Functional Recovery of Hearing following AMPA-Induced Reversible Disruption of Hair Cell Afferent Synapses in the Avian Inner Ear

Abstract

Hair cells in the avian inner ear can regenerate after acoustic trauma or ototoxic insult, and significant functional recovery from hearing loss occurs. However, small residual deficits remain, possibly as a result of incomplete reestablishment of the hair cell neural synaptic contacts. The aim of the present study was to determine if intracochlear application of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), an excitotoxic glutamate agonist, causes reversible disruption of hair cell neural contacts in the bird, and to what extent functional recovery occurs if synaptic contacts are reestablished. Compound action potential (CAP) responses to tone bursts were recorded to determine hearing thresholds during a recovery period of up to 4 months. Subsequently, the response properties of single auditory nerve fibers were analyzed in the same animals. Instillation of AMPA into the perilymph of the scala tympani led to immediate abolition of CAP thresholds. Partial recovery occurred over a period of 2–3 weeks, without further improvement of thresholds thereafter. High-frequency thresholds did not reach control values even after 3–4 months of recovery. Single-ganglion cell response properties, obtained 3–4 months after AMPA treatment, showed elevated thresholds at the fiber’s characteristic frequency (CF) for units with CF above 0.3 kHz. Sharpness of tuning (Q_{10 dB}) was reduced in units with CF above 0.4 kHz. The spontaneous firing rate was higher in units with CF above 0.18 kHz. The maximum sound-evoked discharge rate was also increased. Transmission electron micrographs of the basilar papilla showed that, following AMPA treatment, the nerve endings went through a sequence of swelling, degeneration and recovery over a period of 3–7 days. The process of neosynaptogenesis was completed 14 days after exposure. The present findings are strong evidence for a role of glutamate or a related excitatory amino acid as the afferent transmitter in the avian inner ear. In addition they show that functional recovery after disruption and regeneration of hair cell neural synapses, without apparent damage to the hair cells, is incomplete.

Glutamate agonist causes irreversible degeneration of inner hair cells

“…Reng et al [11] showed that AMPA induced reversible hearing impairment in the avian ear. Similar findings were noted by Le Prell et al [12], who mentioned that the hearing deficit caused by chronic application of AMPA recovered within several days after cessation of the application.…”

Transient Ca2+‐permeable AMPA receptors in postnatal rat primary auditory neurons

“…High levels of GluR2 expression would thus limit Ca 2+ entry and its deleterious consequences (Pellegrini‐Giampietro et al ., 1997; Feldmeyer et al ., 1999; Oguro et al ., 1999; Van Damme et al ., 2002; Friedman et al ., 2003), in particular in view of the high transmission rates in primary auditory neurons necessary for coding of the temporal information contained in sounds (Trussell, 1997). Interestingly, excitotoxicity in the adult cochlea does not result in massive primary auditory neuron death (Puel et al ., 1995, 1998; Zheng et al ., 1997; Reng et al ., 2001).…”

Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

“…The discovery that hair cells of the avian basilar papilla (BP), the functional equivalent of the mammalian organ of Corti, are regenerated after preexisting hair cells have been destroyed (Corwin and Cotanche 1988;Ryals and Rubel 1988;Warchol and Corwin 1996) has stimulated much interest in the possibility of hair cell regeneration therapy in mammals (Staecker and Van De Water 1998). The continuous formation of cochlear sensory epithelial cells with and without insult to the auditory system has also been demonstrated in the lower vertebrate inner ear, but not in mammals (Cotanche and Lee 1994;Stone and Rubel 2000;Reng et al 2001).…”