Regeneration and replacement in the vertebrate inner ear.

Deafness affects more than 40 million people in the UK and the USA, and many more world-wide. The primary cause of hearing loss is damage to or death of the sensory receptor cells in the inner ear, the hair cells. Birds can readily regenerate their cochlear hair cells but the mammalian cochlea has shown no ability to regenerate after damage. Current research efforts are focusing on gene manipulation, gene therapy and stem cell transplantation for repairing or replacing damaged mammalian cochlear hair cells, which could lead to therapies for treating deafness in humans.

Return of function after hair cell regeneration.

The ultimate goal of hair cell regeneration is to restore functional hearing. Because birds begin perceiving and producing song early in life, they provide a propitious model for studying not only whether regeneration of lost hair cells can return auditory sensitivity but also whether this regenerated periphery can restore complex auditory perception and production. They are the only animal where hair cell regeneration occurs naturally after hair cell loss and where the ability to correctly perceive and produce complex acoustic signals is critical to procreation and survival. The purpose of this review article is to survey the most recent literature on behavioral measures of auditory functional return in adult birds after hair cell regeneration. The first portion of the review summarizes the effect of ototoxic drug induced hair cell loss and regeneration on hearing loss and recovery for pure tones. The second portion reviews studies of complex, species-specific vocalization discrimination and recognition after hair cell regeneration. Finally, we discuss the relevance of temporary hearing loss and recovery through hair cell regeneration on complex call and song production. Hearing sensitivity is restored, except for the highest frequencies, after hair cell regeneration in birds, but there are enduring changes to complex auditory perception. These changes do not appear to provide any obstacle to future auditory or vocal learning. This article is part of a Special Issue entitled "Inner Ear Development and Regeneration".

Perception of complex sounds in budgerigars (Melopsittacus undulatus) with temporary hearing loss.

Songbirds and parrots deafened as nestlings fail to develop normal vocalizations, while birds deafened as adults show a gradual deterioration in the quality and precision of vocal production. Beyond this, little is known about the effect of hearing loss on the perception of vocalizations. Here, we induced temporary hearing loss in budgerigars with kanamycin and tested several aspects of the hearing, including the perception of complex, species-specific vocalizations. The ability of these birds to discriminate among acoustically distinct vocalizations was not impaired but the ability to make fine-grain discriminations among acoustically similar vocalizations was affected, even weeks after the basilar papilla had been repopulated with new hair cells. Interestingly, these birds were initially unable to recognize previously familiar contact calls in a classification task-suggesting that previously familiar vocalizations sounded unfamiliar with new hair cells. Eventually, in spite of slightly elevated absolute thresholds, the performance of birds on discrimination and perceptual recognition of vocalizations tasks returned to original levels. Thus, even though vocalizations may initially sound different with new hair cells, there are only minimal long-term effects of temporary hearing loss on auditory perception, recognition of species-specific vocalizations, or other aspects of acoustic communication in these birds.

Hair cell regeneration: an exciting phenomenon...but will restoring hearing and balance be possible?

Sensory hair cells of the inner ear are susceptible to damage from a variety of sources including aging, genetic defects, and environmental stresses such as loud noises or chemotherapeutic drugs. Unfortunately, the consequence of this damage in humans is often permanent hearing/balance problems. The discovery that hair cells can regenerate in birds and other nonmammalian vertebrates has fueled a wide range of studies that are designed to find ways of restoring hearing and balance after such damage. In this review, we will discuss some of the key recent findings in sensory hair cell regeneration and what they mean for audiologists and other hearing healthcare practitioners.

Sensorineural hearing loss in children and adults with Williams syndrome.

Williams syndrome (WS) is a genetic neurodevelopmental disorder, most often accompanied by mild-to-moderate mental retardation. Individuals with WS show unique communication strengths and impairments that are challenging to treat in community, educational, and vocational settings. Many issues regarding characteristics of auditory sensitivity in WS remain to be resolved. Our purpose was to obtain behavioral (screening and pure-tone audiometry) and objective (distortion product otoacoustic emission-DPOAE) measures of auditory system function from a group of 27 individuals with WS, 6-48 years of age. These measures were gathered both at an international professional conference (n = 19) and in a clinic setting (n = 8). In the behavioral screening conditions, 16/19 (84%) of the individuals failed the hearing screening; and in the behavioral diagnostic hearing condition, 6/8 (75%) demonstrated sensorineural hearing loss (SNHL) and 1/8 demonstrated a hearing loss of undetermined type. In the objective DPOAE testing, 19/25 (76%) had DPOAE absolute amplitudes below the 5th percentile for ears with normal hearing [Gorga et al. (1997); Ear Hear 18(6):440-455]. We report SNHL in 14/18 (78%) of school-age children with WS. Post hoc analyses revealed a significant effect for age, suggesting a pattern of progressive hearing loss. An effect size analysis indicated a clinically meaningful difference in the hearing sensitivity between school-aged children and adults in the high frequencies (4,000 and 8,000 Hz). Similar hearing loss phenotype was observed in patients with familial nonsyndromic supravalvular aortic stenosis (SVAS), suggesting that molecular defects in the elastin gene in the pathogenesis of SNHL in WS. This study highlights the importance of early and regular hearing testing for WS patients and suggests that elastin may have a previously unappreciated function in maintaining hearing sensitivity.