Atg7-dependent autophagy is indispensable for mice spiral ganglion neurons.

Atg7-dependent autophagy is critical for the long-term maintenance of the post-mitotic cells, yet its role in spiral ganglion neurons (SGNs) remains incompletely defined. Here, we conditionally ablated Atg7 in SGNs by generating Bhlhe22Cre/+Atg7flox/flox mice and examined cellular p62 aggregates, ultrastructure, and auditory function at postnatal day (P)30 and P60. At P30, Atg7 was markedly reduced in SGNs. Immunofluorescence revealed progressive enlargement of p62-positive condensates from nano-scale at P30 to micron-scale by P60. Excess p62 activated the antioxidant transcription factor Nrf2. Transmission electron microscopy demonstrated progressive axonal degeneration, including vacuolated axoplasm, mitochondrial abnormalities, and disorganization of myelin lamellae with a characteristic wavy appearance. Functionally, ABR thresholds were preserved at P30 but became significantly elevated by P60 (approximately 30 dB on average), indicating age-dependent hearing loss. The amplitude and latency analysis of ABR waves implied that hearing loss may primarily attributed to autophagy-impaired SGNs rather than other auditory brain neurons of Bhlhe22 lineage. The postsynaptic GluR2 receptors, but not presynaptic CtBP2, dramatically decreased at P60. Together, these data show that Atg7-dependent autophagy is required to preserve SGN over time, thereby maintaining the auditory function.