ABSTRACT
In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca2+ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.
Subject(s)
Animals , Humans , Mice , Cochlea/metabolism , Hair Cells, Auditory, Outer/metabolism , Hearing , Mammals/metabolism , Mice, Knockout , Molecular Motor Proteins/metabolismABSTRACT
Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
Subject(s)
Animals , Mice , Artificial Intelligence , Cochlea/metabolism , Hair Cells, Auditory, Inner , Mitochondria , Synapses/metabolismABSTRACT
Os autores estudam a eletroestimulaçäo no tratamento do zumbido idiopático severo. Foram estudados 10 pacientes do Hospital das Clínicas da Faculdade de Medicina da Universidade de Säo Paulo, utilizando-se um estimulador que basicamente se compunha de um gerador de sinais de rádio de baixa freqüência (60kHz) que produz um sinal que facilmente penetra através da pele. A estimulaçäo é feita através de um eletrodo de superfície colocado na regiäo mastóidea bilateralmente. Houve melhora clínica em três dos dez pacientes, sem, entretanto, suspressäo do zumbido em nenhum deles. Estes reultados encorajam estudos co-relacionando etiologia, alteraçöes audiométricas e eletroestimulaçäo, que poderiam ser úteis em algumas etiologias do zumbido