Age-Related Hearing Loss Begins with Gain, Not Silence: Physiological Compensation in Dorsal Cochlear Nucleus Fusiform Cells During Auditory Aging

Age-related hearing loss (ARHL) is the most common cause of sensorineural hearing loss. The cochlear nucleus, the first central auditory structure to receive input from the cochlea, has been shown to be disrupted by ARHL. Fusiform cells (FC), the principal output cell of the dorsal cochlear nucleus (DCN), mature physiologically during hearing onset. Specifically, FCs increase in rate of action potential (AP) rise and decay, stabilizing by postnatal day 14 (P14) in mice. However, whether FC intrinsic electrophysiological properties or morphological characteristics continue to change throughout the life of mice, and how they change due to ARHL, is unknown. We characterized electrophysiological and morphological properties of FCs from CBA/CaJ mice at five stages of age: preweaning (P15-20), pubescent (P21-49), young adult (P50-179), mature adult (P180-364), and old adult (P550-578). Old adult mice had smaller auditory brainstem evoked response amplitudes and loss of hair cells, indicative of ARHL onset. We observed no change in FC membrane properties with age. FCs from the old adult group had faster action potential (AP) repolarization rates, shorter AP half-widths, and elevated firing rates. Morphologically, there was no change in FC soma shape or size. However, significant pruning of basal dendrites occurred between preweaning and pubescent ages. Interestingly, FCs alter their spatial organization of basal dendrities with age, likely due to the loss of auditory nerve input. Together, these results suggest that FC physiology and morphology are relatively stable post weaning and begin to exhibit intrinsic and structural compensation during the onset of ARHL.