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Cell Reports Apr 2024Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea....
Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.
Topics: Animals; Receptors, AMPA; Mice; Spiral Ganglion; Hearing; Cochlea; Post-Synaptic Density; Mice, Knockout; Hair Cells, Auditory, Inner; Mice, Inbred C57BL; Synapses; Receptors, G-Protein-Coupled
PubMed: 38564333
DOI: 10.1016/j.celrep.2024.114025 -
BioRxiv : the Preprint Server For... Mar 2024Models of speech perception are centered around a hierarchy in which auditory representations in the thalamus propagate to primary auditory cortex, then to the lateral...
Models of speech perception are centered around a hierarchy in which auditory representations in the thalamus propagate to primary auditory cortex, then to the lateral temporal cortex, and finally through dorsal and ventral pathways to sites in the frontal lobe. However, evidence for short latency speech responses and low-level spectrotemporal representations in frontal cortex raises the question of whether speech-evoked activity in frontal cortex strictly reflects downstream processing from lateral temporal cortex or whether there are direct parallel pathways from the thalamus or primary auditory cortex to the frontal lobe that supplement the traditional hierarchical architecture. Here, we used high-density direct cortical recordings, high-resolution diffusion tractography, and hemodynamic functional connectivity to evaluate for evidence of direct parallel inputs to frontal cortex from low-level areas. We found that neural populations in the frontal lobe show speech-evoked responses that are synchronous or occur earlier than responses in the lateral temporal cortex. These short latency frontal lobe neural populations encode spectrotemporal speech content indistinguishable from spectrotemporal encoding patterns observed in the lateral temporal lobe, suggesting parallel auditory speech representations reaching temporal and frontal cortex simultaneously. This is further supported by white matter tractography and functional connectivity patterns that connect the auditory nucleus of the thalamus (medial geniculate body) and the primary auditory cortex to the frontal lobe. Together, these results support the existence of a robust pathway of parallel inputs from low-level auditory areas to frontal lobe targets and illustrate long-range parallel architecture that works alongside the classical hierarchical speech network model.
PubMed: 38562883
DOI: 10.1101/2024.03.19.585648 -
Experimental Biology and Medicine... 2024Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been...
Tinnitus is a disturbing condition defined as the occurrence of acoustic hallucinations with no actual sound. Although the mechanisms underlying tinnitus have been explored extensively, the pathophysiology of the disease is not completely understood. Moreover, genes and potential treatment targets related to auditory hallucinations remain unknown. In this study, we examined transcriptional-profile changes in the medial geniculate body after noise-induced tinnitus in rats by performing RNA sequencing and validated differentially expressed genes via quantitative polymerase chain reaction analysis. The rat model of tinnitus was established by analyzing startle behavior based on gap-pre-pulse inhibition of acoustic startles. We identified 87 differently expressed genes, of which 40 were upregulated and 47 were downregulated. Pathway-enrichment analysis revealed that the differentially enriched genes in the tinnitus group were associated with pathway terms, such as coronavirus disease COVID-19, neuroactive ligand-receptor interaction. Protein-protein-interaction networks were established, and two hub genes (Rpl7a and AC136661.1) were identified among the selected genes. Further studies focusing on targeting and modulating these genes are required for developing potential treatments for noise-induced tinnitus in patients.
Topics: Humans; Rats; Animals; Tinnitus; Geniculate Bodies; Noise
PubMed: 38562529
DOI: 10.3389/ebm.2024.10057 -
Frontiers in Medicine 2024Systemic sclerosis (SSc) is a disease of a very heterogeneous clinical picture and immunological profile with progression rate that varies between individuals. Although...
BACKGROUND
Systemic sclerosis (SSc) is a disease of a very heterogeneous clinical picture and immunological profile with progression rate that varies between individuals. Although hearing deterioration is not a complaint that comes to the fore in SSc patients, as it is not life-threatening compared to many other more severe symptoms of this disease, it can significantly impair the quality of life. Medical literature concerning this problem is rather scarce.
MATERIALS AND METHODS
In this article we systematically reviewed the medical publications concerning hearing impairment in patients with systemic sclerosis to evaluate current understanding of this complex problem. Following PRISMA guidelines a total of 19 papers were found and analysed including 11 original studies and 8 case reports.
RESULTS
Although it seems that hearing impairment in SSc patients is relatively more common than in the general population, based on the analysis of available literature, no firm conclusions regarding its frequency and pathomechanism can be drawn yet. Microangiopathy leading to damage to the sensory cells of the inner ear is suspected to be the main mechanism of hearing loss, although damage to the higher levels of the auditory pathway appears to be underestimated due to incomplete audiological diagnosis.
CONCLUSION
Undoubtedly, the reason for the difficulty in such an evaluation are the complex and still not fully elucidated pathomechanism of SSc, the individually variable dynamics of the disease and the unique heterogeneity of symptoms. Nevertheless, further studies in larger and appropriately selected groups of patients, focused more on the dynamics of microangiopathy and not solely on clinical symptoms could provide answers to many key questions in this regard.
PubMed: 38562372
DOI: 10.3389/fmed.2024.1322170 -
Frontiers in Neuroscience 2024Patients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains...
Sound-localization-related activation and functional connectivity of dorsal auditory pathway in relation to demographic, cognitive, and behavioral characteristics in age-related hearing loss.
BACKGROUND
Patients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear.
MATERIALS AND METHODS
Using a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory "where" pathway based on the data of previous literatures and young normal hearing listeners ( = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients ( = 22).
RESULTS
We found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function.
CONCLUSION
Consistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right-left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization.
PubMed: 38562303
DOI: 10.3389/fnins.2024.1353413 -
Journal of Vision Apr 2024The sudden onset of a visual object or event elicits an inhibition of eye movements at latencies approaching the minimum delay of visuomotor conductance in the brain....
The sudden onset of a visual object or event elicits an inhibition of eye movements at latencies approaching the minimum delay of visuomotor conductance in the brain. Typically, information presented via multiple sensory modalities, such as sound and vision, evokes stronger and more robust responses than unisensory information. Whether and how multisensory information affects ultra-short latency oculomotor inhibition is unknown. In two experiments, we investigate smooth pursuit and saccadic inhibition in response to multisensory distractors. Observers tracked a horizontally moving dot and were interrupted by an unpredictable visual, auditory, or audiovisual distractor. Distractors elicited a transient inhibition of pursuit eye velocity and catch-up saccade rate within ∼100 ms of their onset. Audiovisual distractors evoked stronger oculomotor inhibition than visual- or auditory-only distractors, indicating multisensory response enhancement. Multisensory response enhancement magnitudes were equal to the linear sum of responses to component stimuli. These results demonstrate that multisensory information affects eye movements even at ultra-short latencies, establishing a lower time boundary for multisensory-guided behavior. We conclude that oculomotor circuits must have privileged access to sensory information from multiple modalities, presumably via a fast, subcortical pathway.
Topics: Humans; Reaction Time; Pursuit, Smooth; Brain; Saccades; Memory; Photic Stimulation
PubMed: 38558158
DOI: 10.1167/jov.24.4.3 -
Journal of Clinical Medicine Mar 2024Neuroplasticity is a complex process that is heightened during time-sensitive periods of pre- and postnatal brain development. It continues, albeit to a lesser extent,... (Review)
Review
Neuroplasticity is a complex process that is heightened during time-sensitive periods of pre- and postnatal brain development. It continues, albeit to a lesser extent, throughout adolescence and young adulthood. Congenital visual deprivation is well-known and explored in human-model behavioral research. In this study, we review existing research on neuroadaptations and neuroplasticity of the visual pathway as a result of inherited retinal diseases (IRD), focusing on data concerning congenital bilateral visual deprivation in humans published in PubMed in the past 5 years, including 18 articles. We highlight evidence about the anatomical and behavioral aspects of neuroplasticity as different brain responses to different types of visual deprivation. We also focus on various very interesting aspects of the cross-modal functional reorganization of the visual and auditory cortex as an example of brain plasticity due to combined visual and auditory loss. Our study shows that central nervous system magnetic resonance imaging (MRI) advancements have allowed researchers to report previously elusive anatomical evidence. Patients with a known mechanism of IRD-examined with high magnetic field MRI and functional MRI-have been proven to be adequate models to explore neuroadaptations of the visual pathway due to bilateral, early, and late visual deprivation.
PubMed: 38541998
DOI: 10.3390/jcm13061775 -
Journal of Cellular and Molecular... Apr 2024Hearing loss is a clinically and genetically heterogeneous disorder, with over 148 genes and 170 loci associated with its pathogenesis. The spectrum and frequency of... (Review)
Review
Hearing loss is a clinically and genetically heterogeneous disorder, with over 148 genes and 170 loci associated with its pathogenesis. The spectrum and frequency of causal variants vary across different genetic ancestries and are more prevalent in populations that practice consanguineous marriages. Pakistan has a rich history of autosomal recessive gene discovery related to non-syndromic hearing loss. Since the first linkage analysis with a Pakistani family that led to the mapping of the DFNB1 locus on chromosome 13, 51 genes associated with this disorder have been identified in this population. Among these, 13 of the most prevalent genes, namely CDH23, CIB2, CLDN14, GJB2, HGF, MARVELD2, MYO7A, MYO15A, MSRB3, OTOF, SLC26A4, TMC1 and TMPRSS3, account for more than half of all cases of profound hearing loss, while the prevalence of other genes is less than 2% individually. In this review, we discuss the most common autosomal recessive non-syndromic hearing loss genes in Pakistani individuals as well as the genetic mapping and sequencing approaches used to discover them. Furthermore, we identified enriched gene ontology terms and common pathways involved in these 51 autosomal recessive non-syndromic hearing loss genes to gain a better understanding of the underlying mechanisms. Establishing a molecular understanding of the disorder may aid in reducing its future prevalence by enabling timely diagnostics and genetic counselling, leading to more effective clinical management and treatments of hearing loss.
Topics: Humans; Genes, Recessive; Pakistan; Mutation; Hearing Loss; Pedigree; Membrane Proteins; Neoplasm Proteins; Serine Endopeptidases; MARVEL Domain Containing 2 Protein; Deafness
PubMed: 38534090
DOI: 10.1111/jcmm.18119 -
Scientific Reports Mar 2024Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field...
Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.
Topics: Mice; Animals; Geniculate Bodies; Auditory Cortex; Neurons; Neurites; Auditory Pathways; Thalamus
PubMed: 38528192
DOI: 10.1038/s41598-024-57815-3 -
Audiology Research Feb 2024Usher syndrome (US) is a clinically and genetically heterogeneous disorder that involves three main features: sensorineural hearing loss, retinitis pigmentosa (RP), and... (Review)
Review
Usher syndrome (US) is a clinically and genetically heterogeneous disorder that involves three main features: sensorineural hearing loss, retinitis pigmentosa (RP), and vestibular impairment. With a prevalence of 4-17/100,000, it is the most common cause of deaf-blindness worldwide. Genetic research has provided crucial insights into the complexity of US. Among nine confirmed causative genes, and are major players in US types 1 and 2, respectively, whereas is the sole confirmed gene associated with type 3. Variants in these genes also contribute to isolated forms of hearing loss and RP, indicating intersecting molecular pathways. While hearing loss can be adequately managed with hearing aids or cochlear implants (CIs), approved RP treatment modalities are lacking. Gene replacement and editing, antisense oligonucleotides, and small-molecule drugs hold promise for halting RP progression and restoring vision, enhancing patients' quality of life. Massively parallel sequencing has identified gene variants (e.g., in ) that influence CI results. Accordingly, preoperative genetic examination appears valuable for predicting CI success. To explore genetic mutations in CI recipients and establish correlations between implant outcomes and involved genes, we comprehensively reviewed the literature to gather data covering a broad spectrum of CI outcomes across all known US-causative genes. Implant outcomes were categorized as excellent or very good, good, poor or fair, and very poor. Our review of 95 cochlear-implant patients with US, along with their CI outcomes, revealed the importance of presurgical genetic testing to elucidate potential challenges and provide tailored counseling to improve auditory outcomes. The multifaceted nature of US demands a comprehensive understanding and innovative interventions. Genetic insights drive therapeutic advancements, offering potential remedies for the retinal component of US. The synergy between genetics and therapeutics holds promise for individuals with US and may enhance their sensory experiences through customized interventions.
PubMed: 38525684
DOI: 10.3390/audiolres14020023