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Expression pattern of cochlear microRNAs in the mammalian auditory hindbrain.

ABSTRACT: The auditory system comprises the auditory periphery, engaged in sound transduction and the central auditory system, implicated in auditory information processing and perception. Recently, evidence mounted that the mammalian peripheral and central auditory systems share a number of genes critical for proper development and function. This bears implication for auditory rehabilitation and evolution of the auditory system. To analyze to which extent microRNAs (miRNAs) belong to genes shared between both systems, we characterize the expression pattern of 12 cochlea-abundant miRNAs in the central auditory system. Quantitative real-time PCR (qRT-PCR) demonstrated expression of all 12 genes in the cochlea, the auditory hindbrain and the non-auditory prefrontal cortex (PFC) at embryonic stage (E)16 and postnatal stages (P)0 and P30. Eleven of them showed differences in expression between tissues and nine between the developmental time points. Hierarchical cluster analysis revealed that the temporal expression pattern in the auditory hindbrain was more similar to the PFC than to the cochlea. Spatiotemporal expression analysis by RNA in situ hybridization demonstrated widespread expression throughout the cochlear nucleus complex (CNC) and the superior olivary complex (SOC) during postnatal development. Altogether, our data indicate that miRNAs represent a relevant class of genetic factors functioning across the auditory system. Given the importance of gene regulatory network (GRN) components for development, physiology and evolution, the 12 miRNAs provide promising entry points to gain insights into their molecular underpinnings in the auditory system.

SUBMITTER: Krohs C

PROVIDER: S-EPMC7904729 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Expression pattern of cochlear microRNAs in the mammalian auditory hindbrain.

Krohs Constanze C Bordeynik-Cohen Mor M Messika-Gold Naama N Elkon Ran R Avraham Karen B KB Nothwang Hans Gerd HG

Cell and tissue research 20201106 2

The auditory system comprises the auditory periphery, engaged in sound transduction and the central auditory system, implicated in auditory information processing and perception. Recently, evidence mounted that the mammalian peripheral and central auditory systems share a number of genes critical for proper development and function. This bears implication for auditory rehabilitation and evolution of the auditory system. To analyze to which extent microRNAs (miRNAs) belong to genes shared between ...[more]

PMID: 33156384

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Project description:Spatial hearing skills are essential for children as they grow, learn and play. These skills provide critical cues for determining the locations of sources in the environment, and enable segregation of important sounds, such as speech, from background maskers or interferers. Spatial hearing depends on availability of monaural cues and binaural cues. The latter result from integration of inputs arriving at the two ears from sounds that vary in location. The binaural system has exquisite mechanisms for capturing differences between the ears in both time of arrival and intensity. The major cues that are thus referred to as being vital for binaural hearing are: interaural differences in time (ITDs) and interaural differences in levels (ILDs). In children with normal hearing (NH), spatial hearing abilities are fairly well developed by age 4-5 years. In contrast, most children who are deaf and hear through cochlear implants (CIs) do not have an opportunity to experience normal, binaural acoustic hearing early in life. These children may function by having to utilize auditory cues that are degraded with regard to numerous stimulus features. In recent years there has been a notable increase in the number of children receiving bilateral CIs, and evidence suggests that while having two CIs helps them function better than when listening through a single CI, these children generally perform worse than their NH peers. This paper reviews some of the recent work on bilaterally implanted children. The focus is on measures of spatial hearing, including sound localization, release from masking for speech understanding in noise and binaural sensitivity using research processors. Data from behavioral and electrophysiological studies are included, with a focus on the recent work of the authors and their collaborators. The effects of auditory plasticity and deprivation on the emergence of binaural and spatial hearing are discussed along with evidence for reorganized processing from both behavioral and electrophysiological studies. The consequences of both unilateral and bilateral auditory deprivation during development suggest that the relevant set of issues is highly complex with regard to successes and the limitations experienced by children receiving bilateral cochlear implants. This article is part of a Special Issue entitled <Annual Reviews 2016>.

Project description:ObjectivesIn this study, we aimed to (1) review the long-term outcomes of cochlear implantation in children with cochlear nerve aplasia and (2) compare the development of their auditory and speech abilities to children with normal-sized cochlear nerves.DesignThis is a retrospective case-control study. Patients who underwent unilateral cochlear implant (CI) surgery in a tertiary referral center from September 2012 to December 2018 were reviewed. The study group included 55 children with cochlear nerve aplasia diagnosed using preoperative images. The control group included 35 children with normal-sized cochlear nerves. The control group did not differ from the study group in terms of age at implantation, pre-implantation auditory and speech abilities, or the electrode array type. Cochlear implantation outcomes were assessed using a test battery, including the Categories of Auditory Performance (CAP) score, the Speech Intelligibility Rating (SIR) score, behavioral audiometry, and closed- or open-set speech recognition tests. The development of auditory and speech abilities was compared between the two groups using Generalized Linear Mixed-effect Models.ResultsThe mean duration of CI usage was 4.5 years (SD = 1.5, range = 2.0 to 9.5) in the study group. The CAP scores, SIR scores, and aided hearing thresholds improved significantly post-implantation in the study group, but were significantly poorer than those in the control group. Generalized Linear Mixed-effect Models showed that the development of CAP and SIR scores was significantly slower in the study group than in the control group. Overall, 27 (49%) children with cochlear nerve aplasia had some degree of open-set speech perception skills, but the monosyllabic and bisyllabic word recognition rates were significantly lower than those in the control group.ConclusionFor children with cochlear nerve aplasia, auditory perception and speech intelligibility continued to improve in the long-term follow-up, but this progress was significantly slower than in children with normal-sized cochlear nerves. Most children with cochlear nerve aplasia could obtain the ability of common phrase perception and understanding simple spoken language with consistent CI usage and auditory rehabilitation.

Project description:BackgroundThe auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system.Methodology/principal findingsCochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses.Conclusions/significanceThese results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea.

Dataset Information

Expression pattern of cochlear microRNAs in the mammalian auditory hindbrain.

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Expression pattern of cochlear microRNAs in the mammalian auditory hindbrain.

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