부산대학교 도서관

Noise-induced excitotoxicity is thought to depend on glutamate. However, the excitotoxic mechanisms are unknown, and the necessity of glutamate for synapse loss or regeneration is unclear. Despite absence of glutamatergic transmission from cochlear inner hair cells in mice lacking the vesicular glutamate transporter-3 (Vglut3K0), at 9-11 weeks, approximately half the number of synapses found in Vglut3n 7 were maintained as postsynaptic AMPA receptors juxtaposed with presynaptic ribbons and voltage-gated calcium channels (Cav1.3). Synapses were larger in Vglut3K(> than Vglut3wr. In Vglut3 " 1 and Vglut3+/- mice, 8-16 kHz octave-band noise exposure at 100 dB sound pressure level caused a threshold shift (--40 dB) and a loss of synapses (>50%) at 24 h after exposure. Hearing threshold and synapse number partially recovered by 2 weeks after exposure as ribbons became larger, whereas recovery was significantly better in Vglut3n Noise exposure at 94 dB sound pressure level caused auditory threshold shifts that fully recovered in 2 weeks, whereas suprathreshold hearing recovered faster in Vglut3+/- than Vglut3+/-. These results, from mice of both sexes, suggest that spontaneous repair of synapses after noise depends on the level of Vglut3 protein or the level of glutamate release during the recovery period. Noise-induced loss of presynaptic ribbons or postsynaptic AMPA receptors was not observed in Vglut3K0, demonstrating its dependence on vesicular glutamate release. In Vglut3wT and Vglut3+/- noise exposure caused unpairing of presynaptic ribbons and presynaptic Cavl .3, but not in Vglut3ko where Cav1.3 remained clustered with ribbons at presynaptic active zones. These results suggest that, without glutamate release, noise-induced presynaptic Ca2+ influx was insufficient to disassemble the active zone. However, synapse volume increased by 2 weeks after exposure in Vglut3K0, suggesting glutamate-independent mechanisms. [ABSTRACT FROM AUTHOR]