Structural recovery from sound and aminoglycoside damage in the avian cochlea

Hair cell regeneration in the mature avian cochlea occurs in response to trauma that causes the death of some or all of the existing hair cell population. In general, this trauma has been introduced experimentally by either sound overexposure or treatment of the bird with high doses of aminoglycoside antibiotics. When injured hair cells are ejected from the sensory epithelium, the nonsensory supporting cells respond by re-entering the cell cycle and proliferating or by transdifferentiating directly into hair cells without a mitotic event. The new hair cells mature in a manner similar to that seen during embryonic development. They make connections with the overlying tectorial membrane and the afferent and efferent cochlear nerve processes within the sensory epithelium. This structural regeneration is accompanied by a significant recovery of auditory function and thus allows the animal to regain its hearing ability. This hair cell regeneration is presumably quite beneficial to birds, whose primary means of communication is based on vocalizations and the ability to hear and comprehend them. The prevalence of hearing loss in our society and the isolating impact it has on affected individuals makes the potential for finding ways to induce a similar hair cell regeneration in humans a very tempting goal. Studies of hair cell regeneration over the last 12 years have focused on the mechanisms that regulate the process and how they could be controlled. This review will examine the structural events involved in regenerating hair cells in the avian cochlea after sound damage and aminoglycoside treatment. It will define how hair cells and nerve endings are lost and the tectorial membrane is damaged by the traumatizing stimuli and how the supporting cells and nerve fibers respond by producing new hair cells, a new tectorial membrane and new synaptic connections during recovery. Finally, it will focus on mechanisms that control the proliferation and transdifferentiation of supporting cells and the differentiation of new hair cells. This structural review is accompanied by a companion review that covers the fundamental issues concerning functional recovery in the avian cochlea associated with hair cell regeneration.