Hair Cell Regeneration Reveals Central Nervous System Plasticity in the Avian Brain

Two separate lines of behavioral research are reported here. Both sets of experiments were begun to examine whether hair cell regeneration in the avian inner ear could support the recovery of complex behaviors. However, both have gone on to reveal new information about the important role of peripheral input for central nervous system plasticity. A series of experiments examined the recovery of vestibular reflexes in hatchling chickens following aminoglycoside ototoxicity to the vestibular epithelium. Treatment with aminoglycosides results in hair cell loss and loss of both the vestibulo-ocular reflex (VOR) and the vestibulo-colic reflex (VCR). We found a good general correspondence between hair cell regeneration and recovery of both the VOR and the VCR. When animals were maintained under normal illumination, recovery of both reflexes was generally complete in 4 weeks. However, when the animals were maintained in illumination provided by a strobe light flashing at 2.5 Hz for 4 weeks, this correlation broke down. Hair cells recovered normally, as did the VCR, but the VOR did not recover. Remarkably, placing the animals in normal illumination for only 48 hours after 4 weeks of strobe rearing resulted in full recovery of the VOR. In another series of experiments, we examined the deterioration and recovery of adult Bengalese finch songs after hair cell loss and during hair cell regeneration. Bengalese finches learn their individual songs only as juveniles and sing stereotyped, stable songs as adults. After deafening by a combination of aminoglycoside and high-intensity noise exposures, the songs of individual birds deteriorated in both syllable order and the structure of individual syllables. Remarkably, because hearing was restored by regeneration of hair cells, songs returned to their original structure in 4 weeks. These results indicate that adult birds retain "blueprints" of their own songs. Following initial song recovery, two of seven adult birds that were housed with other singing birds produced new syllables that mimicked their cage mate's songs. The new syllables were incorporated into the recovered songs, suggesting that hair cell loss and regeneration unmasked neural plasticity not normally seen in the mature avian forebrain. Both sets of experiments show that regenerated hair cells can support the recovery of complex behavior. The increases in behavioral plasticity observed during and after hair cell regeneration suggest that hair cell loss and regeneration either stimulate or reveal the plasticity of neural circuits controlling behavior normally not observed in adult birds.