Dataset Information

GRM7 variants associated with age-related hearing loss based on auditory perception.

ABSTRACT: Age-related hearing impairment (ARHI), or presbycusis, is a common condition of the elderly that results in significant communication difficulties in daily life. Clinically, it has been defined as a progressive loss of sensitivity to sound, starting at the high frequencies, inability to understand speech, lengthening of the minimum discernable temporal gap in sounds, and a decrease in the ability to filter out background noise. The causes of presbycusis are likely a combination of environmental and genetic factors. Previous research into the genetics of presbycusis has focused solely on hearing as measured by pure-tone thresholds. A few loci have been identified, based on a best ear pure-tone average phenotype, as having a likely role in susceptibility to this type of hearing loss; and GRM7 is the only gene that has achieved genome-wide significance. We examined the association of GRM7 variants identified from the previous study, which used an European cohort with Z-scores based on pure-tone thresholds, in a European-American population from Rochester, NY (N = 687), and used novel phenotypes of presbycusis. In the present study mixed modeling analyses were used to explore the relationship of GRM7 haplotype and SNP genotypes with various measures of auditory perception. Here we show that GRM7 alleles are associated primarily with peripheral measures of hearing loss, and particularly with speech detection in older adults.

SUBMITTER: Newman DL

PROVIDER: S-EPMC3705704 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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GRM7 variants associated with age-related hearing loss based on auditory perception.

Newman Dina L DL Fisher Laurel M LM Ohmen Jeffrey J Parody Robert R Fong Chin-To CT Frisina Susan T ST Mapes Frances F Eddins David A DA Robert Frisina D D Frisina Robert D RD Friedman Rick A RA

Hearing research 20121025 1-2

Age-related hearing impairment (ARHI), or presbycusis, is a common condition of the elderly that results in significant communication difficulties in daily life. Clinically, it has been defined as a progressive loss of sensitivity to sound, starting at the high frequencies, inability to understand speech, lengthening of the minimum discernable temporal gap in sounds, and a decrease in the ability to filter out background noise. The causes of presbycusis are likely a combination of environmental ...[more]

PMID: 23102807

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Project description:Key pointsSound information is transmitted by different subtypes of spiral ganglion neurons (SGN) from the ear to the brain. Selective damage of SGN peripheral synapses (cochlear synaptopathy) is widely recognized as one of the primary mechanisms of hearing loss, whereas the mechanisms at the SGN central synapses remain unclear. We report that different subtypes of SGN central synapses converge at different ratios onto individual target cochlear nucleus neurons with distinct physiological properties, and show biased morphological and physiological changes during age-related hearing loss (ARHL). The results reveal a new dimension in cochlear nucleus neural circuitry that systematically reassembles and processes auditory information from different SGN subtypes, which is altered during ageing and probably contributes to the development of ARHL. In addition to known cochlear synaptopathy, the present study shows that SGN central synapses are also pathologically changed during ageing, which collectively helps us better understand the structure and function of SGNs during ARHL.AbstractSound information is transmitted from the cochlea to the brain by different subtypes of spiral ganglion neurons (SGN), which show varying degrees of vulnerability under pathological conditions. Selective cochlear synaptopathy, the preferential damage of certain subtypes of SGN peripheral synapses, has been recognized as one of the main mechanisms of hearing loss. The organization and function of the auditory nerve (AN) central synapses from different subtypes of SGNs remain unclear, including how different AN synapses reassemble onto individual neurons in the cochlear nucleus, as well as how they differentially change during hearing loss. Combining immunohistochemistry with electrophysiology, we investigated the convergence pattern and subtype-specific synaptopathy of AN synapses at the endbulb of Held, as well as the response properties of their postsynaptic bushy neurons in CBA/CaJ mice of either sex under normal hearing and age-related hearing loss (ARHL). We found that calretinin-expressing (type Ia ) and non-calretinin-expressing (type Ib /Ic ) endbulbs converged along a continuum of different ratios onto individual bushy neurons with varying physiological properties. Endbulbs degenerated during ageing in parallel with ARHL. Furthermore, the degeneration was more severe in non-calretinin-expressing synapses, which correlated with a gradual decrease in bushy neuron subpopulation predominantly innervated by these inputs. These synaptic and cellular changes were profound in middle-aged mice when their hearing thresholds were still relatively normal and prior to severe ARHL. Our findings suggest that biased AN central synaptopathy and the correlated shift in cochlear nucleus neuronal composition play significant roles in weakened auditory input and altered central auditory processing during ARHL.

Project description:Introduction : Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL). Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL. Methods : Fifty-six listeners (60-72 y/o), 35 participants with ARHL, and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed-training, and no-training group). Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1) Speech-in-noise, (2) time compressed speech, and (3) competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results : Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions : ARHL did not preclude auditory perceptual learning but there was little generalization to untrained conditions. We suggest that most training-related changes occurred at higher level task-specific cognitive processes in both groups. However, these were enhanced by high quality perceptual representations in the normal-hearing group. In contrast, some training-related changes have also occurred at the level of phonemic representations in the ARHL group, consistent with an interaction between bottom-up and top-down processes.

Project description:Inbred strain variants of the Cdh23 gene have been shown to influence the onset and progression of age-related hearing loss (AHL) in mice. In linkage backcrosses, the recessive Cdh23 allele (ahl) of the C57BL/6J strain, when homozygous, confers increased susceptibility to AHL, while the dominant allele (Ahl+) of the CBA/CaJ strain confers resistance. To determine the isolated effects of these alleles on different strain backgrounds, we produced the reciprocal congenic strains B6.CBACa-Cdh23(Ahl)(+) and CBACa.B6-Cdh23(ahl) and tested 15-30 mice from each for hearing loss progression. ABR thresholds for 8 kHz, 16 kHz, and 32 kHz pure-tone stimuli were measured at 3, 6, 9, 12, 15 and 18 months of age and compared with age-matched mice of the C57BL/6J and CBA/CaJ parental strains. Mice of the C57BL/6N strain, which is the source of embryonic stem cells for the large International Knockout Mouse Consortium, were also tested for comparisons with C57BL/6J mice. Mice of the C57BL/6J and C57BL/6N strains exhibited identical hearing loss profiles: their 32 kHz ABR thresholds were significantly higher than those of CBA/CaJ and congenic strain mice by 6 months of age, and their 16 kHz thresholds were significantly higher by 12 months. Thresholds of the CBA/CaJ, the B6.CBACa-Cdh23(Ahl)(+), and the CBACa.B6-Cdh23(ahl) strain mice differed little from one another and only slightly increased throughout the 18-month test period. Hearing loss, which corresponded well with cochlear hair cell loss, was most profound in the C57BL/6J and C57BL/6NJ strains. These results indicate that the CBA/CaJ-derived Cdh23(Ahl)(+) allele dramatically lessens hearing loss and hair cell death in an otherwise C57BL/6J genetic background, but that the C57BL/6J-derived Cdh23(ahl) allele has little effect on hearing loss in an otherwise CBA/CaJ background. We conclude that although Cdh23(ahl) homozygosity is necessary, it is not by itself sufficient to account for the accelerated hearing loss of C57BL/6J mice.

Project description:ObjectivesThe goal of this study was to identify the effects of auditory deprivation (age-related hearing loss) and auditory stimulation (history of hearing aid use) on the neural registration of sound across two stimulus presentation conditions: (1) equal sound pressure level and (2) equal sensation level.DesignWe used a between-groups design, involving three groups of 14 older adults (n = 42; 62 to 84 years): (1) clinically defined normal hearing (≤25 dB from 250 to 8000 Hz, bilaterally), (2) bilateral mild-moderate/moderately severe sensorineural hearing loss who have never used hearing aids, and (3) bilateral mild-moderate/moderately severe sensorineural hearing loss who have worn bilateral hearing aids for at least the past 2 years.ResultsThere were significant delays in the auditory P1-N1-P2 complex in older adults with hearing loss compared with their normal hearing peers when using equal sound pressure levels for all participants. However, when the degree and configuration of hearing loss were accounted for through the presentation of equal sensation level stimuli, no latency delays were observed. These results suggest that stimulus audibility modulates P1-N1-P2 morphology and should be controlled for when defining deprivation and stimulus-related neuroplasticity in people with hearing loss. Moreover, a history of auditory stimulation, in the form of hearing aid use, does not appreciably alter the neural registration of unaided auditory evoked brain activity when quantified by the P1-N1-P2.ConclusionsWhen comparing auditory cortical responses in older adults with and without hearing loss, stimulus audibility, and not hearing loss-related neurophysiological changes, results in delayed response latency for those with age-related hearing loss. Future studies should carefully consider stimulus presentation levels when drawing conclusions about deprivation- and stimulation-related neuroplasticity. Additionally, auditory stimulation, in the form of a history of hearing aid use, does not significantly affect the neural registration of sound when quantified using the P1-N1-P2-evoked response.

Dataset Information

GRM7 variants associated with age-related hearing loss based on auditory perception.

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GRM7 variants associated with age-related hearing loss based on auditory perception.

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