Differential outcomes of high-fat diet on age-related rescaling of cochlear frequency place coding.

Auditory frequency coding is place-specific, which depends on the mechanical coupling of the basilar membrane-outer hair cell (OHC)-tectorial membrane network. Prestin-based OHC electromotility improves cochlear frequency selectivity and sensitivity. Cochlear amplification determines the frequency coding wherein discrete sound frequencies find a 'best' place along the cochlear length. Loss of OHC is the leading cause of age-related hearing loss (ARHL) and is the most common cause of sensorineural hearing loss and compromised speech perception. Lipid interaction with Prestin impacts OHC function. It has been established that high-fat diet (HFD) is associated with ARHL. To determine whether genetic background and metabolism preserve cochlear frequency place coding, we examined the effect of HFD in C57BL/6J (B6) and CBA/CaJ (CBA) on ARHL.We found a significant rescuing effect on ARHL in aged B6 HFD cohort. Prestin levels and cell sizes were better maintained in the experimental B6-HFD group. We also found that distortion product otoacoustic emission (DPOAE) group delay measurement was preserved, which suggested stable frequency place coding. In contrast, the response to HFD in the CBA cohort was modest with no appreciable benefit to hearing threshold. Notably, group delay was shortened with age along with the control. In addition, the frequency dependent OHC nonlinear capacitance gradient was most pronounced at young age but decreased with age. Cochlear RNA-seq analysis revealed differential TRPV1 expression and lipid homeostasis. Activation of TRPV1 and downregulation of arachidonic acid led to downregulation of inflammatory response in B6 HFD, which protects the cochlea from ARHL. The genetic background and metabolic state-derived changes in OHC morphology and function collectively contribute to a redefined cochlear frequency place coding and improved age-related pitch perception.

Prestin derived OHC surface area reduction underlies age-related rescaling of frequency place coding.

Outer hair cells (OHC) are key to the mammalian cochlear amplifier, powered by the lateral membrane protein Prestin. In this study, we explored age-related OHC changes and how the changes affected hearing in mouse. OHC nonlinear membrane capacitance measurements revealed that, starting upon completion of postnatal auditory development, a continuous reduction of total Prestin in OHCs accompanied by a significant reduction in their cell surface area. Prestin's density is unaffected by Prestin level drop over the whole age range tested, suggesting that the OHC size reduction is Prestin-dependent. Stereocilia length in aged OHCs remained unchanged but the first row stereocilia on the aged inner hair cells (IHCs) were elongated. Distortion product otoacoustic emission (DPOAE) group delays became longer with aging, suggesting an apical shift in vibration on basilar membrane. Acoustic lesion experiments revealed an apical shift in damage place in old cochleae accompanied by a shallower progression in synaptic damage over a wider frequency range that was indicative of a broader frequency filter. Overall, these findings suggest that in aging cochlea, a shift in frequency place coding could occur due to the changes in cochlear active and passive mechanics. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.