https://www.cell.com/neuron/pdf/S0896-6273(08)00584-9.pdf

Making an Effort to Listen: Mechanical Amplification in the Ear

Mechanotransduction by Hair Cells: Models, Molecules, and Mechanisms

The SLC26 gene family of anion transporters and channels.

The sensitivity, frequency resolution and dynamic range of hearing depend upon the cochlear active process, a mechanical-amplification system within the cochlea In this Review, Hudspeth summarizes evidence that these features result from the operation of hair cells near a dynamical instability, the Hopf bifurcation Uniquely among human senses, hearing is not simply a passive response to stimulation Our auditory system is instead enhanced by an active process in cochlear hair cells that amplifies acoustic signals several hundred-fold, sharpens frequency selectivity and broadens the ear's dynamic range Active motility of the mechanoreceptive hair bundles underlies the active process in amphibians and some reptiles; in mammals, this mechanism operates in conjunction with prestin-based somatic motility Both individual hair bundles and the cochlea as a whole operate near a dynamical instability, the Hopf bifurcation, which accounts for the cardinal features of the active process

Integrating the active process of hair cells with cochlear function

Progressive hearing loss is common in the human population, but little is known about the molecular basis. We report a new N-ethyl-N-nitrosurea (ENU)-induced mouse mutant, diminuendo, with a single base change in the seed region of Mirn96. Heterozygotes show progressive loss of hearing and hair cell anomalies, whereas homozygotes have no cochlear responses. Most microRNAs are believed to downregulate target genes by binding to specific sites on their mRNAs, so mutation of the seed should lead to target gene upregulation. Microarray analysis revealed 96 transcripts with significantly altered expression in homozygotes; notably, Slc26a5, Ocm, Gfi1, Ptprq and Pitpnm1 were downregulated. Hypergeometric P-value analysis showed that hundreds of genes were upregulated in mutants. Different genes, with target sites complementary to the mutant seed, were downregulated. This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally.

/pdf/an-enu-induced-mutation-of-mir-96-associated-with-2mgc4znowb.pdf

Wendy H.Y. Cheng

Papers

Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification