Figure 1. Ouabain eliminated > 95% of Type-I SGN synapses and most indications of hearing according to brainstem activity, yet tone audibility remained intact.

(a) Cochlear histopathology from a control (top) and ouabain-treated (bottom) adult mouse. Juxtaposition of IHC presynaptic ribbons (red) and glutamate postsynaptic receptors (green) indicate a functional synapse (combined red and green arrow). Orphaned ribbons and receptors are indicated by purely red or green arrows, respectively. IHCs are outlined in white. (b) Synaptic counts per IHC across the cochlear frequency axis (Intact ear, black line: n = 4; Ouabain ear, red line: n = 13; F = 377.7, p < 0.01, repeated measures ANOVA. Error bars are mean +/− SEM). (c) DPOAE thresholds indicated that hair cell amplification was intact and functional (Intact ear vs ouabain ear, n = 8; F = 1.1, p = 0.31, repeated measures ANOVA). (d,e) Auditory brainstem response (ABR) wave 1b (e, inset) thresholds (d, n = 8, F = 68.8, p < 0.01, repeated measures ANOVA) and amplitudes (e, n = 8, F = 28.9, p < 0.01) at 8 kHz reflect the massive loss of nerve fibers. (f–g) Auditory startle response (f) and tone detection (g) are shown for the same mice (a–e) also using 8 kHz tones. The startle response is eliminated in all mice after ouabain (n = 6, F = 11.1, p < 0.01, repeated measures ANOVA) despite normal tone sensitivity in 3/4 mice. (g, right). In a different cohort of mice, detection probability at 80–90 dB SPL through the denervated ear is tested with the control ear deafened (red, n = 6) or in mice with 100% elimination of type-I SGNs in both ears (blue, n = 2). Errorbars are mean +/− SEM. (h) 8 kHz ABR w1b amplitude (top) and 8 kHz tone detection probability at 80–90 dB (bottom) is compared to synaptic innervation at the 8kHz region of the cochlea (individual mice are distinguished by circle color).