we demonstrate the feasibility to assess speech envelope and fine-structure encoding within clinical evaluation times in a hospital setting. Our results indicate that voice pitch encoding is adult-like at birth, while formant representation is maturing at birth, suggesting the possibility to use this new stimulus as a measure of auditory system development in newborns.

CRISPR/Cas9-mediated pou4f3 knockout induces defects in the development of the zebrafish inner ear

Abstract Objective: The zebrafish is an excellent model for studying gene function in auditory system development. Pou4f3 plays an important role in mouse hair cell formation. Here, we constructed a pou4f3-knockout Tg(Brn3c:GFP) zebrafish to provide an efficient fluorescence-visualized model for studying the molecular mechanisms of ear development. Methods: Cas9/single guide RNAs targeting exon 2 of pou4f3 were designed and injected into one-cell stage zebrafish embryos (G0 generation). The G0 generation were crossed with Tg(Brn3c:GFP) zebrafish to obtain pou4f3-mutant Tg(Brn3c:GFP) zebrafish. The targeting efficiency was detected by polymerase chain reaction amplification and Sanger sequencing. Zebrafish hair cells were observed by laser scanning confocal microscopy in vivo. The morphology of the otoliths and semicircular canals were analyzed. All animal experiments were approved by the Animal Care and Use Committee of Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University (approval No. 2016-KY-040) on March 3, 2016. Results: The pou4f3-mutant Tg(Brn3c:GFP) zebrafish line was successfully established. Fluorescence observation suggested that hair cell development was delayed in pou4f3-knockout zebrafish. Knockout of pou4f3 also induced defects in the otoliths and semicircular canals and impaired ear function in zebrafish. Conclusion: A CRISPR/Cas9-mediated pou4f3 mutant Tg(Brn3c:GFP) zebrafish model was established for the first time to demonstrate the essential role of pou4f3 in zebrafish ear development. Our study provides a highly efficient method for the establishment of a visualized model of gene knockout zebrafish and has the potential to allow high-throughput drug screening to explore therapeutics for related diseases.